Significance of tumor microenvironment in acquiring resistance to vascular endothelial growth factor-tyrosine kinase inhibitor and recent advance of systemic treatment of clear cell renal cell carcinoma.
Angiogenesis Inducing Agents
Carcinoma, Renal Cell
/ drug therapy
Drug Resistance, Neoplasm
Humans
Immune Checkpoint Inhibitors
/ therapeutic use
Immunotherapy
Kidney Neoplasms
/ drug therapy
Molecular Targeted Therapy
Protein Kinase Inhibitors
/ therapeutic use
Protein-Tyrosine Kinases
/ antagonists & inhibitors
TOR Serine-Threonine Kinases
/ antagonists & inhibitors
Tumor Microenvironment
Vascular Endothelial Growth Factor A
/ antagonists & inhibitors
VEGF-TKI
angiogenesis
immunotherapy
molecular target therapy
renal cell carcinoma
resistance
tumor microenvironment
Journal
Pathology international
ISSN: 1440-1827
Titre abrégé: Pathol Int
Pays: Australia
ID NLM: 9431380
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
06
05
2020
revised:
20
06
2020
accepted:
24
06
2020
pubmed:
12
7
2020
medline:
17
8
2021
entrez:
12
7
2020
Statut:
ppublish
Résumé
The development of systemic therapies, including vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKI) and mammalian target of rapamycin (mTOR) inhibitors, represents a major breakthrough in the treatment of patients with renal cell carcinoma (RCC). However, inherent resistance is observed in some patients and acquired resistance commonly develops in many patients within several months of the initiation of systemic therapies. Since these treatments rarely cure patients, their aim is to suppress tumor progression and prolong survival. Therefore, the establishment of dependable criteria that predict responses and resistance to systemic therapies is clinically important, and the underlying molecular mechanisms also need to be elucidated for the future development of more effective therapies. We herein review recent advances in research on the molecular mechanisms underlying resistance, with a focus on morphological characteristics, tumor angiogenesis, and the tumor immune microenvironment in RCC and their relationships with VEGF-TKI treatments. Recent therapies using immune checkpoint inhibitors (ICI) and newly developed VEGF-TKI also appear to be effective for advanced RCC, with stable and durable responses to ICI being observed in some RCC patients. These new drugs and their outcomes have been briefly described.
Substances chimiques
Angiogenesis Inducing Agents
0
Immune Checkpoint Inhibitors
0
Protein Kinase Inhibitors
0
VEGFA protein, human
0
Vascular Endothelial Growth Factor A
0
MTOR protein, human
EC 2.7.1.1
Protein-Tyrosine Kinases
EC 2.7.10.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
712-723Subventions
Organisme : The Ministry of Education, Culture, Sports, Science, and Technology of Japan
ID : 19K07468
Organisme : The Ministry of Education, Culture, Sports, Science, and Technology of Japan
ID : 17K11159
Organisme : The Ministry of Education, Culture, Sports, Science, and Technology of Japan
ID : 19H03792
Organisme : The Ministry of Education, Culture, Sports, Science, and Technology of Japan
ID : 18H02939
Organisme : Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT)
ID : 19K07468
Organisme : Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT)
ID : 17K11159
Organisme : Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT)
ID : 19H03792
Organisme : Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT)
ID : 18H02939
Informations de copyright
© 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
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