Routine Molecular Pathology Diagnostics in Precision Oncology.
Journal
Deutsches Arzteblatt international
ISSN: 1866-0452
Titre abrégé: Dtsch Arztebl Int
Pays: Germany
ID NLM: 101475967
Informations de publication
Date de publication:
16 Apr 2021
16 Apr 2021
Historique:
entrez:
4
2
2021
pubmed:
5
2
2021
medline:
5
2
2021
Statut:
aheadofprint
Résumé
Technical advances in the field of molecular genetics permit precise genomic characterization of malignant tumors. This has not only improved our understanding of tumor biology but also paved the way for molecularly stratified treatment strategies in routine clinical practice. A selective search of PubMed to identify literature on molecular pathology methods, their indications, the challenges associated with molecular findings, and future developments. Tumors can be characterized with the aid of immunohistochemistry, in-situ hybridization, and sequencing of DNA or RNA. The benefits of molecularly stratified tumor treatment have been demonstrated by randomized clinical trials on numerous tumor entities, e.g., non-small-cell lung cancer, colorectal cancer, and breast cancer. Therefore, initiation of specific treatment for these entities should be preceded by molecular pathology biomarker analyses, generally carried out on tumor tissue. Randomized controlled trials and non-controlled studies show that enhanced progression-free survival ensues if the pharmacological treatment is oriented on the findings of molecular pathology diagnostics. In next-generation sequencing, numerous relevant gene sequences or even whole genes can be sequenced in parallel, dispensing with complex staged diagnostics and reducing the use of biomaterials. These new methods also complement the currently relevant predictive biomarkers by permitting the investigation of genetic alterations presently of interest in the context of clinical studies. Prior to widespread routine clinical application, however, sequencing of large gene panels or whole genomes or exomes need to be even more stringently validated. Quality-assured molecular pathology assays are universally available for the determination of currently relevant predictive biomarkers. However, the integration of extensive genomic analyses into routine molecular pathology diagnostics represents a future challenge in precision oncology.
Sections du résumé
BACKGROUND
BACKGROUND
Technical advances in the field of molecular genetics permit precise genomic characterization of malignant tumors. This has not only improved our understanding of tumor biology but also paved the way for molecularly stratified treatment strategies in routine clinical practice.
METHODS
METHODS
A selective search of PubMed to identify literature on molecular pathology methods, their indications, the challenges associated with molecular findings, and future developments.
RESULTS
RESULTS
Tumors can be characterized with the aid of immunohistochemistry, in-situ hybridization, and sequencing of DNA or RNA. The benefits of molecularly stratified tumor treatment have been demonstrated by randomized clinical trials on numerous tumor entities, e.g., non-small-cell lung cancer, colorectal cancer, and breast cancer. Therefore, initiation of specific treatment for these entities should be preceded by molecular pathology biomarker analyses, generally carried out on tumor tissue. Randomized controlled trials and non-controlled studies show that enhanced progression-free survival ensues if the pharmacological treatment is oriented on the findings of molecular pathology diagnostics. In next-generation sequencing, numerous relevant gene sequences or even whole genes can be sequenced in parallel, dispensing with complex staged diagnostics and reducing the use of biomaterials. These new methods also complement the currently relevant predictive biomarkers by permitting the investigation of genetic alterations presently of interest in the context of clinical studies. Prior to widespread routine clinical application, however, sequencing of large gene panels or whole genomes or exomes need to be even more stringently validated.
CONCLUSION
CONCLUSIONS
Quality-assured molecular pathology assays are universally available for the determination of currently relevant predictive biomarkers. However, the integration of extensive genomic analyses into routine molecular pathology diagnostics represents a future challenge in precision oncology.
