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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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New therapeutic strategies for BRAF mutant colorectal cancers

Ryan B Corcoran1

  • 11 Massachusetts General Hospital Cancer Center, Boston, MA 02129, USA ; 2 Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

Journal of Gastrointestinal Oncology
|December 24, 2015
PubMed

Insights

BRAF mutations in colorectal cancer (CRC) predict poor outcomes. While BRAF inhibitors work for melanoma, they are ineffective alone in CRC due to resistance mechanisms. Novel strategies are emerging in clinical trials.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Oncogenic BRAF mutations occur in approximately 10% of colorectal cancers (CRCs).
  • BRAF mutations are associated with a poor prognosis in CRC patients.
  • BRAF inhibitors are effective in BRAF-mutant melanoma but not in BRAF-mutant CRC monotherapy.

Purpose of the Study:

  • To review the molecular mechanisms of BRAF inhibitor resistance in BRAF-mutant CRC.
  • To discuss novel therapeutic strategies for BRAF-mutant CRC currently in clinical trials.

Main Methods:

  • Literature review of studies on BRAF inhibitor resistance in CRC.
  • Analysis of molecular mechanisms underlying resistance.
  • Overview of therapeutic approaches in clinical trials.

Main Results:

  • BRAF inhibitor monotherapy is ineffective in BRAF-mutant CRC.
  • Specific molecular mechanisms contribute to BRAF inhibitor resistance in CRC.
  • Emerging therapeutic strategies show promising clinical activity.

Conclusions:

  • Understanding BRAF inhibitor resistance mechanisms is crucial for developing effective treatments for BRAF-mutant CRC.
  • Novel therapeutic strategies are under investigation and show promise in clinical trials for this patient population.
Keywords:
BRAFBRAF inhibitorclinical trialscolorectal cancer (CRC)

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