‘Dream Team’ stands up to melanoma cancer

This unique clinical study will pursue new therapies for a type of melanoma known as BRAF Wild-Type, for which there are few treatment options. Melanoma is the most dangerous form of skin cancer.

Stand Up To Cancer (SU2C) and the Melanoma Research Alliance (MRA) are funding the study, which they announced today along with SU2C’s scientific partner, the AACR.

The SU2C-MRA Melanoma Dream Team Translational Cancer Research Grant provides $6 million for three years. The project is intended to accelerate the application of new therapeutic agents, quickly moving new scientific discoveries to clinics where they can immediately benefit patients. In the United States, nearly 70,000 people are diagnosed with melanoma each year. Someone dies from melanoma every hour – about 8,000 annually.

The study, which will involve nearly 50 scientists and 150 patients at more than a dozen institutes, will be headed by SU2C-MRA Dream Team leaders Jeffrey Trent, president and research director at TGen in Phoenix, and Patricia LoRusso, director of the Eisenberg Center for Experimental Therapeutics at the Karmanos Cancer Institute in Detroit.

“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, an internationally recognized expert in molecular-based systems biology approaches to cancer who will supervise patients’ genetic and genomic sequencing, spelling out their DNA.

“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, who will supervise the selection of patients, tissue samples and clinical trials research.

In Arizona, TGen’s collaborators on the study include Mayo Clinic and ASU’s Biodesign Institute. Also contributing is TGen’s affiliate institute, the Van Andel Research Institute (VARI) in Grand Rapids, Mich.

“This grant provides a tremendous opportunity to apply the recent advances in molecular medicine to treatment of melanoma,” said Aleksandar Sekulic, of the Mayo Clinic in Arizona. “We are thrilled about the possibilities this research will bring to our melanoma patients who have very limited treatment options today.”

“We look forward to participating in this outstanding, multidisciplinary melanoma research Dream Team to identify new therapeutic targets and ultimately translate our research to improve clinical outcomes,” said LaBaer, director of the Virginia G. Piper Center for Personalized Diagnostics at ASU’s Biodesign Institute.

“Our expertise in cell-based assays and proteomics hold promise for making new discoveries to advance our understanding of molecularly guided melanoma therapies and ultimately, improve patient outcomes,” said Meldrum, director of the Biodesign Institute’s Center for Biosignatures Discovery Automation.

“Stand Up to Cancer’s Dream Team approach, and this project in particular, are truly emblematic of the collaborative nature of personalized medicine, in which experts from multiple disciplines converge as a dedicated team to integrate clinical expertise with unprecedented advances in knowledge and technologies, emphasizing the use of genetic information about an individual patient to optimize that patient’s care,” said Craig Webb, co-director of the VARI Pediatric Cancer Translational Research Program.

Other Dream Team institutes involved in the study include: Mayo Clinic campuses in Minnesota and Florida, Michigan State University, Scripps Research Institute, Sanford-Burnham Medical Research Institute, Memorial Sloan-Kettering Cancer Center, Vanderbilt University, Johns Hopkins University, University of California-Santa Cruz, Scottsdale Healthcare, National Cancer Institute, and Queensland Institute for Medical Research.

“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 AACR to field such a talented and committed team marks an event of great significance that could herald a next wave of discoveries for patients and all those at risk of 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 also is a professor in TGen’s Genetic Basis of Human Disease Division and Head of the Melanoma Therapeutics Lab. He also is president and research director at VARI. His work is focused on applying genomic tools to study melanoma, and he is recognized for this as well as his work in translational medicine and will act as the principal investigator overseeing translational research of this Dream Team project.

LoRusso also is a 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. She is a leading clinical investigator in early developmental therapeutics and will act as principal investigator for the clinical trials, overseeing all clinical aspects of this Dream Team project.

The Melanoma Dream Team’s research project

Currently, patients who develop metastatic melanoma have a dismal prognosis, with a median survival of six to nine months and a five-year survival rate of 15 percent to 20 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 metastatic melanoma patients with BRAFwt disease.

This Dream Team will investigate the utility of personalized target/therapy identification in patients with BRAFwt metastatic melanoma. It 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 as well as 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 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.

Dream Team selected through rigorous, interactive process

“The collaboration between Dr. Trent, an expert in human cancer genetics, and Dr. LoRusso, a clinician and clinical trialist, exemplifies the types of expertise Stand Up To Cancer brings together in hoping to move science from bench to bedside where it can benefit patients quickly,” said Nobel laureate Phillip A. Sharp, 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.

Since the launch of Stand Up To Cancer 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. AACR will work closely with MRA, the largest private funder of melanoma research.

Melanoma Dream Team principals and advocate members

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

Advocates:

• Mark Gorman, JD, National Coalition for Cancer Survivorship • Derrick Hall, President, Major League Baseball’s Arizona Diamondbacks • Connie Mack, U.S. Senator, Ret. • Jane Perlmutter, PhD, Gemini Group

Before this announcement, SU2C has funded five Dream Teams comprised of 221 scientists at 43 unique institutions, and has awarded Innovative Research Grants to 26 individual young investigators pursuing high-risk, high-reward research projects unlikely to be funded by traditional sources. MRA, in the three years since its founding, has awarded more than $30 million in funding to 73 projects at 55 institutions in 10 countries.

“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, chief executive officer of the AACR.

This is the second Dream Team grant for TGen. In May 2009, TGen and the University of Pennsylvania received a SU2C grant to study new approaches for treating pancreatic cancer. A video featuring Dr. Trent and Dr. LoRusso is available at: http://www.interdubs.com/r/su2c/filfo/31/68/3168/Melanoma_DT_v8.mov.

For an online video detailing the effort, visit http://www.youtube.com/watch?v=VLRaxFfuuuw.