Identifiants
pubmed: 33536117
pii: arztebl.m2021.0025
doi: 10.3238/arztebl.m2021.0025
pmc: PMC8287073
doi:
pii:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
Genome Biol. 2011 Aug 25;12(8):125
pubmed: 21867570
Nat Med. 2019 May;25(5):744-750
pubmed: 31011206
Am J Surg Pathol. 2018 Feb;42(2):e11-e27
pubmed: 29076877
Histopathology. 2021 Feb;78(3):401-413
pubmed: 32791559
N Engl J Med. 2012 Nov 8;367(19):1783-91
pubmed: 23020162
Transl Lung Cancer Res. 2020 Jun;9(3):603-616
pubmed: 32676323
Lancet. 2010 Aug 28;376(9742):687-97
pubmed: 20728210
J Clin Oncol. 2019 Jun 10;37(17):1460-1469
pubmed: 30892987
Trends Pharmacol Sci. 2019 Mar;40(3):172-186
pubmed: 30736982
N Engl J Med. 2019 May 16;380(20):1929-1940
pubmed: 31091374
Lancet Oncol. 2015 Oct;16(13):1324-34
pubmed: 26342236
Nat Med. 2015 Nov;21(11):1350-6
pubmed: 26457759
J Mol Diagn. 2017 Jan;19(1):137-146
pubmed: 27840062
N Engl J Med. 2014 Nov 20;371(21):1963-71
pubmed: 25264305
J Clin Oncol. 2020 Jan 20;38(3):214-222
pubmed: 31765263
J Cell Physiol. 2018 Jan;233(1):378-386
pubmed: 28266716
J Mol Diagn. 2017 Sep;19(5):722-732
pubmed: 28723342
Lancet Oncol. 2016 Jun;17(6):738-746
pubmed: 27108243
Ther Adv Med Oncol. 2017 Jun;9(6):387-404
pubmed: 28607578
N Engl J Med. 2020 Sep 3;383(10):944-957
pubmed: 32877583
Lancet Oncol. 2020 Jan;21(1):44-59
pubmed: 31786121
N Engl J Med. 2018 Jan 11;378(2):113-125
pubmed: 29151359
J Hematol Oncol. 2019 May 31;12(1):54
pubmed: 31151482
Ann Oncol. 2016 Sep;27 Suppl 3:iii25-iii34
pubmed: 27573753
Am J Surg Pathol. 2017 Nov;41(11):1547-1551
pubmed: 28719467
Nat Med. 2019 May;25(5):751-758
pubmed: 31011205
N Engl J Med. 2014 Dec 4;371(23):2167-77
pubmed: 25470694
Clin Cancer Res. 2017 Jul 26;:
pubmed: 28747339
J Clin Oncol. 2019 Mar 1;37(7):537-546
pubmed: 30620668
N Engl J Med. 2015 Jan 1;372(1):30-9
pubmed: 25399551
N Engl J Med. 2018 Feb 22;378(8):731-739
pubmed: 29466156
Nature. 2020 Feb;578(7793):94-101
pubmed: 32025018
N Engl J Med. 2015 Oct 22;373(17):1627-39
pubmed: 26412456
N Engl J Med. 2019 Jul 25;381(4):317-327
pubmed: 31157963
Cancer Sci. 2018 Mar;109(3):513-522
pubmed: 29345757
Virchows Arch. 2018 Apr;472(4):557-565
pubmed: 29374318
J Clin Oncol. 2019 Jun 1;37(16):1370-1379
pubmed: 30892989
J Clin Oncol. 2018 Apr 20;36(12):1199-1206
pubmed: 29373100
N Engl J Med. 2019 Nov 21;381(21):2020-2031
pubmed: 31562796
Mod Pathol. 2020 Jan;33(1):4-17
pubmed: 31383961
N Engl J Med. 2018 Dec 27;379(26):2495-2505
pubmed: 30345884
Ann Oncol. 2019 Sep 1;30(9):1417-1427
pubmed: 31268127
Mod Pathol. 2016 Oct;29(10):1165-72
pubmed: 27389313
N Engl J Med. 2017 Aug 10;377(6):523-533
pubmed: 28578601
N Engl J Med. 2017 Mar 16;376(11):1015-1026
pubmed: 28212060
Cancer Discov. 2016 Oct;6(10):1118-1133
pubmed: 27432227
Virchows Arch. 2010 Sep;457(3):299-307
pubmed: 20665045
J Clin Oncol. 2010 Nov 1;28(31):4697-705
pubmed: 20921465
Lancet Oncol. 2017 Oct;18(10):1307-1316
pubmed: 28919011
Comput Struct Biotechnol J. 2019 Sep 11;17:1339-1347
pubmed: 31762957
Nat Med. 2017 Sep 8;23(9):1028-1035
pubmed: 28886003
Genes Chromosomes Cancer. 2020 Aug;59(8):445-453
pubmed: 32319699
Front Oncol. 2020 May 08;10:533
pubmed: 32457826
J Med Genet. 2020 Aug;57(8):509-518
pubmed: 32152249
Genome Med. 2018 Mar 15;10(1):18
pubmed: 29544535