PT  - JOURNAL ARTICLE
AU  - Yaeger, Rona
AU  - Corcoran, Ryan B.
TI  - Targeting Alterations in the RAF–MEK Pathway
AID  - 10.1158/2159-8290.CD-18-1321
DP  - 2019 Mar 01
TA  - Cancer Discovery
PG  - 329--341
VI  - 9
IP  - 3
4099  - http://cancerdiscovery.aacrjournals.org/content/9/3/329.short
4100  - http://cancerdiscovery.aacrjournals.org/content/9/3/329.full
SO  - Cancer Discov2019 Mar 01; 9
AB  - 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 BRAFV600 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.Significance: Alterations in the RAF and MEK genes represent promising therapeutic targets in multiple cancer types. However, given the unique and complex signaling biology of the MAPK pathway, the diverse array of RAF and MEK alterations observed in cancer can possess distinct functional characteristics. As outlined in this review, understanding the key functional properties of different RAF and MEK alterations is fundamental to selecting the optimal therapeutic approach.