Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas.
AMP-Activated Protein Kinases
/ metabolism
Alcohol Drinking
Antineoplastic Agents
/ pharmacology
Autophagosomes
/ metabolism
Autophagy
/ drug effects
Biomarkers
/ metabolism
Esophageal Neoplasms
/ drug therapy
Esophageal Squamous Cell Carcinoma
/ drug therapy
Genetic Predisposition to Disease
Humans
Lysosomes
/ metabolism
Mouth Neoplasms
/ drug therapy
Prognosis
Radiotherapy
/ methods
Signal Transduction
Tobacco Products
Virus Diseases
/ complications
autophagy
autophagy modulators
biomarkers
esophageal squamous cell carcinoma
exosomes
oral squamous cell carcinoma
targeted therapy
Journal
Medicinal research reviews
ISSN: 1098-1128
Titre abrégé: Med Res Rev
Pays: United States
ID NLM: 8103150
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
17
07
2019
revised:
16
10
2019
accepted:
08
11
2019
pubmed:
20
11
2019
medline:
28
9
2021
entrez:
20
11
2019
Statut:
ppublish
Résumé
Oral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC) exhibit a survival rate of less than 60% and 40%, respectively. Late-stage diagnosis and lack of effective treatment strategies make both OSCC and ESCC a significant health burden. Autophagy, a lysosome-dependent catabolic process, involves the degradation of intracellular components to maintain cell homeostasis. Targeting autophagy has been highlighted as a feasible therapeutic strategy with clinical utility in cancer treatment, although its associated regulatory mechanisms remain elusive. The detection of relevant biomarkers in biological fluids has been anticipated to facilitate early diagnosis and/or prognosis for these tumors. In this context, recent studies have indicated the presence of specific proteins and small RNAs, detectable in circulating plasma and serum, as biomarkers. Interestingly, the interplay between biomarkers (eg, exosomal microRNAs) and autophagic processes could be exploited in the quest for targeted and more effective therapies for OSCC and ESCC. In this review, we give an overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC. Additionally, we provide a viewpoint on the state of the art and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery for the treatment of OSCC and ESCC.
Substances chimiques
Antineoplastic Agents
0
Biomarkers
0
AMP-Activated Protein Kinases
EC 2.7.11.31
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1002-1060Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
Cheng MF, Lin SR, Tseng FJ, et al. The autophagic inhibition oral squamous cell carcinoma cancer growth of 16-hydroxy-cleroda-3,14-dine-15,16-olide. Oncotarget. 2017;8(45):78379-78396.
Ohashi S, Miyamoto S, Kikuchi O, Goto T, Amanuma Y, Muto M. Recent advances from basic and clinical studies of esophageal squamous cell carcinoma. Gastroenterology. 2015;149(7):1700-1715.
Joshi P, Dutta S, Chaturvedi P, Nair S. Head and neck cancers in developing countries. Rambam Maimonides Med J. 2014;5(2):e0009.
Sinevici N, O'Sullivan J. Oral cancer: deregulated molecular events and their use as biomarkers. Oral Oncol. 2016;61:12-18.
Lin DC, Wang MR, Koeffler HP. Genomic and epigenomic aberrations in esophageal squamous cell carcinoma and implications for patients. Gastroenterology. 2018;154(2):374-389.
Hema Shree K, Ramani P, Sherlin H, Sukumaran G, Jeyaraj G, Don KR. Saliva as a diagnostic tool in oral squamous cell carcinoma: a systematic review with meta analysis. Pathol Oncol Res. 2019;25:447.
Irimie AI, Braicu C, Zanoaga O, et al. Epigallocatechin-3-gallate suppresses cell proliferation and promotes apoptosis and autophagy in oral cancer SSC-4 cells. Onco Targets Ther. 2015;20(8):461-470.
Martin JL, Wolanin A, Lerner I. Oral cancer screening. Reducing fear using salivary diagnostics. Dent Today. 2016;35(5):12-14.
Soodan KS, Priyadarshni P, Kumar MSS. Systematic review on oral cancer. EC Dent Sci. 2018;17:116-119.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin. 2018;68(6):394-424.
Robert BM, Dakshinamoorthy M, Ganapathyagraharam Ramamoorthy B, et al. Predicting tumor sensitivity to chemotherapeutic drugs in oral squamous cell carcinoma patients. Sci Rep. 2018;8(1):15545.
Duong C, Hicks RJ. Imaging of esophageal squamous cell carcinoma. Gastroenterology. 2018;154(2):23-26.
Associazione Italiana di Oncologia Medica & Associazione Italiana dei Registri Tumori. I Numeri del Cancro in Italia 2018-I dati regionali. Via Malta 12/B - 25124 Brescia: Aiom; 2018.
Awan KH, Patil S. Association of smokeless tobacco with oral cancer-Evidence from the South Asian studies: A systematic review. J Coll Physicians Surg Pak. 2016;26(9):775-780.
Sinha DN, Abdulkader RS, Gupta PC. Smokeless tobacco-associated cancers: A systematic review and meta-analysis of Indian studies. Int J cancer. 2016;138(6):1368-1379.
Wang QL, Xie SH, Li WT, Lagergren J. Smoking cessation and risk of esophageal cancer by histological type: systematic review and meta-analysis. J Natl Cancer Inst. 2017;109(12):1-10.
Warnakulasuriya S, Dietrich T, Bornstein MM, et al. Oral health risks of tobacco use and effects of cessation. Int Dent J. 2010;60(1):7-30.
Bosetti C, Gallus S, Peto R, et al. Tobacco smoking, smoking cessation, and cumulative risk of upper aerodigestive tract cancers. Am J Epidemiol. 2008;167(4):468-473.
Rosenquist K. Risk factors in oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden. Swed Dent J Suppl. 2005;179:1-66.
Samatha Y, Sai Sankar AJ, Ganapathy KS, Srinivas K, Ankineedu D, Subhashini Choudary AL. Clinicopathologic evaluation of lesions associated with tobacco usage. J Contemp Dent Pract. 2014;15(4):466-472.
Al-Attas SA, Ibrahim SS, Amer HA, Darwish ZE, Hassan MH. Prevalence of potentially malignant oral mucosal lesions among tobacco users in Jeddah, Saudi Arabia. Asian Pac J Cancer Prevent. 2014;15(2):757-762.
Chandra P, Govindraju P. Prevalence of oral mucosal lesions among tobacco users. Oral Health Prev Dent. 2012;10(2):149-153.
Vargas-Ferreira F, Nedel F, Etges A, Gomes A, Furuse C, Tarquinio S. Etiologic factors associated with oral squamous cell carcinoma in non-smokers and non-alcoholic drinkers: a brief approach. Braz Dent J. 2012;23(5):586-590.
Warnakulasuriya K, Ralhan R. Clinical, pathological, cellular and molecular lesions caused by oral smokeless tobacco-a review. J Oral Pathol Med. 2007;36(2):63-77.
Lubin JH, Purdue M, Kelsey K, et al. Total exposure and exposure rate effects for alcohol and smoking and risk of head and neck cancer: a pooled analysis of case-control studies. Am J Epidemiol. 2009;170(8):937-947.
Abnet CC, Arnold M, Wei W-Q. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology. 2018;154(2):360-373.
Johnson N. Tobacco use and oral cancer: a global perspective. J Dent Educ. 1991;65(4):328-339.
Campisi G, Panzarella V, Giuliani M, et al. Human papillomavirus: Its identikit and controversial role in oral oncogenesis, premalignant and malignant lesions. Int J Oncol. 2007;30(4):813-823.
Termine N, Panzarella V, Falaschini S, et al. HPV in oral squamous cell carcinoma vs head and neck squamous cell carcinoma biopsies: a meta-analysis (1988-2007). Ann Oncol. 2008;19(10):1681-1690.
Siebers TJH, Merkx MAW, Slootweg PJ, Melchers WJG, Van Cleef P, de Wilde PCM. No high-risk HPV detected in SCC of the oral tongue in the absolute absence of tobacco and alcohol-a case study of seven patients. Oral Maxillofac Surg. 2008;12(4):185-188.
Ali J, Sabiha B, Jan HU, Haider SA, Khan AA, Ali SS. Genetic etiology of oral cancer. Oral Oncology. 2017;70:23-28.
Xie SH, Lagergren J. Risk factors for oesophageal cancer. Best Pract Res Clin Gastroenterol. 2018;36-37:3-8.
Gupta B, Bray F, Kumar N, Johnson NW. Associations between oral hygiene habits, diet, tobacco and alcohol and risk of oral cancer: A case-control study from India. Cancer Epidemiology. 2017;51(September):7-14.
Porter S, Gueiros LA, Leão JC, Fedele S. Risk factors and etiopathogenesis of potentially premalignant oral epithelial lesions. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125(6):603-611.
Xu XC. Risk factors and gene expression in esophageal cancer. Methods Mol Biol. 2010;471(2):8-12.
