Mutational profiles associated with resistance in patients with BRAFV600E mutant colorectal cancer treated with cetuximab and encorafenib +/- binimetinib or alpelisib.

British Journal of Cancer
S HuijbertsFrans L Opdam

Abstract

Treatment strategies inhibiting BRAF in combination with EGFR have been developed in patients with BRAFV600E mutant metastatic colorectal cancer, but intrinsic and secondary resistance remains a challenge. We aimed to investigate which genetic alterations cause intrinsic non-response and/or acquired resistance in these patients receiving therapies consisting of a backbone of BRAF and EGFR inhibition. This was a cohort study on genetic alterations in patients with BRAFV600E mutant advanced colorectal cancer treated with inhibitors of the MAPK pathway. We examined tumour tissue for genetic alterations at baseline, during treatment and at progression. In total, 37 patients were included in this cohort. Genetic alterations in EGFR and in PIK3CA are associated with non-response. A greater fraction of non-responders (75%) versus responders (46%) had at least one genetic alteration in other genes than TP53, APC or BRAF. Secondary resistance mutations (n = 16 patients) were observed most frequently in the PI3K pathway (n = 6) and in receptor tyrosine kinases (n = 4), leading to increased upstream signalling. Genetic alterations in the PI3K and upstream receptor tyrosine kinases were mostly associated with intrinsic and acquired resista...Continue Reading

References

Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Samy LamouilleRik Derynck
Jan 16, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rona YaegerLeonard B Saltz
Sep 24, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ryan B CorcoranScott Kopetz
Oct 16, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Scott KopetzLeonard Saltz
Jun 30, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David BarrasMauro Delorenzi
Jul 7, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E Van CutsemD Arnold
Mar 12, 2017·International Journal of Molecular Sciences·Nourah Mohammad ObaidWeei-Yuarn Huang
Apr 14, 2017·Journal of Cellular Physiology·Afsane BahramiAmir Avan
Feb 13, 2018·Cancer Discovery·Ryan B CorcoranEric Van Cutsem
Mar 21, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric Van CutsemJosep Tabernero
Oct 1, 2019·The New England Journal of Medicine·Scott KopetzJosep Tabernero
Oct 31, 2019·International Journal of Molecular Sciences·Francesco CaputoFabio Gelsomino
Feb 13, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gary MiddletonRyan B Corcoran

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsies
the
biopsy

Related Concepts

Related Feeds

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.