The PI3K network normally promotes cell survival, growth and protein synthesis. When it is abnormally activated by genetic aberrations, it contributes to tumor progression, connects to other cancer-causing pathways and causes resistance to treatment.
The team will use its combined cell line studies, animal model research and data from drugs that have completed phase I clinical trials to identify potential biomarkers - specific genetic mutations in patients' tumors, for example - that will indicate whether a drug will work for specific groups of patients.
Clinical trials of the targeted drugs also will test the validity of candidate biomarkers. Mills, who also directs the Kleberg Center for Molecular Markers at M. D. Anderson, expects the first phase II clinical trial, for endometrial cancer, to open in about six months.
Mills leads the team's tumor cell line and screening core, which will analyze every tumor sample to detect cancer-related genetic mutations, study the effect of genetic aberrations on the PI3K pathway and on PI3K inhibitors used in clinical trials, and identify drug combinations to block the pathway and biomarkers related to those drugs.
Combinations will likely be needed both to stifle the PI3K pathway and to inhibit a second interacting pathway, the MAPK/RAS network. Early cell line and animal model evidence suggest both pathways must be blocked to effectively treat the three cancers.
Also on the Dream Team from M. D. Anderson are Donald Berry, Ph.D., head of the Division of Quantitative Biology; Cheryl Lyn Walker, Ph.D., professor in
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center