Resistance to Raf inhibition in cancer.
The use of small molecule BRAF inhibitors has revolutionized the treatment of advanced melanoma. Despite this, resistance is commonplace and associated with a median progression-free survival of >5 months. Major resistance mechanisms include reactivation of the MAPK pathway and increased PI3K/AKT signaling. Here we review some of the combination therapeutic strategies currently undergoing evaluation for the management of acquired drug resistance in melanoma.
H Eirik
HE
Haarberg
Keiran S M
KS
Smalley
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
D019869:Phosphatidylinositol 3-Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt