This project focuses on frequent mutations that occur in a set of genes that regulate the PI3K pathway, which is a complex signaling cascade that, in concert with other signaling networks, regulates cell survival and growth. The scientists involved in this Dream Team are the pioneers who discovered the PI3K pathway and validated its role in human cancers, and they will focus on breast, ovarian and endometrial cancers, all of which have the PI3K mutation.
A number of drugs to inhibit this pathway have been developed and currently are in clinical trials. However, as with other "targeted" therapies, only a fraction of patients who enroll in these trials benefit, and it is not possible to predict which patients will respond positively. This means that many women will be given treatments that have no benefit to them or could cause unnecessary complications.
The goal of this Dream Team is to discover approaches that will predict which patients will respond positively to PI3K inhibitors. If successful, this will accelerate personalized cancer treatment that can be incorporated into standard practice. Specific Research Goals
The PI3K pathway is mutated in more cancer patients than any other, and these mutations are the most frequent events in women's cancers, making it an attractive molecular target for agents that inhibit these genetic aberrations. If successful, this project will allow clinicians to use biomarkers and imaging techniques to predict which patients will benefit from PI3K pathway inhibitors and lead to the development of therapeutic combinations that will hit multiple targets in the complex pathways that contribute to cancer cell growth.
This work will help assure that these therapies are given to patients who will benefit from them, and it will also increase the overall pace of clinical trials targeting PI3K inhibitors.
This SU2C Dream Team has pooled resources from seven major cancer centers to survey thousands of breast, ovarian and endometrial cancers to look at a group of genes involved in cell growth. These genes make up an information pathway that, when broken, can allow cells to grow uncontrollably. The team is enrolling patients with these phosphoinositide PI3-kinase (PI3K) mutations into clinical trials to test combinations of drugs to attack multiple problems with breast, ovarian and endometrial cancers. The team uses biomarkers to decide which combination of drugs will best treat the individual patients. Visit the "Targeting the PI3K Pathway in Women's Cancers" Dream Team website.
Carlos L. Arteaga, MD, director, Vanderbilt Breast Cancer Program, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University
José Baselga, MD, PhD, associate director, MGH Cancer Center; chief, hematology/oncology, medicine, Massachusetts General Hospital
Matthew Maurer, MD, assistant professor, Herbert Irving Comprehensive Cancer Center, Columbia University
Thomas M. Roberts, PhD, co-chair, department of cancer biology, Dana-Farber Cancer Institute
David B. Solit, MD, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center