KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib.
BACKGROUND
Somatic mutations in the gene for the epidermal growth factor receptor (EGFR) are found in adenocarcinomas of the lung and are associated with sensitivity to the kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Lung adenocarcinomas also harbor activating mutations in the downstream GTPase, KRAS, and mutations in EGFR and KRAS appear to be mutually exclusive.


RESULTS
We sought to determine whether mutations in KRAS could be used to further enhance prediction of response to gefitinib or erlotinib. We screened 60 lung adenocarcinomas defined as sensitive or refractory to gefitinib or erlotinib for mutations in EGFR and KRAS. We show that mutations in KRAS are associated with a lack of sensitivity to either drug.


CONCLUSIONS
Our results suggest that treatment decisions regarding use of these kinase inhibitors might be improved by determining the mutational status of both EGFR and KRAS.
Pao
William
W
Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. paow@mskcc.org
Wang
Theresa Y
TY
Riely
Gregory J
GJ
Miller
Vincent A
VA
Pan
Qiulu
Q
Ladanyi
Marc
M
Zakowski
Maureen F
MF
Heelan
Robert T
RT
Kris
Mark G
MG
Varmus
Harold E
HE
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D003657:Decision Making; D019008:Drug Resistance, Neoplasm; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D011799:Quinazolines / Q000494:pharmacology*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib