Development of small-molecule therapeutics and strategies for targeting RAF kinase in BRAF-mutant colorectal cancer.

ABSTRACT: RAF kinase is crucially involved in cell proliferation and survival in colorectal cancer (CRC). Patients with metastatic CRC (mCRC) harboring BRAF mutations (BRAFms) not only experience a poor prognosis but also benefit less from therapeutics targeting ERK signaling. With advances in RAF inhibitors and second-generation inhibitors including encorafenib and vemurafenib, which have been approved for treating BRAF-V600E malignancies, the combinatorial therapeutic strategies of RAF inhibitors elicit remarkable responses in patients with BRAF-V600E mCRC. However, the therapeutic efficacy is restricted by resistance, which might be due to RAF dimerization and reactivation of the MAPK pathway. In addition, the next-generation RAF inhibitors, which are characterized by varying structural and bioch

SUBMITTER: Pan JH 

PROVIDER: S-EPMC6078078 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature