SU2C, MRA announce new Dream Team dedicated to melanoma research

American Association for Cancer ResearchDec 15 2011

Team will pursue targeted therapies for patients with a melanoma subtype for which there are few treatment options

Stand Up To Cancer (SU2C), the Melanoma Research Alliance (MRA) and SU2C's scientific partner, the American Association for Cancer Research (AACR), today announced a new Dream Team dedicated to melanoma research. Jeffrey M. Trent, Ph.D., and Patricia M. LoRusso, D.O., will lead the Dream Team project entitled "Personalized Medicine for Patients with BRAF Wild-Type (BRAFwt) Cancer."

Melanoma of the skin is the fifth most common cancer diagnosed in the United States, where one person dies from the disease every hour.

"Having a Dream Team of physicians and scientists focus on such an important and unmet need for patients who are not able to benefit from the latest breakthrough drugs is a most welcome development," said Debra Black, co-founder and chair of the Melanoma Research Alliance. "MRA's joining with Stand Up To Cancer and the AACR to fund such a talented and committed team marks an event of great significance that could herald the next wave of discoveries for patients and all those at risk for being diagnosed with this deadly skin cancer."

"Combining resources to compete against this disease and accelerating the pace of cancer research are twin pillars of the Stand Up To Cancer approach, and we were delighted to work with the Melanoma Research Alliance on our first grant made in collaboration with another foundation," said Sherry Lansing, one of Stand Up To Cancer's co-founders. "Another exciting first is having Dr. LoRusso as the first woman among SU2C's Dream Team leaders and co-leaders."

Trent, an internationally recognized expert in molecular-based systems biology approaches to cancer, will serve as Dream Team leader. He is president and research director at the Translational Genomics Research Institute (TGen) in Phoenix, Az., where he is also professor in the genetic basis of human disease division and head of the melanoma therapeutics lab. He also holds a similar title at the Van Andel Research Institute. His work is focused on applying genomic tools to study melanoma, and he is recognized for this work and his work in translational medicine.

LoRusso, Dream Team co-leader, is director of the Eisenberg Center for Experimental Therapeutics, principal investigator for the Barbara Ann Karmanos Cancer Institute's National Cancer Insitute-UO1-funded phase I program, and professor of oncology at Karmanos Cancer Institute and Wayne State University School of Medicine in Detroit, Mich. She is a leading clinical investigator in early developmental therapeutics and will be principal investigator for the clinical trials, overseeing all clinical aspects of this Dream Team project.

The SU2C-MRA Melanoma Dream Team Translational Cancer Research Grant provides $6 million during a three-year period. The project is intended to accelerate the application of new therapeutic agents to the clinic, thus advancing scientific research in the interests of both today's cancer patients and those who may develop cancer in the future.

"The Stand Up To Cancer-Melanoma Research Alliance grant gives us the remarkable ability to align cutting edge researchers across the globe to join forces to defeat this terrible disease," said Trent.

"We hope to use this unique multi-stage clinical investigation to define new treatments that will produce benefits for metastatic melanoma patients, based on extensive genomic profiling. We have great scientists and clinicians from across the nation who will join forces on this," said LoRusso.

Currently, patients who develop metastatic melanoma have a dismal prognosis, with a median survival of six to nine months and a three-year survival rate of 10 percent to 15 percent. About half of patients with metastatic melanoma have an oncogenic mutation in their tumor's BRAF gene, but the other half of patients are BRAF wild type (BRAFwt) and have no mutation in the gene. Very little progress has been made to identify new therapeutic targets to treat patients with BRAFwt metastatic melanoma.

This Dream Team will investigate the utility of personalized target/therapy identification in patients with BRAFwt metastatic melanoma and will explore the efficacy of molecularly guided therapy involving numerous Food and Drug Administration-approved and investigational agents. Team members will molecularly profile BRAFwt and BRAF-mutant cell lines and test for sensitivity to 100 prioritized compounds that might translate into therapeutic utility. Researchers will use these data to generate models that predict the sensitivity of BRAFwt melanomas to specific drugs. They will test these predictions using xenografts of the melanoma cell lines and primary tumors. An ensuing clinical trial will determine whether this personalized approach significantly improves clinical outcome. The goal is a 30-percent improvement in tumor response relative to standard-of-care therapy.

The target for the start of clinical trials is estimated at mid-2012. To inquire about clinical trials, e-mail [email protected].

The team hopes that an individualized medicine approach to the treatment of BRAFwt metastatic melanoma will not only lead to therapeutic benefit for this patient population but may also be beneficial to many other tumor and disease types.

"The collaboration between Trent, an expert in human cancer genetics, and LoRusso, a clinician and clinical trialist, exemplifies the types of expertise SU2C brings together in hoping to move science from bench to bedside where it can benefit patients quickly," said Nobel Laureate Phillip A. Sharp, Ph.D., institute professor at the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology.

Sharp chaired the SU2C-MRA Joint Scientific Advisory Committee (JSAC) in its unique, interactive, rapid and rigorous evaluation of Dream Team applications via a multi-step scientific review process. The committee is composed of highly accomplished senior laboratory researchers and physician-scientists, as well as advocates. JSAC vice chairpersons include Suzanne L. Topalian, M.D., professor of surgery and director of the Melanoma Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, and also Chief Science Officer at the MRA, and William G. Kaelin, Jr., M.D., professor at the Dana-Farber Cancer Institute.

The review process began with a call for ideas issued by the AACR in May, coinciding with National Melanoma Awareness Month. In response, the AACR received 17 submissions, all of which were evaluated by the JSAC members.

The committee then chose three finalist teams, which each met in person with the JSAC to present the plans for their research, and respond to questions about their projects - a level of interaction between applicants and reviewers that is unique in a scientific review process.

Since the launch of SU2C in 2008, the AACR has played an integral role as SU2C's scientific partner by providing expert peer review and grants administration, as well as ongoing scientific oversight to ensure that progress is being made. The AACR will work closely with the MRA, the largest private funder of melanoma research.

"We are very excited about the synergy between the AACR, SU2C and MRA on the first collaborative Dream Team model. The team has great potential for providing new hope for patients with a type of melanoma that is particularly challenging to treat, and for further advancing the field," said Margaret Foti, Ph.D., M.D., (h.c.), chief executive officer of the AACR.

The "Personalized Medicine for Patients with BRAF Wild-Type (BRAFwt) Cancer" Dream Team is composed of a multidisciplinary group including experts in the medical management of patients with metastatic melanoma, drug development, genomics research, biostatistics, bioinformatics and patient advocacy. It includes laboratory and clinical researchers, young investigators and senior scientists who have not worked together in the past, as well as patient advocates. In addition to Trent and LoRusso, team members include:

Principals:

• Svetomir Markovic, M.D., Ph.D., Mayo Clinic
• Brian Nickoloff, M.D., Ph.D., Michigan State University College of Human Medicine
• Neal Rosen, M.D., Ph.D., Memorial Sloan-Kettering Cancer Center
• Nicholas J. Schork, Ph.D., The Scripps Research Institute & Scripps Health
• Aleksandar Sekulic, M.D., Ph.D., Mayo Clinic
• Jeffrey A. Sosman, M.D., Vanderbilt University
• Kristiina Vuori, M.D., Ph.D., Sanford-Burnham Medical Research Institute
• Craig Webb, Ph.D., Van Andel Research Institute
• Joshua LaBaer, M.D., Ph.D., The Biodesign Institute at Arizona State University

Advocates:

• Mark Gorman, J.D., National Coalition for Cancer Survivorship
• Derrick Hall, president of Arizona Diamondbacks MLB League
• Connie Mack, U.S. Senator, Ret.
• Jane Perlmutter, Ph.D., Gemini Group

Dream Team members come from the following institutions: Translational Genomic Research Institute, Karmanos Cancer Institute, Mayo Clinic, Michigan State University College of Human Medicine, Scripps Research Institute & Scripps Health, Van Andel Research Institute, Sanford-Burnham Medical Research Institute, Memorial Sloan-Kettering Cancer Center, Vanderbilt University, Arizona State University, Johns Hopkins University, National Cancer Institute, Queensland Institute for Medical Research, and University of California Santa Cruz.

Prior to today's announcement, SU2C has awarded grants to five Dream Teams comprised of 221 scientists at 43 unique institutions. The 26 Innovative Research Grants that have been awarded to young investigators include the Allan H. (Bud) and Sue Selig Stand Up To Cancer Melanoma Innovative Research Grant to Dr. Roger Lo at UCLA's Jonsson Comprehensive Cancer Center, who is investigating which specific genetic changes lead to drug resistance in some patients with melanoma. MRA, in the four years since its founding, has awarded more than $30 million in funding to 73 projects at 55 institutions in 10 countries.