Journal
CANCER DISCOVERY
Volume 9, Issue 3, Pages 329-341Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-18-1321
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Funding
- NIH/NCI Gastrointestinal Cancer SPORE [P50 CA127003, R01CA208437, U54CA224068]
- Cancer Center Core grant [P30 CA008748]
- Stand Up To Cancer Colorectal Dream Team Translational Research Grant [SU2C-AACR-DT22-17]
- [R01 CA233736]
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The MAPK pathway is one of the most commonly mutated oncogenic pathways in cancer. Although RAS mutations are the most frequent MAPK alterations, less frequent alterations in downstream components of the pathway, including the RAF and MEK genes, offer promising therapeutic opportunities. In addition to BRAF(V600) mutations, for which several approved therapeutic regimens exist, other alterations in the RAF and MEK genes may provide more rare, but tractable, targets. However, recent studies have illustrated the complexity of MAPK signaling and highlighted that distinct alterations in these genes may have strikingly different properties. Understanding the unique functional characteristics of specific RAF and MEK alterations, reviewed herein, will be critical for developing effective therapeutic approaches for these targets.
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