The Egrf Receptor Inhibitor Erlotinib, Alone Or In Combination With The Rexinoid Lg100268, Is Effective For Prevention In Mouse Models Of Lung And Pancreatic Cancer With Kras Mutations

Lung cancer and pancreatic cancer are leading causes of cancer deaths, with extremely poor 5 year survival rates for both types of cancer. The epidermal growth factor receptor (EGFR) and its ligands regulate cell growth, and EGFR expression is frequently elevated in lung and pancreatic cancer. Tumors with activating mutations in EGFR are treated clinically with drugs such as erlotinib, a tyrosine kinase EGFR inhibitor. Up to 90% of pancreatic cancers and 35% of lung cancers contain activating mutations in Kras, but tumors with Kras mutations are usually resistant to EGRF inhibitors. Erlotinib is an approved drug for treating pancreatic cancer, but it only extends survival by a few weeks. We have previously shown that the rexinoid LG100268 (268) is effective for prevention of experimental lung and pancreatic cancers with Kras mutations, and a recent clinical trial suggests that the combination of a rexinoid and erlotinib might be useful for treating lung cancer, even in tumors with Kras mutations. In order to test whether this combination of drugs might be useful for prevention of lung cancer, female A/J mice were injected i.p. with vinyl carbamate (16 mg/kg) once a week for two weeks. The carcinogen induces Kras mutations and microscopic adenocarcinomas in the lungs within 4-6 weeks. Starting one week after the last injection of carcinogen, the mice were fed the rexinoid 268 (40 mg/kg diet), erlotinib (150 mg/kg diet) or the combination for 16 weeks. All 3 groups significantly (P Citation Format: Karen T. Liby, Charlotte R. Williams, Renee Risingsong, Michael B. Sporn, Ryan M. Collins, Darlene B. Royce. The EGRF receptor inhibitor Erlotinib, alone or in combination with the rexinoid LG100268, is effective for prevention in mouse models of lung and pancreatic cancer with Kras mutations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-245. doi:10.1158/1538-7445.AM2014-LB-245