Lung cancer represents the most frequent form of malignancy comprising about 25% of all cancer clinical cased worldwide and being one of few cancer types with steadily increasing occurence. Non-small cell lung carcinomas (NSCLC) are proven to be challenging tumor type for clinical management with frequent re-occurence of drug resistant cancer after initial surgery/therapy and prominent metastatic potential. To gain in-depth insight into the molecular basis of lung carcinoma formation and reasons for drug resistance in relapse phase, the Center for Advanced Preclinical Research successfully adopted and characterized several models of NSCLC. We recently completed studies with a Biotechnology Company that established the utility of their irreversible EGFR inhibitor in the regression of LA harboring the primary L858R EGFR mutant present in patient cancers and of those resistant to first line therapy that express the L858RT790 mutant. This drug has shown similar promise in clinical trials. We completed preclinical studies of a proprietary agent, including PK/PD/Tox and efficacy evaluation, in collaboration with a pharmaceutical company.
Walter, Annette O; Sjin, Robert Tjin Tham; Haringsma, Henry J et al. (2013) Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC. Cancer Discov 3:1404-15 |
Walrath, Jessica C; Hawes, Jessica J; Van Dyke, Terry et al. (2010) Genetically engineered mouse models in cancer research. Adv Cancer Res 106:113-64 |