BRAF-mutated colorectal cancer: Clinical and molecular insights

Francesco Caputo, Chiara Santini, Camilla Bardasi, Krisida Cerma, Andrea Casadei-Gardini, Andrea Spallanzani, Kalliopi Andrikou, Stefano Cascinu, Fabio Gelsomino

Research output: Contribution to journalReview articlepeer-review

Abstract

Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. It is a heterogeneous disease, which can be classified into different subtypes, characterized by specific molecular and morphological alterations. In this context, BRAF mutations are found in about 10% of CRC patients and define a particular subtype, characterized by a dismal prognosis, with a median survival of less than 12 months. Chemotherapy plus bevacizumab is the current standard therapy in first-line treatment of BRAF-mutated metastatic CRC (mCRC), with triplet (FOLFOXIRI) plus bevacizumab as a valid option in patients with a good performance status. BRAF inhibitors are not so effective as compared to melanoma, because of various resistance mechanisms. However, the recently published results of the BEACON trial will establish a new standard of care in this setting. This review provides insights into the molecular underpinnings underlying the resistance to standard treatment of BRAF-mutated CRCs, with a focus on their molecular heterogeneity and on the research perspectives both from a translational and a clinical point of view.

Original languageEnglish
Article number5369
JournalInternational Journal of Molecular Sciences
Volume20
Issue number21
DOIs
Publication statusPublished - Nov 1 2019

Keywords

  • BRAF inhibitors
  • BRAF mutation
  • Colorectal cancer
  • Molecular targets
  • Targeted therapy

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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