Resistance & sensitivity to molecularly targeted therapies

Two world-renown cancer experts, Drs. George Demetri and Pasi Jänne, from the Dana-Farber Cancer Institute and the Harvard Cancer Center, will present fast-breaking news in a live dialog broadcast over the internet. This webinar will present and update the findings from work published in Science¹ that focuses on a mechanism of resistance to EGFR inhibitors. Evidence from studies of kinase inhibitors such as imatinib (Gleevec) and sunitinib (Sutent) in GIST and other solid tumors will be presented that define how cancer cells evade molecularly targeted therapies.

Tyrosine kinase inhibitors (TKIs), an emerging class of anticancer therapies, such as gefitinib (Iressa) and erlotinib (Tarceva), inhibit the epidermal growth factor receptor (EGFR) kinase and are used to treat non-small cell lung cancers (NSCLCs), while selective kinase inhibitors (imatinib [Gleevec] or nilotinib [Tasigna]) and multi-targeted kinase inhibitors (sunitinib [Sutent]) are used to treat GIST. While most NSCLC or GIST lesions with mutant kinases intitally respond to these inhibitors, the majority of these tumors will ultimately become resistant to targeted drug treatment. The mechanisms that contribute to resistance in at least 50% of NSCLC tumors are unknown, while resistance is understood in more than 70% of GIST cases at a defined molecular level. Pasi Janne, M.D., Ph.D. at the Dana-Farber Cancer Institute and Harvard Cancer Center is investigating the role of MET signaling in NSCLC, CML, and GI Stromal Tumors.

The findings reported in Science₁ show increased MET signaling underlies acquired resistance to gefitinib and that MET inhibition suppresses growth of resistant cells. These results have important clinical implications for NSCLC patients who develop acquired resistance to gefitinib or erlotinib. Their findings also suggest that irreversible EGFR inhibitors, which are currently under clinical development as treatments for patients whose tumors have developed acquired resistance to gefitinib and erlotinib, may be ineffective in the subset of tumors with a MET amplification. Therefore, this important work highlights that, in the future, combination therapies with MET kinase inhibitors, which are in early stage clinical trials, and irreversible EGFR inhibitors could be considered for patients whose tumors have become resistant to EGFR kinase inhibitors. The work of Dr. Demetri and his team complements this work by understanding the mechanisms of continuing evolution of new resistance mutations in GIST cells under the selection of kinase inhibitor drugs.

The official language of this webinar is English.

This webinar with Q&A was recorded on December 14, 2007.

There is no fee to register.  If you wish to receive continuing education credit, there will be a $15.00 USD administrative fee to process your certificate.

¹Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N,Gale CM, Zhao X, Christensen J, Kosaka T, Holmes AJ, Rogers AM, Cappuzzo F, Mok T, Lee C, Johnson BE, Cantley LC, Janne PA. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007; 316(5827):1039-43.