The Role of BRAF in Metastatic Colorectal Carcinoma-Past, Present, and Future.

Abstract:

:With a global incidence of 1.8 million cases, colorectal cancer represents one of the most common cancers worldwide. Despite impressive improvements in treatment efficacy through cytotoxic and biological agents, the cancer-related death burden of metastatic colorectal cancer (mCRC) is still high. mCRC is not a genetically homogenous disease and various mutations influence disease development. Up to 12% of mCRC patients harbor mutations of the signal transduction molecule BRAF, the most prominent being BRAFV600E. In mCRC, BRAFV600E mutation is a well-known negative prognostic factor, and is associated with a dismal prognosis. The currently approved treatments for BRAF-mutated mCRC patients are of little impact, and there is no treatment option superior to others. However, the gradual molecular understanding over the last decades of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway, resulted in the development of new therapeutic strategies targeting the involved molecules. Recently published and ongoing studies administering a combination of different inhibitors (e.g., BRAF, MEK, and EGFR) showed promising results and represent the new standard of care. In this review, we present, both, the molecular and clinical aspects of BRAF-mutated mCRC patients, and provide an update on the current and future treatment approaches that might direct the therapy of mCRC in a new era.

journal_name

Int J Mol Sci

authors

Djanani A,Eller S,Öfner D,Troppmair J,Maglione M

doi

10.3390/ijms21239001

subject

Has Abstract

pub_date

2020-11-26 00:00:00

issue

23

issn

1422-0067

pii

ijms21239001

journal_volume

21

pub_type

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