New advances in the clinical management of RAS and BRAF mutant colorectal cancer patients

ABSTRACT

Introduction

In colorectal carcinogenesis, genetic alterations in RAS and BRAF oncogenes play an important role for cancer initiation and/or progression and represent a key focus in the search for targeted therapies. Despite many years of research and a great amount of studies, until very recently this pathway was considered extremely hard to downregulate to obtain a significant clinical impact in colorectal cancer patients. But better times are coming with the advent of new promising drugs and combinations strategies.

Areas covered

In this review, we go over the biological characteristics of the MAPK pathway in colorectal tumors, while illustrating the clinical correlation of RAS and BRAF mutations, particularly its prognostic and predictive value. We also present newly data about recent improvements in the treatment strategy for patients harboring these types of tumors.

Expert commentary

With great advances in the knowledge of molecular basis of RAS and BRAF mutant colorectal cancer in conjunction with biotechnology development and the constant effort for improvement, in the near future many new therapeutic options would be available for the management of this group of patient with dismal prognosis.

KEYWORDS:

• Colorectal cancer
• mapk
• ras
• braf
• targeted therapy
• egfr
• mek

Article highlights

• Colorectal cancer is one of the most prevalent forms of cancer, leading to a high number of cancer-related death yearly around the world.

• Alterations in MAPK pathway represent a frequent underlying molecular mechanism of colorectal tumorigenesis.

• RAS and BRAF genes mutations are of particular interest, due to its prognostic and predictive value.

• In advanced colorectal patients, upfront molecular testing is mandatory since mutation detection has implications in the therapeutic strategy and its impact on long-term survival.

• Recently, new targeted drugs directed against KRAS and BRAF have shown promising results in clinical trials, as monotherapy or in combination regimens.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR723; the Instituto de Salud Carlos III, co-funded by FEDER funds –a way to build Europe– grant PI17–00092 and the Spanish Association Against Cancer (AECC) Scientific Foundation.