Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Apr;2(4):336-46.
doi: 10.18632/oncotarget.262.

Potential therapeutic strategies to overcome acquired resistance to BRAF or MEK inhibitors in BRAF mutant cancers

Ryan B Corcoran  1 , Jeffrey Settleman, Jeffrey A Engelman
Affiliations
Review

Potential therapeutic strategies to overcome acquired resistance to BRAF or MEK inhibitors in BRAF mutant cancers

Ryan B Corcoran et al. Oncotarget. 2011 Apr.

Abstract

Recent clinical trials with selective inhibitors of the BRAF and MEK kinases have shown promising results in patients with tumors harboring BRAF V600 mutations. However, as has been observed previously with similarly successful targeted therapies, acquired resistance to these agents is an emerging problem that limits their clinical benefit. Several recent studies from our laboratory and others have investigated the causes of acquired resistance to BRAF and MEK inhibitors, and multiple resistance mechanisms have been identified. Here, we review these mechanisms and suggest that they can be broadly grouped into two main classes: ERK-dependent and ERK-independent. We also propose distinct therapeutic strategies that might be employed to overcome each class of acquired resistance..

PubMed Disclaimer

Figures

Figure 1
Figure 1. Mechanisms of acquired resistance to BRAF and MEK inhibitors in BRAF mutant cancers
A schematic of the RAF-MEK-ERK signaling pathway is shown with BRAF in red. Alterations of signaling pathway components leading to resistance to BRAF or MEK inhibitors are indicated by number. Resistance mechanisms classified as ERK-dependent are shown in the left panel, and mechanisms classified as ERK-independent are shown in the right panel.
See this image and copyright information in PMC

References

    1. Montagut C, Settleman J. Targeting the RAF-MEK-ERK pathway in cancer therapy. Cancer Lett. 2009;283:125–34. - PubMed
    1. Young A, Lyons J, Miller AL, Phan VT, Alarcón IR, McCormick F. Ras signaling and therapies. Adv Cancer Res. 2009;102:1–17. - PubMed
    1. Yoon S, Seger R. The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors. 2006;24:21–44. - PubMed
    1. Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer. 2003;3:459–65. - PubMed
    1. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54. - PubMed

MeSH terms

Substances