Gharat SA, Momin M, Bhavsar C. Oral squamous cell carcinoma: current treatment strategies and nanotechnology-based approaches for prevention and therapy. Crit Rev Ther Drug Carrier Syst. 2016;33(4):363-400.
Smyth EC, Lagergren J, Fitzgerald RC, et al. Oesophageal cancer. Nat Rev Dis Primers. 2017;3:17048.
Noordzij IC, Curvers WL, Schoon EJ. Endoscopic resection for early esophageal carcinoma. J Thorac Dis. 2019;11(I):S713-S722.
Lagergren J, Smyth E, Cunningham D, Lagergren P. Oesophageal cancer. Lancet. 2017;390:2383-2396.
Pendleton KP, Grandis JR. Cisplatin-based chemotherapy options for recurrent and/or metastatic squamous cell cancer of the head and neck. Clin Med Insights Ther. 2013;5:103-116.
Freeman K, Connock M, Cummins E, et al. Fluorouracil plasma monitoring: systematic review and economic evaluation of the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion. Health Technol Assess. 2015;19(91):1-322.
Chakraborty S, Geetha M, Sujith KM, Biji MS, Sateeshan B. Palliative low dose fortnightly methotrexate in oral cancers: experience at a rural cancer centre from India. South Asian J Cancer. 2014;3(3):166.
Ledwitch K, Ogburn R, Cox J, et al. Taxol: efficacy against oral squamous cell carcinoma. Mini-Rev Med Chem. 2013;13(4):509-521.
Caponigro F, Longo F, Perri F, Ionna F. Docetaxel in the management of head and neck cancer. Anti-Cancer Drugs. 2009;20(8):639-645.
Eder-Czembirek C, Rechinger S, Kornek G, Selzer E, Seemann R. Experience in intra-arterial chemotherapy using two protocols for the treatment of OSCC over two decades at the University Hospital Vienna. Clinics. 2018;73:73.
Busch C-J, Tribius S, Schafhausen P, Knecht R. The current role of systemic chemotherapy in the primary treatment of head and neck cancer. Cancer Treat Rev. 2015;41(3):217-221.
Lau A, Li KY, Yang WF, Su YX. Induction chemotherapy for squamous cell carcinomas of the oral cavity: a cumulative meta-analysis. Oral Oncol. 2016;61:104-114.
Klevebro F, Ekman S, Nilsson M. Current trends in multimodality treatment of esophageal and gastroesophageal junction cancer: review article. Surg Oncol. 2017;26(3):290-295.
Wang XJ, Yu J, Wong SH, et al. A novel crosstalk between two major protein degradation systems. Autophagy. 2013;9(10):1500-1508.
Ding WX, Yin XM. Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem. 2012;393(7):547-564.
Kaushik S, Cuervo AM. Chaperone-mediated autophagy: a unique way to enter the lysosome world. Trends Cell Biol. 2012;22(8):407-417.
EVOLVE Trial Investigators, Chertow GM, Block GA. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012;367(26):2482-2494.
Macintosh RL, Ryan KM. Autophagy in tumour cell death. Semin Cancer Biol. 2013;23(5):344-351.
Yun CW, Lee SH. The roles of autophagy in cancer. Int J Mol Sci. 2018;19(11):3466.
He S, Li Q, Jiang X, et al. Design of small molecule autophagy modulators: a promising druggable strategy. J Med Chem. 2018;61(11):4656-4687.
Folkerts H, Hilgendorf S, Vellenga E, Bremer E, Wiersma VR. The multifaceted role of autophagy in cancer and the microenvironment. Med Res Rev. 2019;39(2):517-560.
Galluzzi L, Baehrecke EH, Ballabio A, et al. Molecular definitions of autophagy and related processes. EMBO J. 2017;36(13):1811-1836.
Rostislavleva K, Soler N, Ohashi Y, et al. Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes. Science. 2015;350(6257):aac7365-aac7365.
Wong PM, Feng Y, Wang J, Shi R, Jiang X. Regulation of autophagy by coordinated action of mTORC1 and protein phosphatase 2A. Nat Commun. 2015;6:8048.
Egan DF, Shackelford DB, Mihaylova MM, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011;331(6016):456-461.
Pattingre S, Tassa A, Qu X, et al. Bcl-2 antiapoptotic proteins inhibit beclin 1-dependent autophagy. Cell. 2005;122(6):927-939.
Tai WT, Shiau CW, Chen HL, et al. Mcl-1-dependent activation of beclin 1 mediates autophagic cell death induced by sorafenib and SC-59 in hepatocellular carcinoma cells. Cell Death Dis. 2013;4(2):e485-e485.
Takahashi Y, Coppola D, Matsushita N, et al. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol. 2007;9(10):1142-1151.
Strappazzon F, Vietri-Rudan M, Campello S, et al. Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO J. 2011;30(7):1195-1208.
Molejon MI, Ropolo A, Re AL, Boggio V, Vaccaro MI. The VMP1-beclin 1 interaction regulates autophagy induction. Sci Rep. 2013;3:1055.
Walczak M, Martens S. Dissecting the role of the Atg12-Atg5-Atg16 complex during autophagosome formation. Autophagy. 2013;9(3):424-425.
Pankiv S, Clausen TH, Lamark T, et al. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem. 2007;282(33):24131-24145.
Kast DJ, Dominguez R. The cytoskeleton-autophagy connection. Current Biology. 2017;27(8):R318-R326.
Huynh KK, Eskelinen EL, Scott CC, Malevanets A, Saftig P, Grinstein S. LAMP proteins are required for fusion of lysosomes with phagosomes. EMBO J. 2007;26(2):313-324.
Qu X, Yu J, Bhagat G, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest. 2003;112(12):1809-1820.
Coppola D, Khalil F, Eschrich SA, Boulware D, Yeatman T, Wang H-G. Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma. Cancer. 2008;113(10):2665-2670.
Takahashi Y, Coppola D, Matsushita N, et al. Bif-1 interacts with beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol. 2007;9(10):1142-1151.
Kang MR, Kim MS, Oh JE, et al. Frameshift mutations of autophagy-related genes ATG2B, ATG5, ATG9B and ATG12 in gastric and colorectal cancers with microsatellite instability. J Pathol. 2009;217(5):702-706.
He S, Zhao Z, Yang Y, et al. Truncating mutation in the autophagy gene UVRAG confers oncogenic properties and chemosensitivity in colorectal cancers. Nat Commun. 2015;6:7839.
Liang XH, Jackson S, Seaman M, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999;402(6762):672-676.
Guo JY, Chen HY, Mathew R, et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev. 2011;25(5):460-470.
Kubisch J, Türei D, Földvári-Nagy L, et al. Complex regulation of autophagy in cancer-integrated approaches to discover the networks that hold a double-edged sword. Semin Cancer Biol. 2013;23(4):252-261.
Meijer AJ, Codogno P. Autophagy: regulation and role in disease. Crit Rev Clin Lab Sci. 2009;46(4):210-240.
Lorin S, Hamaï A, Mehrpour M, Codogno P. Autophagy regulation and its role in cancer. Semin Cancer Biol. 2013;23(5):361-379.
Aoki M, Fujishita T. Oncogenic Roles of the PI3K/AKT/mTOR Axis. Curr Topics Microbiol Immunol. 2017;407:153-189.
Cancer Genome Atlas. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517:576-582.
Barakat DJ, Friedman AD. Autophagy is required for PTEN-loss driven prostate cancer. Transl Cancer Res. 2016;5:S725-S729.
Wright TJ, McKee C, Birch-Machin MA, Ellis R, Armstrong JL, Lovat PE. Increasing the therapeutic efficacy of docetaxel for cutaneous squamous cell carcinoma through the combined inhibition of phosphatidylinositol 3-kinase/AKT signalling and autophagy. Clin Exp Dermatol. 2013;38(4):421-423.
Trocoli A, Djavaheri-Mergny M. The complex interplay between autophagy and NF-κB signaling pathways in cancer cells. Am J Cancer Res. 2011;1(5):629-649.
Schmukler E, Kloog Y, Pinkas-Kramarski R. Ras and autophagy in cancer development and therapy. Oncotarget. 2014;5(3):577.
Furuta S, Hidaka E, Ogata A, Yokota S, Kamata T. Ras is involved in the negative control of autophagy through the class I PI3-kinase. Oncogene. 2004;23(22):3898-3904.
Karnoub AE, Weinberg RA. Ras oncogenes: split personalities. Nat Rev Mol Cell Biol. 2008;9(7):517-531.
Scherz-Shouval R, Weidberg H, Gonen C, Wilder S, Elazar Z, Oren M. p53-dependent regulation of autophagy protein LC3 supports cancer cell survival under prolonged starvation. Proc Natl Acad Sci USA. 2010;107(43):18511-18516.
Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer. Nat Rev Cancer. 2017;17(9):528-542.
