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BRAF in metastatic colorectal cancer: the future starts now

Armando Orlandi^1,2,3, Alessandra Calegari¹, Alessandro Inno⁴

¹Medical Oncology Department, Università Cattolica del Sacro Cuore, Rome, Italy.

Pharmacogenomics

|December 1, 2015

Abstract:

BRAF mutations are detectable in about 5-15% of metastatic colorectal cancer (mCRC) patients and represent a clear negative prognostic factor. While in BRAF-mutated (BRAFmt) metastatic melanoma TKI target therapies (BRAF and MEK inhibitor), both alone or in combination, have shown significant efficacy, in BRAFmt CRC single-agent BRAF-inhibitors as well as chemotherapy seem to be ineffective. The critical role of EGFR in CRC and its multiple downstreaming pathways seem to be involved in this lack of response. In recent years, preclinical investigations and retrospective studies slowly increased our knowledge on BRAFmt CRC. This review analyses preclinical data and discusses several clinical trials in order to explore new therapeutic strategies targeting BRAFmt mCRC.

Insights

BRAF mutations in metastatic colorectal cancer (mCRC) patients are linked to poor prognosis. This review explores new therapeutic strategies for BRAF-mutated mCRC, addressing treatment resistance to targeted therapies.

Area of Science:

Oncology
Molecular Biology
Genetics

Background:

BRAF mutations occur in 5-15% of metastatic colorectal cancer (mCRC) cases.
These mutations signify a poor prognostic factor in mCRC.
BRAF-mutated (BRAFmt) metastatic melanoma responds well to targeted therapies, unlike BRAFmt CRC.

Purpose of the Study:

To review preclinical data on BRAF-mutated colorectal cancer.
To discuss clinical trials for BRAFmt mCRC.
To explore novel therapeutic strategies for BRAFmt mCRC.

Main Methods:

Analysis of preclinical investigations.
Review of retrospective studies.
Discussion of clinical trial data.

Main Results:

BRAF inhibitors and chemotherapy show limited efficacy in BRAFmt CRC.
EGFR signaling pathways may contribute to treatment resistance.
Growing knowledge from preclinical and retrospective studies.

Conclusions:

BRAFmt mCRC presents unique therapeutic challenges.
Investigating combination therapies and targeting EGFR pathways is crucial.
Further research is needed to develop effective treatments for BRAFmt mCRC.

Read full analysis

Keywords:

BRAF colorectal cancer immunotherapy target therapy

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