Han-Mo Koo Seminar Series

Speaker: David B. Solit, M.D.
VAI Host:  Duesbery , Nick, Ph.D.
Speaker Affiliation: Memorial Sloan-Kettering Cancer Center
Speaker Title: Human Oncology and Pathogenesis Program
Date: June 18, 2008
Time: 12:00 PM to 1:00 PM
Location: Van Andel Institute - Tomatis Auditorium

The focus of my laboratory is the development of cancer therapies that target pathways responsible for cancer initiation and progression. I am particularly interested in the study of cancers dependent upon alterations in tyrosine kinase and steroid receptor signaling. In pursuit of this goal, we have established relevant model systems in which changes in a drugs proposed molecular target can be correlated with drug dose, serum level, and anticancer activity. Our hypothesis is that the consequences of pathway inhibition will vary as a function of cell lineage and the complement of mutations within a tumor cells. Therefore, in order to improve the treat of cancer patients, one must understand not only which genetic changes are commonly found within particular tumor types but the mechanisms whereby these genetic alterations support tumor growth, survival, metastasis or other hallmarks of the cancer phenotype.

One focus of the laboratory is understanding the role played by activated Ras and Raf in mediating transformation. The RAS/RAF/MEK/ERK cascade (MAPK pathway) transduces growth factor initiated signals that regulate cell proliferation and survival. Constitutive activation of this pathway is a common event in human tumors and activating mutations in this pathway occur in Ras, B-Raf and upstream receptor tyrosine kinases (RTK) in a mutually exclusive fashion. We find that tumor cells with activating BRAF mutations are selectively sensitivity to MEK inhibition (Solit et al., Nature 2006). Tumors in which MAP kinase is activated by other upstream activating mutations (RAS, RTKs, unknown) are typically less sensitive or resistant to MEK inhibition.

Using pharmacologic and genetic methods, current studies are focused on identifying which downstream effector pathways are most responsible for mediating growth and survival in tumors with Ras and B-Raf mutations. These studies are of interest as selective inhibitors of these downstream pathways are currently being testing in patients at MSKCC and elsewhere. Concurrent mutations that mediate resistance to Raf and MEK inhibitors are also being studied using preclinical model systems and human tumor samples. One goal of such studies is to use the data generated to develop rational combination therapies.

In person attendance.

Van Andel Research Institute
Tomatis Auditorium
333 Bostwick Ave., N.E.
Grand Rapids, Michigan
49503

Online viewing.

Via webcast* at http://media.vai.org/vaichannel2
Windows Media Player version 9 or above and at least 300Kbps of Internet bandwidth will be required.

*Participants viewing this webcast are not currently eligible for CME Accreditation; however, the Michigan State Medical Society is currently reviewing this process

“This activity has been planned and implemented in accordance with the Essential Areas and policies of the Michigan State Medical Society Committee on CME Accreditation through the joint sponsorship of the Grand Rapids Medical Education & Research Center for Health Professions and the Van Andel Research Institute. The Grand Rapids Medical Education & Research Center for Health Professions is accredited by the Michigan State Medical Society Committee on CME Accreditation to provide continuing medical education for physicians. The Grand Rapids Medical Education & Research Center for Health Professions designates this educational activity for a maximum of one Category 1 credit toward the AMA Physician’s Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.”

For more information please contact Laura Holman at (616) 234-5749