Morgan MJ, Gamez G, Menke C, et al. Regulation of autophagy and chloroquine sensitivity by oncogenic RAS in vitro is context-dependent. Autophagy. 2014;10(10):1814-1826.
Liu B, Bao JK, Yang JM, Cheng Y. Targeting autophagic pathways for cancer drug discovery. Chin J Cancer. 2013;32(3):113-120.
Rosenfeldt MT, O'Prey J, Morton JP, et al. p53 status determines the role of autophagy in pancreatic tumour development. Nature. 2013;504(7479):296-300.
Li W, Saud SM, Young MR, Chen G, Hua B. Targeting AMPK for cancer prevention and treatment. Oncotarget. 2015;6(10):7365-7378.
Jiang X, Tan HY, Teng S, Chan YT, Wang D, Wang N. The role of AMP-Activated protein kinase as a potential target of treatment of hepatocellular carcinoma. Cancers (Basel). 2019;11(5):647.
Liu C, Sun L, Yang J, et al. FSIP1 regulates autophagy in breast cancer. Proc Natl Acad Sci. 2018;115(51):13075-13080.
You L, Wang Z, Li H, et al. The role of STAT3 in autophagy. Autophagy. 2015;11(5):729-739.
Maycotte P, Jones KL, Goodall ML, Thorburn J, Thorburn A. Autophagy supports breast cancer stem cell maintenance by regulating IL6 secretion. Mol Cancer Res. 2015;13(4):651-658.
Yoshii SR, Mizushima N. Monitoring and measuring. Int J Mol Sci. 2017;18:1-13.
Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12(1):1-222.
Solitro AR, Mackeigan JP. Leaving the lysosome behind: novel developments in autophagy inhibition. Future Med Chem. 2016;8(1):73-86.
Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J, Pedraza-Chaverri J. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal. 2014;26(12):2694-2701.
O'Farrell F, Rusten TE, Stenmark H. Phosphoinositide 3-kinases as accelerators and brakes of autophagy. FEBS J. 2013;280(24):6322-6337.
Vinod V, Padmakrishnan CJ, Vijayan B, Gopala S. ‘How can I halt thee?’ The puzzles involved in autophagic inhibition. Pharmacol Res. 2014;82:1-8.
Wu Y, Wang X, Guo H, et al. Synthesis and screening of 3-MA derivatives for autophagy inhibitors. Autophagy. 2013;9(4):595-603.
Powis G, Bonjouklian R, Berggren MM, et al. Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase. Cancer Res. 1994;54(9):2419-2423.
Kim J, Kim YC, Fang C, et al. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell. 2013;152(1):290-303.
Kim TM, Baek JH, Kim JH, Oh MS, Kim J. Development of in vitro PIK3C3/VPS34 complex protein assay for autophagy-specific inhibitor screening. Anal Biochem. 2015;480:21-27.
Morris DH, Yip CK, Shi Y, Chait BT, Wang QJ. Beclin 1-Vps34 complex architecture: understanding the nuts and bolts of therapeutic targets. Front Biol. 2015;10(5):398-426.
Liu J, Xia H, Kim M, et al. Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell. 2011;147(1):223-234.
Malik SA, Orhon I, Morselli E, et al. BH3 mimetics activate multiple pro-autophagic pathways. Oncogene. 2011;30(37):3918-3929.
Miller S, Tavshanjian B, Oleksy A, et al. Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34. Science. 2010;327(5973):1638-1642.
Honda A, Harrington E, Cornella-Taracido I, et al. Potent, selective, and orally bioavailable inhibitors of VPS34 provide chemical tools to modulate autophagy in vivo. ACS Med Chem Lett. 2016;7(1):72-76.
Ronan B, Flamand O, Vescovi L, et al. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol. 2014;10:1013-1019.
Feldman ME, Apsel B, Uotila A, et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLOS Biol. 2009;7(2):e1000038.
Pike KG, Malagu K, Hummersone MG, et al. Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014. Bioorg Med Chem Lett. 2013;23(5):1212-1216.
Wander SA, Hennessy BT, Slingerland JM. Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy. J Clin Invest. 2011;121(4):1231-1241.
Button RW, Vincent JH, Strang CJ, Luo S. Dual PI-3 kinase/mTOR inhibition impairs autophagy flux and induces cell death independent of apoptosis and necroptosis. Oncotarget. 2016;7(5):5157-5175.
D'Amato V, Rosa R, D'Amato C, et al. The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models. Br J Cancer. 2014;110:2887-2895.
Ji Y, Di W, Yang Q, Lu Z, Cai W, Wu J. Inhibition of autophagy increases proliferation inhibition and apoptosis induced by the PI3K/mTOR inhibitor NVP-BEZ235 in breast cancer cells. Clin Lab. 2015;61(8):1043-1051.
Shi WY, Xiao D, Wang L, et al. Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy. Cell Death Dis. 2012;3(3):e275-e275.
Zhao M, Klionsky DJ. AMPK-Dependent Phosphorylation of ULK1 Induces Autophagy. Cell Metabol. 2011;13(2):119-120.
Ben Sahra I, Regazzetti C, Robert G, et al. Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res. 2011;71(13):4366-4372.
Pang T, Zhang ZS, Gu M, et al. Small molecule antagonizes autoinhibition and activates AMP-activated protein kinase in cells. J Biol Chem. 2008;283(23):16051-16060.
Lee KH, Hsu EC, Guh JH, et al. Targeting energy metabolic and oncogenic signaling pathways in triple-negative breast cancer by a novel adenosine monophosphate-activated protein kinase (AMPK) activator. J Biol Chem. 2011;286(45):39247-39258.
Chan EYW, Kir S, Tooze SA. siRNA screening of the kinome identifies ULK1 as a multidomain modulator of autophagy. J Biol Chem. 2007;282(35):25464-25474.
Chen Y, He J, Tian M, et al. UNC51-like kinase 1, autophagic regulator and cancer therapeutic target. Cell Prolif. 2014;47(6):494-505.
Jiang S, Li Y, Zhu Y-H, et al. Intensive expression of UNC-51-like kinase 1 is a novel biomarker of poor prognosis in patients with esophageal squamous cell carcinoma. Cancer Sci. 2011;102(8):1568-1575.
Tang J, Deng R, Luo R-Z, et al. Low expression of ULK1 is associated with operable breast cancer progression and is an adverse prognostic marker of survival for patients. Breast Cancer Res Treat. 2012;134(2):549-560.
Xu H, Yu H, Zhang X, et al. UNC51-like kinase 1 as a potential prognostic biomarker for hepatocellular carcinoma. Int J Clin Exp Pathol. 2013;6(4):711-717.
Li TY, Sun Y, Liang Y, et al. ULK1/2 constitute a bifurcate node controlling glucose metabolic fluxes in addition to autophagy. Mol Cell. 2016;62(3):359-370.
Egan DF, Chun MGH, Vamos M, et al. Small molecule inhibition of the autophagy kinase ULK1 and identification of ULK1 substrates. Mol Cell. 2015;59(2):285-297.
Lazarus MB, Novotny CJ, Shokat KM. Structure of the human autophagy initiating kinase ULK1 in complex with potent inhibitors. ACS Chem Biol. 2015;10(1):257-261.
Petherick KJ, Conway OJL, Mpamhanga C, et al. Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy. J Biol Chem. 2015;290(18):11376-11383.
Zhang L, Fu L, Zhang S, et al. Discovery of a small molecule targeting ULK1-modulated cell death of triple negative breast cancer in vitro and in vivo. Chem Sci. 2017;8(4):2687-2701.
Fernández ÁF, López-Otín C. The functional and pathologic relevance of autophagy proteases. J Clin Invest. 2015;125(1):33-41.
Li M, Hou Y, Wang J, Chen X, Shao ZM, Yin XM. Kinetics comparisons of mammalian Atg4 homologues indicate selective preferences toward diverse Atg8 substrates. J Biol Chem. 2011;286(9):7327-7338.
Tran E, Chow A, Goda T, et al. Context-dependent role of ATG4B as target for autophagy inhibition in prostate cancer therapy. Biochem Biophys Res Commun. 2013;441(4):726-731.
Rothe K, Lin H, Lin KBL, et al. The core autophagy protein ATG4B is a potential biomarker and therapeutic target in CML stem/progenitor cells. Blood. 2014;123(23):3622-3634.
Satoo K, Noda NN, Kumeta H, et al. The structure of Atg4B-LC3 complex reveals the mechanism of LC3 processing and delipidation during autophagy. EMBO J. 2009;28(9):1341-1350.
Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F. Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy. J Biol Chem. 2005;280(48):40058-40065.
Akin D, Wang SK, Habibzadegah-Tari P, et al. A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors. Autophagy. 2014;10(11):2021-2035.
Qiu Z, Kuhn B, Aebi J, et al. Discovery of fluoromethylketone-based peptidomimetics as covalent ATG4B (Autophagin-1) inhibitors. ACS Med Chem Lett. 2016;7(8):802-806.
