The role of KRAS mutations in resistance to EGFR inhibition in the treatment of cancer.
The development of EGFR inhibitors has influenced the field of targeted therapeutics significantly. Unfortunately, the benefits of EGFR inhibitors are limited by several mechanisms of drug resistance, which include KRAS mutations. Mutations in this gene result in constitutive activation of the Ras/Raf/MEK/ERK pathway, with loss of EGFR signaling control, rendering inhibitors of EGFR ineffective. Several strategies are being developed to overcome this mechanism of resistance, including MEK inhibitors, Braf inhibitors, Hsp90 inhibitors, K-Ras-directed immunotherapy, mTOR inhibitors and several combination approaches.
Lopez-Chavez
Ariel
A
National Cancer Institute, Medical Oncology Branch, Center for Cancer Research, Building 10, Room 12N226, 10 Center Drive, Bethesda, MD 20892, USA.
Carter
Corey A
CA
Giaccone
Giuseppe
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics
D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins