Stand Up To Cancer Funded Research Dream Team Takes Aim At Women’s Cancers

Stand Up To Cancer (SU2C), the Entertainment Industry Foundation’s charitable initiative supporting groundbreaking research aimed at getting new cancer treatments to patients in an accelerated timeframe, has reached a significant milestone, awarding the first round of three-year grants — that total $73.6 million — to five multi-disciplinary, multi-institutional research Dream Teams. … Each Dream Team’s project, funded for three years pending satisfactory achievement of stated milestones, is “translational” in nature, geared toward moving science from “bench to bedside” where it can benefit patients as quickly as possible. …

A Dream Team of leading cancer researchers will accelerate development of drugs to attack a mutated [PI3K] molecular pathway that fuels endometrial, breast and ovarian cancers, funded by a three-year $15 million grant awarded today by [SU2C] … Genetic aberrations in the network, known as the PI3K pathway, are found in half of all breast cancer patients, 60 percent of all cases of endometrial cancer and 20 percent of ovarian cancer patients. Other cancers that include a mutationally activated PI3K pathway include melanoma, colon and prostate cancers, brain tumors, and leukemia.

Stand Up To Cancer Awards $73.6 Million For Novel, GroundBreaking Cancer Research

May 27, 2009, New York, NY / Los Angeles, CA:  Stand Up To Cancer (SU2C), the Entertainment Industry Foundation‘s charitable initiative supporting groundbreaking research aimed at getting new cancer treatments to patients in an accelerated timeframe, has reached a significant milestone, awarding the first round of three-year grants — that total $73.6 million — to five multi-disciplinary, multi-institutional research Dream Teams. The majority of these funds were raised in connection with an SU2C telecast on September 5, 2008 that aired simultaneously on the ABC, CBS and NBC networks. Today’s announcement comes on the one-year anniversary of the launch of Stand Up To Cancer. SU2C’s next round of funding — Innovative Research Grants for individual investigators — will be announced later this year. …

Each Dream Team’s project, funded for three years pending satisfactory achievement of stated milestones, is “translational” in nature, geared toward moving science from “bench to bedside” where it can benefit patients as quickly as possible. SU2C’s distinctive funding model was specifically designed to eliminate barriers that can inhibit creativity and collaboration, in part, by enabling scientists with different expertise from different institutions across the country — and in some cases, internationally — to work together. The five Dream Teams are comprised of 7 leaders, 4 co-leaders and 27 principal researchers from over 20 leading institutions, with more than 300 individuals participating in total. Each team will have at least two members from patient advocacy groups to ensure that the perspective of the patients and survivors they represent will be integrated into the research on an ongoing basis.

Five SU2C Dream Team Grants

The teams are listed below in alphabetical order according to the name of the leaders, and they will pursue the following important topics:

• “Bringing Epigenetic Therapy to the Forefront of Cancer Management” / Leader: Stephen B. Baylin, M.D., Deputy Director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Co-Leader: Peter A. Jones, Ph.D., Distinguished Professor of Urology and Biochemistry & Molecular Biology, University of Southern California [Learn more about this project];

• “Targeting the PI3K Pathway in Women’s Cancers” / Leader: Lewis C. Cantley, Ph.D., Chief of the Division of Signal Transduction at Beth Israel Deaconess Medical Center; Co-Leaders: Charles L. Sawyers, M.D., Director of the Human Oncology and Pathogenesis Program at Memorial Sloan-Kettering Cancer Center, and Gordon B. Mills, M.D., Ph.D., Chair, Department of Systems Biology, University of Texas M. D. Anderson Cancer Center [Learn more about this project];

• “An Integrated Approach to Targeting Molecular Breast Cancer Molecular Subtypes and Their ‘Resistance’ Phenotypes” / Leaders: Joe W. Gray, Ph.D., Life Sciences Division Director, Lawrence Berkeley National Laboratory, and Dennis J. Slamon, M.D., Ph.D., Director of Clinical/Translational Research at UCLA’s Jonsson Comprehensive Cancer Center [Learn more about this project];

• “Bioengineering and Clinical Applications of Circulating Tumor Cells Chip” / Leader: Daniel A. Haber, M.D., Ph.D., Director of the Massachusetts General Hospital Cancer Center; Co-Leader: Mehmet Toner, Ph.D., Professor of Biomedical Engineering, Harvard Medical School [Learn more about this project]; and

• “Cutting off the Fuel Supply: A New Approach to the Treatment of Pancreatic Cancer” / Leaders: Craig B. Thompson, M.D., Director, Abramson Cancer Center at the University of Pennsylvania, and Daniel D. Von Hoff, M.D., Senior Investigator and Physician in Chief at the Translational Research Genomics Institute (TGen) [Learn more about this project].

The projects address some of the most critical and promising areas of cancer research today. They will enable scientists to gain new understanding of the molecular pathways and genetic mutations that contribute to the causes of many cancers; to apply nanotechnology to isolate and analyze circulating tumor cells; to explore imaging approaches that could lead to “starving” tumors; to leverage the growing understanding of epigenetics to design targeted anticancer agents; and to explore new approaches to treating breast cancers, especially those resistant to current therapies. This unique translational research model focuses on the disease, drug targets and clinical development, combining research and clinical applications that have extraordinary potential for patients. …

The First SU2C Dream Teams

M. D. Anderson, Harvard & Memorial-Sloan-Kettering To Target the PI3K Molecular Pathway  In Women’s Cancers

A Dream Team of leading cancer researchers will accelerate development of drugs to attack a mutated molecular pathway that fuels endometrial, breast and ovarian cancers, funded by a three-year $15 million grant awarded today by [SU2C] …

“The pathway involved here is the most common abnormally activated pathway in all of cancer,” said Gordon Mills, M.D., Ph.D., professor and chair of M. D. Anderson’s Department of Systems Biology and a co-leader on the project with two other scientists. “What we learn in women’s cancers will apply to many other types.”

Genetic aberrations in the network, known as the PI3K pathway, are found in half of all breast cancer patients, 60 percent of all cases of endometrial cancer and 20 percent of ovarian cancer patients. Other cancers that include a mutationally activated PI3K pathway include melanoma, colon and prostate cancers, brain tumors, and leukemia.

A variety of drugs under development target different aspects of the complex pathway, which Mills describes as a “target-rich environment.”

“Our major goal is to determine which patients are most likely to benefit from these drugs, so that we get the right therapy to the right patient the first time,” he said. “By the end of three years we are expected to have changed the way in which we manage patients. That’s a very large challenge.”

Dream Team collaborators with Mills are project leader Lewis C. Cantley, Ph.D., chief, division of signal transduction, Cancer Center at Beth Israel Deaconess Medical Center and professor of systems biology at Harvard Medical School, and co-leader Charles Sawyers, M.D., director, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center in New York. The Dream Team also includes research groups at Vanderbilt-Ingram Cancer Center, Vall d’Hebron Oncology Research Institute in Barcelona, and Herbert Irving Comprehensive Cancer Center at Columbia University.

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 the Department of Carcinogenesis and the co-director of M. D. Anderson’s Gynecology Specialized Program in Research Excellence; and Russell Broaddus, M.D., Ph.D. associate professor in the Department of Pathology.

Clinical trials will be based at M. D. Anderson. The endometrial trials will be led by Karen Lu, M.D., and Robert Coleman, M.D., both professors, with Bryan Hennessy, M.D., assistant professor, all of the Department of Gynecologic Medical Oncology. Funda Meric-Bernstam, M.D., associate professor in the Department of Surgical Oncology, will be coordinator of clinical trials as well as leader of the breast cancer trials, working with Ana Gonzalez-Angulo, M.D., associate professor of breast medical oncology. …

M.D. Anderson Cancer Center’s Dr. Gordon Mills on Stand Up to Cancer/ Dream Team Grant

PI3K/AKT Pathway and Cancer

Sources (Quoted):

• Stand Up To Cancer Awards $73.6 Million For Novel, GroundBreaking Cancer Research, Press Release, StandUp2Cancer.org., May 27, 2009.

• Dream team targets key driver for breast, ovarian, endometrial cancers – Stand Up to Cancer funds joint effort by M. D. Anderson, Harvard, Memorial-Sloan-Kettering, News Release, The University of Texas, M.D. Anderson Cancer Center, May 27, 2009.