Rojas-Puentes LL, Gonzalez-Pinedo M, Crismatt A, et al. Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases. Radiat Oncol. 2013;8:209.
Molenaar RJ, Coelen RJ, Khurshed M, et al. Study protocol of a phase IB/II clinical trial of metformin and chloroquine in patients with IDH1-mutated or IDH2-mutated solid tumours. BMJ Open. 2017;7(6):e014961.
Sotelo J, Briceño E, López-González MA. Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2006;144:337.
Rangwala R, Leone R, Chang YC, et al. Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma. Autophagy. 2014;10(8):1369-1379.
Rangwala R, Chang YC, Hu J, et al. Combined MTOR and autophagy inhibition. Autophagy. 2014;10(8):1391-1402.
Vogl DT, Stadtmauer EA, Tan K-S, et al. Combined autophagy and proteasome inhibition. Autophagy. 2014;10(8):1380-1390.
Haas NB, Appleman LJ, Stein M, et al. Autophagy inhibition to augment mTOR inhibition: a Phase I/II trial of everolimus and hydroxychloroquine in patients with previously treated renal cell carcinoma. Clin Cancer Res. 2019;25(7):2080-2087.
Malhotra J, Jabbour S, Orlick M, et al. Modulation of autophagy with hydroxychloroquine in patients with advanced non-small cell lung cancer (NSCLC): a phase Ib study. J Clin Oncol. 2018;36(15_suppl):e21138-e21138.
Rosenfeld MR, Ye X, Supko JG, et al. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy. 2014;10(8):1359-1368.
McAfee Q, Zhang Z, Samanta A, et al. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc Natl Aca Sci USA. 2012;109(21):8253-8258.
Amaravadi RK, Winkler JD. Lys05: a new lysosomal autophagy inhibitor. Autophagy. 2012;8(9):1383-1384.
Fitzwalter BE, Towers CG, Sullivan KD, et al. Autophagy inhibition mediates apoptosis sensitization in cancer therapy by relieving FOXO3a turnover. Dev Cell. 2018;44(5):555-565.
Greene LM, Nolan DP, Regan-Komito D, Campiani G, Williams DC, Zisterer DM. Inhibition of late-stage autophagy synergistically enhances pyrrolo-1,5-benzoxazepine-6-induced apoptotic cell death in human colon cancer cells. Int J Oncol. 2013;43(3):927-935.
Li L, Xie W, Pan D, Chen H, Zhang L. Inhibition of autophagy by bafilomycin A1 promotes chemosensitivity of gastric cancer cells. Tumor Biol. 2016;37(1):653-659.
Han MW, Lee JC, Choi J-Y, et al. Autophagy inhibition can overcome radioresistance in breast cancer cells through suppression of TAK1 activation. Anticancer Res. 2014;34(3):1449-1455.
Yuan N, Song L, Zhang S, et al. Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia. Haematologica. 2015;100(3):345-356.
Liu Z, Liu J, Li L, et al. Inhibition of autophagy potentiated the antitumor effect of nedaplatin in cisplatin-resistant nasopharyngeal carcinoma cells. PLOS One. 2015;10(8):e0135236.
Xie Z, Xie Y, Xu Y, Zhou H, Xu W, Dong Q. Bafilomycin A1 inhibits autophagy and induces apoptosis in MG63 osteosarcoma cells. Mol Med Rep. 2014;10(2):1103-1107.
Pan Z, Xie Y, Bai J, Lin Q, Cui X, Zhang N. Bufalin suppresses colorectal cancer cell growth through promoting autophagy in vivo and in vitro. RSC Adv. 2018;8(68):38910-38918.
Leung ELH, Luo LX, Liu ZQ, et al. Inhibition of KRAS-dependent lung cancer cell growth by deltarasin: blockage of autophagy increases its cytotoxicity. Cell Death Dis. 2018;9(2):216.
Liu Z, He K, Ma Q. Autophagy inhibitor facilitates gefitinib sensitivity in vitro and in vivo by activating mitochondrial apoptosis in triple negative breast cancer. PLOS One. 2017;12(5):e0177694.
Li J, Yang D, Wang W, et al. Inhibition of autophagy by 3-MA enhances IL-24-induced apoptosis in human oral squamous cell carcinoma cells. J Exp Clin Cancer Res. 2015;34(1):97.
Tao H, Qian P, Lu J, Guo Y, Zhu H, Wang F. Autophagy inhibition enhances radiosensitivity of Eca-109 cells via the mitochondrial apoptosis pathway. Int J Oncol. 2018;52(6):1853-1862.
Yang W, Jiang C, Xia W, et al. Blocking autophagy flux promotes interferon-alpha-mediated apoptosis in head and neck squamous cell carcinoma. Cancer Letters. 2019;451:34-47.
Divac Rankov A, Ljujić M, Petrić M, Radojković D, Pešić M, Dinić J. Targeting autophagy to modulate cell survival: a comparative analysis in cancer, normal and embryonic cells. Histochem Cell Biol. 2017;148(5):529-544.
Ebrahimi S, Hosseini M, Shahidsales S, et al. Targeting the Akt/PI3K signaling pathway as a potential therapeutic strategy for the treatment of pancreatic cancer. Curr Med Chem. 2017;24:13.
Hashimoto D, Bläuer M, Hirota M, Ikonen NH, Sand J, Laukkarinen J. Autophagy is needed for the growth of pancreatic adenocarcinoma and has a cytoprotective effect against anticancer drugs. Eur J Cancer. 2014;50(7):1382-1390.
Liao Y, Guo Z, Xia X, et al. Inhibition of EGFR signaling with Spautin-1 represents a novel therapeutics for prostate cancer. J Exp Clin Cancer Res. 2019;38(1):157.
Liu J, Xia H, Kim M, et al. Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell. 2011;147(1):223-234.
Shao S, Li S, Qin Y, et al. Spautin-1, a novel autophagy inhibitor, enhances imatinib-induced apoptosis in chronic myeloid leukemia. Int J Oncol. 2014;44(5):1661-1668.
Kim KW, Moretti L, Mitchell LR, Jung DK, Lu B. Combined Bcl-2/mammalian target of rapamycin inhibition leads to enhanced radiosensitization via induction of apoptosis and autophagy in non-small cell lung tumor xenograft model. Clin Cancer Res. 2009;15(19):6096-6105.
Malik SA, Orhon I, Morselli E, et al. BH3 mimetics activate multiple pro-autophagic pathways. Oncogene. 2011;30(37):3918-3929.
Mecca C, Giambanco I, Bruscoli S, et al. PP242 counteracts glioblastoma cell proliferation, migration, invasiveness and stemness properties by inhibiting mTORC2/AKT. Front Cell Neurosci. 2018;12:99.
Seo SU, Woo SM, Lee H-S, Kim SH, Min K, Kwon TK. mTORC1/2 inhibitor and curcumin induce apoptosis through lysosomal membrane permeabilization-mediated autophagy. Oncogene. 2018;37(38):5205-5220.
Hoang B, Benavides A, Shi Y, et al. The PP242 mammalian target of rapamycin (mTOR) inhibitor activates extracellular signal-regulated kinase (ERK) in multiple myeloma cells via a target of rapamycin complex 1 (TORC1)/eukaryotic translation initiation factor 4E (eIF-4E)/RAF pathway and activation is a mechanism of resistance. J Biol Chem. 2012;287(26):21796-21805.
Zeng Z, Shi YX, Tsao T, et al. Targeting of mTORC1/2 by the mTOR kinase inhibitor PP242 induces apoptosis in AML cells under conditions mimicking the bone marrow microenvironment. Blood. 2012;120(13):2679-2689.
Jin HO, Hong SE, Park JA, et al. Inhibition of JNK-mediated autophagy enhances NSCLC cell sensitivity to mTORC1/2 inhibitors. Sci Rep. 2016;6(1):28945.
Lin X, Han L, Weng J, Wang K, Chen T. Rapamycin inhibits proliferation and induces autophagy in human neuroblastoma cells. Biosci Rep. 2018;38:6.
Cristofani R, Montagnani Marelli M, Cicardi ME, et al. Dual role of autophagy on docetaxel-sensitivity in prostate cancer cells. Cell Death Dis. 2018;9(9):889.
Zhao S, Lu N, Chai YYX. Rapamycin inhibits tumor growth of human osteosarcomas. J BUON. 2015;20(2):588-594.
Cheng PH, Lian S, Zhao R, Rao XM, McMasters KM, Zhou HS. Combination of autophagy inducer rapamycin and oncolytic adenovirus improves antitumor effect in cancer cells. Virol J. 2013;10:293.
Edinger AL, Linardic CM, Chiang GG, Thompson CB, Abraham RT. Differential effects of rapamycin on mammalian target of rapamycin signaling functions in mammalian cells. Cancer Res. 2003;63(23):8451-8460.
Li S, Yang G, Zhu X, Cheng L, Sun Y, Zhao Z. Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway. Oncol Rep. 2017;38(3):1637-1644.
Shi H, Zhang L, Zhang C, Hao Y, Zhao X. Rapamycin may inhibit murine S180 sarcoma growth by regulating the pathways associated with autophagy and cancer stem cells. J Cancer Res Ther. 2019;15(2):398-403.
Huang S, Houghton PJ. Inhibitors of mammalian target of rapamycin as novel antitumor agents: from bench to clinic. Curr Opinion Investig Drugs. 2002;3(2):295-304.
Fan QW, Cheng C, Hackett C, et al. Akt and autophagy cooperate to promote survival of drug-resistant glioma. Sci Signal. 2010;3(147):81.
Djuzenova CS, Fiedler V, Memmel S, et al. Differential effects of the Akt inhibitor MK-2206 on migration and radiation sensitivity of glioblastoma cells. BMC Cancer. 2019;19(1):299.
Button RW, Vincent JH, Strang CJ, Luo S. Dual PI-3 kinase/mTOR inhibition impairs autophagy flux and induces cell death independent of apoptosis and necroptosis. Oncotarget. 2016;7(5):5157.
Chen H, Potts K, Murray A, Hitt M, Moore R. Combined inhibition of autophagy with mTOR inhibitor to enhance cell death in renal cell carcinoma. J Clin Oncol. 2017;35(6_suppl):450-450.
Chang L, Graham PH, Hao J, et al. PI3K/Akt/mTOR pathway inhibitors enhance radiosensitivity in radioresistant prostate cancer cells through inducing apoptosis, reducing autophagy, suppressing NHEJ and HR repair pathways. Cell Death Dis. 2014;5(10):e1437.
D'Amato V, Rosa R, D'Amato C, et al. The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models. Br J Cancer. 2014;110(12):2887-2895.
Liu T, Sun Q, Li Q, et al. Dual PI3K/mTOR inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma. Mol Cancer Ther. 2015;14(2):429-439.
Chang Z, Shi G, Jin J, et al. Dual PI3K/mTOR inhibitor NVP-BEZ235-induced apoptosis of hepatocellular carcinoma cell lines is enhanced by inhibitors of autophagy. Int J Mol Med. 2013;31(6):1449-1456.
Ma Y, Jin Z, Yu K, Liu Q. NVP-BEZ235-induced autophagy as a potential therapeutic approach for multiple myeloma. Am J Transl Res. 2019;11(1):87-105.
Ji Y, Di W, Yang Q, Lu Z, Cai W, Wu J. Inhibition of autophagy increases proliferation inhibition and apoptosis induced by the PI3K/mTOR inhibitor NVP-BEZ235 in breast cancer cells. Clin Lab. 2015;61(8):1043-1051.
Li H, Jin X, Zhang Z, Xing Y, Kong X. Inhibition of autophagy enhances apoptosis induced by the PI3K/AKT/mTor inhibitor NVP-BEZ235 in renal cell carcinoma cells. Cell Biochem Funct. 2013;31(5):427-433.
Huang JC, Cui ZF, Chen SM, et al. NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma. Oncotarget. 2018;9(12):10483-10496.
Xin P, Li C, Zheng Y, et al. Efficacy of the dual PI3K and mTOR inhibitor NVP-BEZ235 in combination with imatinib mesylate against chronic myelogenous leukemia cell lines. Drug Des Dev Ther. 2017;11:1115-1126.
Nazim U, Moon JH, Lee JH, et al. Activation of autophagy flux by metformin downregulates cellular FLICE-like inhibitory protein and enhances TRAIL-induced apoptosis. Oncotarget. 2016;7(17):23468-23481.
Xiao Z, Gaertner S, Morresi-Hauf A, et al. Metformin triggers autophagy to attenuate drug-induced apoptosis in NSCLC cells, with minor effects on tumors of diabetic patients. Neoplasia. 2017;19(5):385-395.
Feng Y, Ke C, Tang Q, et al. Metformin promotes autophagy and apoptosis in esophageal squamous cell carcinoma by downregulating Stat3 signaling. Cell Death Dis. 2014;5(2):e1088-e1088.
Saladini S, Aventaggiato M, Barreca F, et al. Metformin impairs glutamine metabolism and autophagy in tumour cells. Cells. 2019;8(1):1-22.
Wang Y, Xu W, Yan Z, et al. Metformin induces autophagy and G0/G1 phase cell cycle arrest in myeloma by targeting the AMPK/mTORC1 and mTORC2 pathways. J Exp Clin Cancer Res. 2018;37(1):63.
Shi WY, Xiao D, Wang L, et al. Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy. Cell Death Dis. 2012;3(3):e275.
Lee KH, Hsu EC, Guh JH, et al. Targeting energy metabolic and oncogenic signaling pathways in triple-negative breast cancer by a novel adenosine monophosphate-activated protein kinase (AMPK) activator. J Biol Chem. 2011;286(45):39247-39258.
Plews RL, Mohd Yusof A, Wang C, et al. A novel dual AMPK activator/mTOR inhibitor inhibits thyroid cancer cell growth. J Clin Endocrinol Metab. 2015;100(5):E748-E756.
Dower CM, Bhat N, Gebru MT, et al. Targeted inhibition of ULK1 promotes apoptosis and suppresses tumor growth and metastasis in neuroblastoma. Mol Cancer Ther. 2018;17(11):2365-2376.
Lu J, Zhu L, Zheng L, et al. Overexpression of ULK1 represents a potential diagnostic marker for clear cell renal carcinoma and the antitumor effects of SBI-0206965. EBioMedicine. 2018;34:85-93.
Egan DF, Chun MGH, Vamos M, et al. Small molecule inhibition of the autophagy kinase ULK1 and identification of ULK1 substrates. Mol Cell. 2015;59(2):285-297.
Bhattacharya S, Piya S, McQueen T, Konopleva M, Andreeff M, Borthakur G. Inhibition of Unc-51 like autophagy activating kinase 1 (ULK1) is highly synergistic with chemotherapy and Bcl2 inhibition in acute myeloid leukemia (AML). Blood. 2017;130(suppl 1):S8-S9.
Bai LY, Chiu CF, Kapuriya NP, et al. BX795, a TBK1 inhibitor, exhibits antitumor activity in human oral squamous cell carcinoma through apoptosis induction and mitotic phase arrest. Eur J Pharmacol. 2015;769:287-296.
Ouyang L, Zhang L, Fu L, Liu B. A small-molecule activator induces ULK1-modulating autophagy-associated cell death in triple negative breast cancer. Autophagy. 2017;13(4):777-778.
Akin D, Wang SK, Habibzadegah-Tari P, et al. A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors. Autophagy. 2014;10(11):2021-2035.
Huang T, Kim CK, Alvarez AA, et al. MST4 phosphorylation of ATG4B regulates autophagic activity, tumorigenicity, and radioresistance in glioblastoma. Cancer Cell. 2017;32(6):840-855.e8.
Lin S, Yang L, Yao Y, et al. Flubendazole demonstrates valid antitumor effects by inhibiting STAT3 and activating autophagy. J Exp Clin Cancer Res. 2019;38(1):293.
Zhang L, Guo M, Li J, et al. Systems biology-based discovery of a potential Atg4B agonist (Flubendazole) that induces autophagy in breast cancer. Mol Biosyst. 2015;11(11):2860-2866.
Chauhan S, Ahmed Z, Bradfute SB, et al. Pharmaceutical screen identifies novel target processes for activation of autophagy with a broad translational potential. Nat Commun. 2015;6(1):8620.
Marinković M, Šprung M, Buljubašić M, Novak I. Autophagy modulation in cancer: current knowledge on action and therapy. Oxid Med Cell Longev. 2018;2018:1-18.
Sui X, Chen R, Wang Z, et al. Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment. Cell Death Dis. 2013;4(10):e838-e838.
Hall TM, Tétreault MP, Hamilton KE, Whelan KA. Autophagy as a cytoprotective mechanism in esophageal squamous cell carcinoma. Curr Opin Pharmacol. 2018;41:12-19.
Inui T, Chano T, Takikita-Suzuki M, Nishikawa M, Yamamoto G, Okabe H. Association of p62/SQSTM1 excess and oral carcinogenesis. PLOS One. 2013;8(9):e74398.
Cosway B, Lovat P. The role of autophagy in squamous cell carcinoma of the head and neck. Oral Oncol. 2016;54:1-6.
Chen Y, Wang G, Cai H, Sun Y, Ouyang L, Liu B. Deciphering the rules of in silico autophagy methods for expediting medicinal research. J Med Chem. 2019;62:6831-6842.
Ansari SS, Sharma AK, Soni H, et al. Induction of ER and mitochondrial stress by the alkylphosphocholine erufosine in oral squamous cell carcinoma cells. Cell Death Dis. 2018;9:296.
