Abstract
Perspectives in the Treatment of RAS or BRAF Mutated Metastatic Colorectal Cancer Patients.
Highlights
Until a few years ago, the overall survival (OS) for metastatic colorectal cancer patients did not generally exceed 18–20 months in spite of a progressively evolving therapeutic armamentarium [1]
Alongside an environmental genesis in which diet could be a cause, it is known that mutations in certain genes [neuroblastoma rat sarcoma virus (RAS) (NRAS), Kirsten RAS (KRAS), mutant B rapidly accelerated fibrosarcoma (BRAF)], part of the downstream signaling pathways of the epidermal growth factor receptor (EGFR), are crucial in the process of carcinogenesis [3]
KRAS mutant NSCLC, colon, pancreatic cell line xenografts and patient-derived xenografts Four colon cancer cell lines Effects of treatments were tested on PDX SW480 and HT-29 CRC cells
Summary
Until a few years ago, the overall survival (OS) for metastatic colorectal cancer (mCRC) patients did not generally exceed 18–20 months in spite of a progressively evolving therapeutic armamentarium [1]. Two farnesyltransferase inhibitors (FTI), tipifarnib and lonafarnib, were tested in phase III clinical trials in patients with advanced stage pancreatic cancer, NSCLC, mCRC, and acute myeloid leukemia They showed no clinical efficacy in KRAS-driven cancer, leading to the conclusion that targeting post-translational modifications in RAS are ineffective [18]. While the most common adverse events related to the treatment were diarrhea (67%), rash (48%), and fatigue (40%), clinical activity of atezolizumab and cobimetinib was reported regardless of KRAS/BRAF state This potential synergistic activity was not confirmed in a subsequent phase III study, even though the recruitment of patients with MSI-H was no more than 5% emphasizing that the benefits of immunotherapy should be limited only to them [22]. BRAF, a serine-threonine protein kinase, is the primary effector of RAS signaling and is mutated in roughly 10% of mCRC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
