RAS and BRAF in metastatic colorectal cancer management

Jun Gong, May Cho, Marwan Fakih

Research output: Contribution to journalReview article

24 Citations (Scopus)

Abstract

The treatment of metastatic colorectal cancer (mCRC) has been further refined with the development of monoclonal antibodies, cetuximab and panitumumab, towards the epidermal growth factor receptor (EGFR). Anti-EGFR therapy has afforded improved survival in those with wild-type RAS mCRC but provides no benefit and even harm in those with RAS-mutant tumors. BRAF mutations have also been shown to predict lack of clinically meaningful benefit to anti-EGFR therapy in mCRC. Mechanisms of resistance to EGFR blockade in wild-type RAS or BRAF metastatic colorectal tumors appear to converge on the mitogen-activated protein kinase (MAPK) signaling pathway. Clinical trials involving combined BRAF, EGFR, and/or MAPK kinase (MEK) inhibition have shown promising activity in BRAF-mutant mCRC. Here, we review pivotal clinical trials that have redefined our treatment approach in mCRC with respect to anti-EGFR therapy based on RAS and BRAF mutation status. Future studies will likely focus on improving efficacy of anti-EGFR-based therapy in mCRC through sustained MAPK pathway inhibition.

Original languageEnglish (US)
Pages (from-to)687-704
Number of pages18
JournalJournal of Gastrointestinal Oncology
Volume7
Issue number5
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Epidermal Growth Factor Receptor
Colorectal Neoplasms
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinases
Clinical Trials
Mutation
Therapeutics
Monoclonal Antibodies
Neoplasms

Keywords

  • BRAF
  • Cetuximab
  • Colorectal cancer (CRC)
  • Panitumumab
  • RAS

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

Cite this

RAS and BRAF in metastatic colorectal cancer management. / Gong, Jun; Cho, May; Fakih, Marwan.

In: Journal of Gastrointestinal Oncology, Vol. 7, No. 5, 01.01.2016, p. 687-704.

Research output: Contribution to journalReview article

Gong, Jun ; Cho, May ; Fakih, Marwan. / RAS and BRAF in metastatic colorectal cancer management. In: Journal of Gastrointestinal Oncology. 2016 ; Vol. 7, No. 5. pp. 687-704.
@article{e504b72a57e84b63a1b8a50ef1f097bf,
title = "RAS and BRAF in metastatic colorectal cancer management",
abstract = "The treatment of metastatic colorectal cancer (mCRC) has been further refined with the development of monoclonal antibodies, cetuximab and panitumumab, towards the epidermal growth factor receptor (EGFR). Anti-EGFR therapy has afforded improved survival in those with wild-type RAS mCRC but provides no benefit and even harm in those with RAS-mutant tumors. BRAF mutations have also been shown to predict lack of clinically meaningful benefit to anti-EGFR therapy in mCRC. Mechanisms of resistance to EGFR blockade in wild-type RAS or BRAF metastatic colorectal tumors appear to converge on the mitogen-activated protein kinase (MAPK) signaling pathway. Clinical trials involving combined BRAF, EGFR, and/or MAPK kinase (MEK) inhibition have shown promising activity in BRAF-mutant mCRC. Here, we review pivotal clinical trials that have redefined our treatment approach in mCRC with respect to anti-EGFR therapy based on RAS and BRAF mutation status. Future studies will likely focus on improving efficacy of anti-EGFR-based therapy in mCRC through sustained MAPK pathway inhibition.",
keywords = "BRAF, Cetuximab, Colorectal cancer (CRC), Panitumumab, RAS",
author = "Jun Gong and May Cho and Marwan Fakih",
year = "2016",
month = "1",
day = "1",
doi = "10.21037/jgo.2016.06.12",
language = "English (US)",
volume = "7",
pages = "687--704",
journal = "Journal of Gastrointestinal Oncology",
issn = "2078-6891",
publisher = "Pioneer Bioscience Publishing Company (PBPC)",
number = "5",

}

TY - JOUR

T1 - RAS and BRAF in metastatic colorectal cancer management

AU - Gong, Jun

AU - Cho, May

AU - Fakih, Marwan

PY - 2016/1/1

Y1 - 2016/1/1

N2 - The treatment of metastatic colorectal cancer (mCRC) has been further refined with the development of monoclonal antibodies, cetuximab and panitumumab, towards the epidermal growth factor receptor (EGFR). Anti-EGFR therapy has afforded improved survival in those with wild-type RAS mCRC but provides no benefit and even harm in those with RAS-mutant tumors. BRAF mutations have also been shown to predict lack of clinically meaningful benefit to anti-EGFR therapy in mCRC. Mechanisms of resistance to EGFR blockade in wild-type RAS or BRAF metastatic colorectal tumors appear to converge on the mitogen-activated protein kinase (MAPK) signaling pathway. Clinical trials involving combined BRAF, EGFR, and/or MAPK kinase (MEK) inhibition have shown promising activity in BRAF-mutant mCRC. Here, we review pivotal clinical trials that have redefined our treatment approach in mCRC with respect to anti-EGFR therapy based on RAS and BRAF mutation status. Future studies will likely focus on improving efficacy of anti-EGFR-based therapy in mCRC through sustained MAPK pathway inhibition.

AB - The treatment of metastatic colorectal cancer (mCRC) has been further refined with the development of monoclonal antibodies, cetuximab and panitumumab, towards the epidermal growth factor receptor (EGFR). Anti-EGFR therapy has afforded improved survival in those with wild-type RAS mCRC but provides no benefit and even harm in those with RAS-mutant tumors. BRAF mutations have also been shown to predict lack of clinically meaningful benefit to anti-EGFR therapy in mCRC. Mechanisms of resistance to EGFR blockade in wild-type RAS or BRAF metastatic colorectal tumors appear to converge on the mitogen-activated protein kinase (MAPK) signaling pathway. Clinical trials involving combined BRAF, EGFR, and/or MAPK kinase (MEK) inhibition have shown promising activity in BRAF-mutant mCRC. Here, we review pivotal clinical trials that have redefined our treatment approach in mCRC with respect to anti-EGFR therapy based on RAS and BRAF mutation status. Future studies will likely focus on improving efficacy of anti-EGFR-based therapy in mCRC through sustained MAPK pathway inhibition.

KW - BRAF

KW - Cetuximab

KW - Colorectal cancer (CRC)

KW - Panitumumab

KW - RAS

UR - http://www.scopus.com/inward/record.url?scp=85006189459&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006189459&partnerID=8YFLogxK

U2 - 10.21037/jgo.2016.06.12

DO - 10.21037/jgo.2016.06.12

M3 - Review article

AN - SCOPUS:85006189459

VL - 7

SP - 687

EP - 704

JO - Journal of Gastrointestinal Oncology

JF - Journal of Gastrointestinal Oncology

SN - 2078-6891

IS - 5

ER -