Wang YY, Zhou SF, Yang YX, et al. Bardoxolone methyl induces apoptosis and autophagy and inhibits epithelial-to-mesenchymal transition and stemness in esophageal squamous cancer cells. Drug Des Dev Ther. 2015:993-1026.
Qiu Y, Li C, Wang Q, Zeng X, Ji P. Tanshinone IIA induces cell death via Beclin-1-dependent autophagy in oral squamous cell carcinoma SCC-9 cell line. Cancer Med. 2018;7(2):397-407.
Lin N, Li Z, Wang D, Zheng K, Wu Y, Wang H. Mecambridine induces potent cytotoxic effects, autophagic cell death and modulation of the mTOR/PI3K/Akt signaling pathway in HSC-3 oral squamous cell carcinoma cells. Oncol Lett. 2018;15(1):292-296.
Liu D, Gao M, Yang Y, Qi Y, Wu K, Zhao S. Inhibition of autophagy promotes cell apoptosis induced by the proteasome inhibitor MG-132 in human esophageal squamous cell carcinoma EC9706 cells. Oncol Lett. 2015;9(5):2278-2282.
Wu N, Zhu Y, Xu X, et al. The anti-tumor effects of dual PI3K/mTOR inhibitor BEZ235 and histone deacetylase inhibitor Trichostatin A on inducing autophagy in esophageal squamous cell carcinoma. J Cancer. 2018;9(6):987-997.
Sophia J, Kowshik J, Dwivedi A, et al. Nimbolide, a neem limonoid inhibits cytoprotective autophagy to activate apoptosis via modulation of the PI3K/Akt/GSK-3β signalling pathway in oral cancer. Cell Death Dis. 2018;9(11):1087.
Cheng MF, Lin CS, Chen YH, et al. Inhibitory growth of oral squamous cell carcinoma cancer via bacterial prodigiosin. Mar Drugs. 2017;15(7):224.
Yu CC, Huang H, Hung SK, et al. AZD2014 radiosensitizes oral squamous cell carcinoma by inhibiting AKT/mTOR axis and inducing G1/G2/M cell cycle arrest. PLOS One. 2016;11(3):e0151942.
Huang KJ, Kuo CH, Chen SH, Lin CY, Lee YR. Honokiol inhibits in vitro and in vivo growth of oral squamous cell carcinoma through induction of apoptosis, cell cycle arrest and autophagy. J Cell Mol Med. 2018;22(3):1894-1908.
Weng JR, Bai LY, Ko HH, Tsai YT. Cyclocommunol induces apoptosis in human oral squamous cell carcinoma partially through a Mcl-1-dependent mechanism. Phytomedicine. 2018;39(July 2017):25-32.
Jiang L, Wang W, He Q, et al. Oleic acid induces apoptosis and autophagy in the treatment of tongue squamous cell carcinomas. Sci Rep. 2017;7(1):11277.
Yang Y, Sun X, Yang Y, et al. Gambogic acid enhances the radiosensitivity of human esophageal cancer cells by inducing reactive oxygen species via targeting Akt/mTOR pathway. Tumor Biol. 2016;37(2):1853-1862.
Bai LY, Weng JR, Hu JL, Wang D, Sargeant AM, Chiu CF. G15, a GPR30 antagonist, induces apoptosis and autophagy in human oral squamous carcinoma cells. Chem Biol Interact. 2013;206(2):375-384.
Bai LY, Chiu CF, Kapuriya NP, et al. BX795, a TBK1 inhibitor, exhibits antitumor activity in human oral squamous cell carcinoma through apoptosis induction and mitotic phase arrest. Eur J Pharmacol. 2015;769:287-296.
Bai LY, Chiu CF, Chiu SJ, Chu PC, Weng JR. FTY720 induces autophagy-associated apoptosis in human oral squamous carcinoma cells, in part, through a reactive oxygen species/Mcl-1-dependent mechanism. Sci Rep. 2017;7:5600.
Wu YH, Wu WS, Lin LC, et al. Bortezomib enhances radiosensitivity in oral cancer through inducing autophagy-mediated TRAF6 oncoprotein degradation. J Exp Clin Cancer Res. 2018;37(1):91.
Bai LY, Chiu CF, Chiu SJ, et al. Alphitolic acid, an anti-inflammatory triterpene, induces apoptosis and autophagy in oral squamous cell carcinoma cells, in part, through a p53-dependent pathway. J Funct Foods. 2015;18:368-378.
Lin CW, Chin HK, Lee SL, et al. Ursolic acid induces apoptosis and autophagy in oral cancer cells. Environ Toxicol. 2019;34(9):983-991.
Han HY, Kim H, Jeong SH, Lim DS, Ryu MH. Sulfasalazine induces autophagic cell death in oral cancer cells via Akt and ERK pathways. Asian Pac J Cancer Prev. 2014;15(16):6939-6944.
Hsieh MJ, Chien SY, Lin JT, Yang SF, Chen MK. Polyphyllin G induces apoptosis and autophagy cell death in human oral cancer cells. Phytomedicine. 2016;23(13):1545-1554.
Ko CP, Lin CW, Chen MK, Yang SF, Chiou HL, Hsieh MJ. Pterostilbene induce autophagy on human oral cancer cells through modulation of Akt and mitogen-activated protein kinase pathway. Oral Oncol. 2015;51(6):593-601.
Chiu CF, Bai LY, Kapuriya N, et al. Antitumor effects of BI-D1870 on human oral squamous cell carcinoma. Cancer Chemother Pharmacol. 2014;73(2):237-247.
Feng Y, Ke C, Tang Q, et al. Metformin promotes autophagy and apoptosis in esophageal squamous cell carcinoma by downregulating Stat3 signaling. Cell Death Dis. 2014;5(2):e1088-e1088.
Weng JR, Dokla EME, Bai LY, Chen CS, Chiu SJ, Shieh TM. A 5′ AMP-activated protein kinase enzyme activator, compound 59, induces autophagy and apoptosis in human oral squamous cell carcinoma. Basic Clin Pharmacol Toxicol. 2018;123(1):21-29.
Yu L, Wu WKK, Gu C, et al. Obatoclax impairs lysosomal function to block autophagy in cisplatin-sensitive and -resistant esophageal cancer cells. Oncotarget. 2016;7:12.
Shahin MI, Roy J, Hanafi M, et al. Synthesis and biological evaluation of novel 2-oxo-1,2-dihydroquinoline-4-carboxamide derivatives for the treatment of esophageal squamous cell carcinoma. Eur J Med Chem. 2018;155:516-530.
Jivan R, Damelin LH, Birkhead M, Rousseau AL, Veale RB, Mavri-Damelin D. Disulfiram/copper-disulfiram damages multiple protein degradation and turnover pathways and cytotoxicity is enhanced by metformin in oesophageal squamous cell carcinoma cell lines. J Cell Biochem. 2015;116(10):2334-2343.
Han B, Li W, Sun Y, Zhou L, Xu Y, Zhao X. A prolyl-hydroxylase inhibitor, ethyl-3,4-dihydroxybenzoate, induces cell autophagy and apoptosis in esophageal squamous cell carcinoma cellsvia up-regulation of BNIP3 and N-myc downstream-regulated gene-1. PLOS One. 2014;9(9):107204.
Li W, Hou G, Zhou D, et al. The roles of AKR1C1 and AKR1C2 in ethyl-3,4-dihydroxybenzoate induced esophageal squamous cell carcinoma cell death. Oncotarget. 2016;7(16):21542-21555.
Yang JG, Lu R, Ye XJ, Zhang J, Tan YQ, Zhou G. Icaritin reduces oral squamous cell carcinoma progression via the inhibition of STAT3 signaling. Int J Mol Sci. 2017;18(1):132.
Hsieh MJ, Lin CW, Chen MK, et al. Inhibition of cathepsin S confers sensitivity to methyl protodioscin in oral cancer cells via activation of p38 MAPK/JNK signaling pathways. Sci Rep. 2017;7:45039.
Li B, Lu M, X JX, Pan MX, Mao JW, Chen M. Inhibiting reactive oxygen species-dependent autophagy enhanced baicalein-induced apoptosis in oral squamous cell carcinoma. J Nat Med. 2017;71:433-441.
Liao C, Zheng K, Li Y, et al. Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca2+ release. Oncotarget. 2016;7(30):47387-47402.
Shi X, Wang L, Li X, et al. Dihydroartemisinin induces autophagy-dependent death in human tongue squamous cell carcinoma cells through DNA double-strand break-mediated oxidative stress. Oncotarget. 2017;8(28):45981-45993.
Coward J, Ambrosini G, Musi E, et al. Safingol (l-threo-sphinganine) induces autophagy in solid tumor cells through inhibition of PKC and the PI3-kinase pathway. Autophagy. 2009;5(2):184-193.
Masui A, Hamada M, Kameyama H, et al. Autophagy as a survival mechanism for squamous cell carcinoma cells in endonuclease g-mediated apoptosis. PLOS One. 2016;11(9):e0162786.
Utaipan T, Athipornchai A, Suksamrarn A, et al. Carbazole alkaloids from Murraya koenigii trigger apoptosis and autophagic flux inhibition in human oral squamous cell carcinoma cells. J Nat Med. 2017;71(1):158-169.
Sakagami H, Shimada C, Kanda Y, et al. Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells. Toxicol Rep. 2015;2:1281-1290.
Xie FJ, Zheng QQ, Qin J, Zhang LL, Han N, Mao WM. Autophagy inhibition stimulates apoptosis in oesophageal squamous cell carcinoma treated with fasudil. J Cancer. 2018;9(6):1050-1056.
Weng JR, Bai LY, Chiu SJ, et al. Divaricoside exerts antitumor effects, in part, by modulating Mcl-1 in human oral squamous cell carcinoma cells. Comput Struct Biotechnol J. 2019;17:151-159.
Park BS, Choi NE, Lee JH, et al. Crosstalk between fisetin-induced apoptosis and autophagy in human oral squamous cell carcinoma. J Cancer. 2019;10(1):138-146.
Tang Q, Li G, Wei X, et al. Resveratrol-induced apoptosis is enhanced by inhibition of autophagy in esophageal squamous cell carcinoma. Cancer Lett. 2013;336(2):325-337.
Vinas RP-T. New insights on the antitumoral properties of prodiginines. Curr Med Chem. 2010;17(21):2222-2231.
Pollak MN. Investigating metformin for cancer prevention and treatment: the end of the beginning. Cancer Discov. 2012;2(9):778-790.
Goard CA, Schimmer AD. An evidence-based review of obatoclax mesylate in the treatment of hematological malignancies. Core Evid. 2013;8:15-26.
Jivan R, Peres J, Damelin LH, et al. Disulfiram with or without metformin inhibits oesophageal squamous cell carcinoma in vivo. Cancer Lett. 2018;417:1-10.
Bano S, David MP, Indira AP. Salivary biomarkers for oral squamous cell carcinoma: an overview. IJSS Case Rep Rev. 2015;1(8):39-45.
Chen JY, Xu L, Fang WM, Han JY, Wang K, Zhu KS. Identification of PA28β as a potential novel biomarker in human esophageal squamous cell carcinoma. Tumor Biol. 2017;39(10):1-12.
Wang M, Smith JS, Wei WQ. Tissue protein biomarker candidates to predict progression of esophageal squamous cell carcinoma and precancerous lesions. Ann N Y Acad Sci. 2018;1434(1):59-69.
Jiang M, Li X, Quan X, et al. MiR-486 as an effective biomarker in cancer diagnosis and prognosis: a systematic review and meta-analysis. Oncotarget. 2018;9(17):13948-13958.
Saikumar J, Ramachandran K, Vaidya VS. Noninvasive micromarkers. Clin Chem. 2014;60(9):1158-1173.
Jamali L, Tofigh R, Tutunchi S, et al. Circulating microRNAs as diagnostic and therapeutic biomarkers in gastric and esophageal cancers. J Cell Physiol. 2018;233(11):8538-8550.
Mei LL, Qiu YT, Zhang B, Shi ZZ. MicroRNAs in esophageal squamous cell carcinoma: potential biomarkers and therapeutic targets. Cancer Biomark. 2017;19(1):1-9.
Sato Y, Motoyama S, Saito H, Minamiya Y. Novel candidate biomarkers of chemoradiosensitivity in esophageal squamous cell carcinoma: a systematic review. Eur Surg Res. 2016;56(3-4):141-153.
Pal A, Prasad TK, Jain A, et al. Testican 1 (SPOCK1) and protein tyrosine phosphatase, receptor type S (PTPRS) show significant increase in saliva of tobacco users with oral cancer. Transl Res Oral Oncol. 2018;3:1-11.
Venerito M, Helmke C, Jechorek D, et al. Leukotriene receptor expression in esophageal squamous cell cancer and non-transformed esophageal epithelium: a matched case control study. BMC Gastroenterol. 2016;16(1):85.
Li Y, Zhang Q, Peng B, Shao Q, Qian W, Zhang JY. Identification of glutathione S-transferase omega 1 (GSTO1) protein as a novel tumor-associated antigen and its autoantibody in human esophageal squamous cell carcinoma. Tumor Biol. 2014;35(11):10871-10877.
Khan MSR, Siddika F, Xu S, Liu XL, Shuang M, Liang HF. Diagnosing oral squamous cell carcinoma using salivary biomarkers. Bangabandhu Sheikh Mujib Med Univ J. 2018;11(1):1-10.
Panneer Selvam N, Sadaksharam J. Salivary interleukin-6 in the detection of oral cancer and precancer. Asia-Pac J Clin Oncol. 2015;11(3):236-241.
Ghallab NA, Shaker OG. Serum and salivary levels of chemerin and MMP-9 in oral squamous cell carcinoma and oral premalignant lesions. Clin Oral Investig. 2017;21(3):937-947.
Cui XB, Shen YY, Jin TT, et al. SLC39A6: A potential target for diagnosis and therapy of esophageal carcinoma. J Transl Med. 2015;13(1):1-16.
Chen X. Expression of cofilin-1 and transgelin in esophageal squamous cell carcinoma. Med Sci Monit. 2015;21:2659-2665.
Wang X, Peng Y, Xie M, et al. Identification of extracellular matrix protein 1 as a potential plasma biomarker of ESCC by proteomic analysis using iTRAQ and 2D-LC-MS/MS. Proteomics Clin Appl. 2017;11(9-10).
Gonzaga IM, Soares Lima SC, Nicolau MC, et al. TFF1 hypermethylation and decreased expression in esophageal squamous cell carcinoma and histologically normal tumor surrounding esophageal cells. Clin Epigen. 2017;9(1):130.
Vilen ST, Salo T, Sorsa T, Nyberg P. Fluctuating roles of matrix metalloproteinase-9 in oral squamous cell carcinoma. ScientificWorldJournal. 2013;2013:1-11.
Bahn JH, Zhang Q, Li F, et al. The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva. Clin Chem. 2015;61(1):221-230.
Elashoff D, Zhou H, Reiss J, et al. Prevalidation of salivary biomarkers for oral cancer detection. Cancer Epidemiol Biomark Prev. 2012;21(4):664-672.
Panta P, Wong DT. Salivary Biomarkers in Oral Cancer. Gewerbesraße 116330 - Cham SWITZERLAND: Springer International Publishing AG; 2019.
Wu DT, Tao O, Trinh N, et al. Saliva-a promising tool for diagnosing oral diseases. Curr Oral Health Rep. 2018;5(4):242-249.
Liu CJ, Lin SC, Yang CC, Cheng HW, Chang KW. Exploiting salivary miR-31 as a clinical biomarker of oral squamous cell carcinoma. Head Neck. 2012;34:219-224.
Momen-Heravi F, Trachtenberg AJ, Kuo WP, Cheng YS. Genomewide study of salivary microRNAs for detection of oral cancer. J Dent Res. 2014;93(July):86S-93S.
Zahran F, Ghalwash D, Shaker O, Al-Johani K, Scully C. Salivary microRNAs in oral cancer. Oral Dis. 2015;21(6):739-747.
Liu F, Tian T, Xia LL, Ding Y, Cormier RT, He Y. Induction therapy before surgery improves survival in patients with clinical T3N0 esophageal cancer: a nationwide study in Taiwan. Dis Esophagus. 2017;30(2):1-7.
Bai Y, Lin H, Fang Z, et al. Plasma microRNA-19a as a potential biomarker for esophageal squamous cell carcinoma diagnosis and prognosis. Biomark Med. 2017;11(5):431-441.
Wang C, Li Q, Liu F, et al. Serum miR-1297: a promising diagnostic biomarker in esophageal squamous cell carcinoma. Biomarkers. 2016;21(6):517-522.
Komatsu S, Ichikawa D, Hirajima S, et al. Plasma microRNA profiles: identification of miR-25 as a novel diagnostic and monitoring biomarker in oesophageal squamous cell carcinoma. Br J Cancer. 2014;111(8):1614-1624.
Shang M, Wang X, Zhang Y, Gao Z, Wang T, Liu R. LincRNA-ROR promotes metastasis and invasion of esophageal squamous cell carcinoma by regulating miR-145/FSCN1. OncoTargets Ther. 2018;11:639-649.
Sun J, Song K, Feng X, Gao S. MicroRNA-367 is a potential diagnostic biomarker for patients with esophageal squamous cell carcinoma. Biochem Biophys Res Commun. 2016;473(2):363-369.
Kaur J, Jacobs R, Huang Y, Salvo N, Politis C. Salivary biomarkers for oral cancer and pre-cancer screening: a review. Clin Oral Investig. 2018;22(2):633-640.
Yu JS, Chen YT, Chiang WF, et al. Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan. Proc Natl Acad Sci USA. 2016;113(41):11549-11554.
Zheng J, Sun L, Yuan W, et al. Clinical value of Naa10p and CEA levels in saliva and serum for diagnosis of oral squamous cell carcinoma. J Oral Pathol Med. 2018;47(9):830-835.
Heawchaiyaphum C, Pientong C, Phusingha P, et al. Peroxiredoxin-2 and zinc-alpha-2-glycoprotein as potentially combined novel salivary biomarkers for early detection of oral squamous cell carcinoma using proteomic approaches. J Proteomics. 2018;173(May 2017):52-61.
Shan J, Sun Z, Yang J, et al. Discovery and preclinical validation of proteomic biomarkers in saliva for early detection of oral squamous cell carcinomas. Oral Dis. 2018;25(1):97-107.
Shen Y, Ding Y, Ma Q, et al. Identification of novel circulating miRNA biomarkers for the diagnosis of esophageal squamous cell carcinoma and squamous dysplasia. Cancer Epidemiol Biomark Prev. 2019;28(7):1212-1220.
Xing S, Zheng X, Wei LQ, et al. Development and validation of a serum biomarker panel for the detection of esophageal squamous cell carcinoma through RNA transcriptome sequencing. J Cancer. 2017;8(12):2346-2355.
Jia K, Li W, Wang F, et al. Novel circulating peptide biomarkers for esophageal squamous cell carcinoma revealed by a magnetic bead-based MALDI-TOFMS assay. Oncotarget. 2016;7(17):23569-23580.
Tong YS, Wang XW, Zhou XL, et al. Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma. Mol Cancer. 2015;14(1):3.
Li X, Zhou F, Jiang C, et al. Identification of a DNA methylome profile of esophageal squamous cell carcinoma and potential plasma epigenetic biomarkers for early diagnosis. PLOS One. 2014;9(7):e103162.
Hu HB, Jie HY, Zheng XX. Three circulating LncRNA predict early progress of esophageal squamous cell carcinoma. Cell Physiol Biochem. 2016;40(1-2):117-125.
Zhao J, Fan YX, Yang Y, et al. Identification of potential plasma biomarkers for esophageal squamous cell carcinoma by a proteomic method. Int J Clin Exp Pathol. 2015;8(2):1535-1544.
Zhang J, Cao M, Chen J, et al. Serum anti-TOPO48 autoantibody as a biomarker for early diagnosis and prognosis in patients with esophageal squamous cell carcinoma. Clin Res Hepatol Gastroenterol. 2018;42(3):276-284.
Gao SG, Yang JQ, Ma ZK, et al. Preoperative serum immunoglobulin G and A antibodies to Porphyromonas gingivalis are potential serum biomarkers for the diagnosis and prognosis of esophageal squamous cell carcinoma. BMC Cancer. 2018;18(1):4-11.
Xu YW, Peng YH, Ran LQ, et al. Circulating levels of autoantibodies against L1-cell adhesion molecule as a potential diagnostic biomarker in esophageal squamous cell carcinoma. Clin Transl Oncol. 2017;19(7):898-906.
Xu YW, Liu CT, Huang XY, et al. Serum autoantibodies against STIP1 as a potential biomarker in the diagnosis of esophageal squamous cell carcinoma. Dis Markers. 2017;2017(2017):1-9.
Chen WX, Hong XB, Hong CQ, et al. Tumor-associated autoantibodies against Fascin as a novel diagnostic biomarker for esophageal squamous cell carcinoma. Clin Res Hepatol Gastroenterol. 2017;41(3):327-332.
Peng YH, Xu YW, Guo H, et al. Combined detection of serum Dickkopf-1 and its autoantibodies to diagnose esophageal squamous cell carcinoma. Cancer Med. 2016;5(7):1388-1396.
Gao H, Zheng Z, Mao Y, et al. Identification of tumor antigens that elicit a humoral immune response in the sera of Chinese esophageal squamous cell carcinoma patients by modified serological proteome analysis. Cancer Lett. 2014;344(1):54-61.
Cheng Y, Xu J, Guo J, et al. Circulating autoantibody to ABCC3 may be a potential biomarker for esophageal squamous cell carcinoma. Clin Transl Oncol. 2013;15(5):398-402.
Liu SGB, Lee CZK. Circulating autoantibody to CD25 may be a potential biomarker for early diagnosis of esophageal squamous cell carcinoma. Clin Transl Oncol. 2013;15:825-829.
Ye L, Guan S, Zhang C. Circulating autoantibody to FOXP3 may be a potential biomarker for esophageal squamous cell carcinoma. Tumor Biol. 2013;34:1873-1877.
Jin Y, Guan S, Liu L, Sun S, Lee KH, Wei J. Anti-p16 autoantibodies may be a useful biomarker for early diagnosis of esophageal cancer. Asia-Pac J Clin Oncol. 2015;11(4):e37-e41.
Liu Y, Xiong Z, Beasley A, D'Amico T, Chen X. Personalized and targeted therapy of esophageal squamous cell carcinoma: an update. Ann N Y Acad Sci. 2016;1381(1):66-73.
Malik UU, Zarina S, Pennington SR. Oral squamous cell carcinoma: Key clinical questions, biomarker discovery, and the role of proteomics. Arch Oral Biol. 2016;63:53-65.
Kang X, Chen K, Li Y, Li J, D'Amico TA, Chen X. Personalized targeted therapy for esophageal squamous cell carcinoma. World J Gastroenterol. 2015;21(25):7648-7658.
Wiedmann MW, Mössner J. New and emerging combination therapies for esophageal cancer. Cancer Manage Res. 2013;5(1):133-146.
Hadavand M, Hasni S. Exosomal biomarkers in oral diseases. Oral Dis. 2019;25(1):10-15.
Xu J, Camfield R, Gorski SM. The interplay between exosomes and autophagy-partners in crime. J Cell Sci. 2018;131(15).
Sento S, Sasabe E, Yamamoto T. Application of a persistent heparin treatment inhibits the malignant potential of oral squamous carcinoma cells induced by tumor cell-derived exosomes. PLOS One. 2016;11(2):e0148454.
Momen-Heravi F, Bala S. Emerging role of non-coding RNA in oral cancer. Cell Signal. 2018;42:134-143.
Zorrilla S, Pérez-Sayans M, Fais S, Logozzi M, Torreira M, García A. A pilot clinical study on the prognostic relevance of plasmatic exosomes levels in oral squamous cell carcinoma patients. Cancers (Basel). 2019;11(3):429-440.
Cai J, Gao N, Qiao B, Lin N, He W, Surgery M. Oral squamous cell carcinoma-derived exosomes promote M2 subtype macrophage polarization mediated by exosome-enclosed miR-29a-3p. Am J Physiol Cell Physiol. 2019;316:731.
Matsumoto Y, Kano M, Akutsu Y, et al. Quantification of plasma exosome is a potential prognostic marker for esophageal squamous cell carcinoma. Oncol Rep. 2016;36(5):2535-2543.
Li B, Song TN, Wang FR, et al. Tumor-derived exosomal HMGB1 promotes esophageal squamous cell carcinoma progression through inducing PD1+TAM expansion. Oncogenesis. 2019;8(17):17.
Luo A, Zhou X, Shi X, et al. Exosome-derived miR-339-5p mediates radiosensitivity by targeting Cdc25A in locally advanced esophageal squamous cell carcinoma. Oncogene. 2019;38:4990-5006.
Li L, Li C, Wang S, et al. Exosomes derived from hypoxic oral squamous cell carcinoma cells deliver miR-21 to normoxic cells to elicit a prometastatic phenotype. Cancer Res. 2016;76(7):1770-1780.
Liu T, Chen G, Sun D, et al. Exosomes containing miR-21 transfer the characteristic of cisplatin resistance by targeting PTEN and PDCD4 in oral squamous cell carcinoma. Acta Biochim Biophys Sin (Shanghai). 2017;49(9):808-816.
Li L, Cao B, Liang X, et al. Microenvironmental oxygen pressure orchestrates an anti- and pro-tumoral γδ T cell equilibrium via tumor-derived exosomes. Oncogene. 2019;38(15):2830-2843.
Tanaka Y, Kamohara H, Kinoshita K, Kurashige J. Clinical impact of serum exosomal microRNA-21 as a clinical biomarker in human esophageal squamous cell carcinoma. Cancer. 2013;119:1159-1167.
Baixauli F, López-Otín C, Mittelbrunn M. Exosomes and autophagy: coordinated mechanisms for the maintenance of cellular fitness. Front Immunol. 2014;5(Aug):1-6.
Murrow L, Malhotra R, Debnath J. ATG12-ATG3 interacts with Alix to promote basal autophagic flux and late endosome function. Nat Cell Biol. 2015;17(3):300-310.
Guo H, Chitiprolu M, Roncevic L, et al. Atg5 disassociates the V1V0-ATPase to promote exosome production and tumor metastasis independent of canonical macroautophagy. Dev Cell. 2017;43(6):716-730.