Also receives major grant from Stand Up to Cancer to “starve cancer cells to death”

Case Western Reserve University School of Medicine and the Case Comprehensive Cancer Center have been named to a new colorectal cancer Dream Team that was announced in April at the annual meeting of the American Association for Cancer Research in Washington, D.C. The Dream Team comprises scientists, clinicians, technicians and other experts from Memorial Sloan Kettering Cancer Center, Yale University, Cornell University and CWRU/Case Comprehensive Cancer Center.

Dream Teams bring together top scientists from different institutions and disciplines to form collaborative research teams that tackle patient care problems in cancer.

It also was announced that as a member of the Dream Team, Case Comprehensive Cancer Center—a partnership of Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center and Cleveland Clinic—will test a promising new therapy for the first time in colorectal cancer patients as part of a grant award from entertainment industry-led Stand Up to Cancer and the American Association for Cancer Research. Under the grant, $12 million will be apportioned among all four institutional team members for several different projects.

In one of these projects, Zhenghe John Wang, professor in the department of genetics and genome sciences at CWRU School of Medicine and co-leader of the GI Cancer Genetics program at Case Comprehensive Cancer Center, will lead a team that will conduct clinical trials and laboratory research to evaluate the effectiveness of combining CB-839, a glutaminase inhibitor, with capecitabine (a chemotherapy medication used to treat colorectal cancer) in colorectal cancer patients whose tumors have mutations in the PIK3CA gene.

“We are honored to be selected for the Dream Team and to receive this prestigious grant award,” said Wang. “We are grateful to both Stand Up to Cancer and the American Association for Cancer Research. In everyday terms, under the grant we will try to starve colorectal cancer cells to death by depriving them of a nutrient they need called glutamine.”

Over a decade ago, Wang co-discovered that there are mutations of the PIK3CA gene (which is critical for cell division and movement) in 20 to 30 percent of colorectal cancers, suggesting that the mutations play a role in the formation of colorectal cancer. Mutations in PIK3CA are also found in other cancers, including breast cancer, raising the prospect of extending potentially successful treatment of colorectal cancer to these other cancers.

Yujun Hao, a postdoctoral fellow in the Wang laboratory, recently discovered that PIK3CA mutations make colorectal cancer cells exceptionally dependent on glutamine, an amino acid that provides fuel (nitrogen and carbon) to the cancer cells. The Wang team found that blocking glutamine utilization in colorectal cancer cells that have PIK3CA mutations, in combination with the chemotherapy drug capecitabine, induced tumor regression in mice. They did not observe the same effect on tumors without the mutations. Now CWRU-linked clinicians will attempt to repeat those findings in human cancer patients.

The human clinical trials, which will be conducted at University Hospitals Cleveland Medical Center and Cleveland Clinic, will be led by Neal Meropol, professor of medicine at CWRU, division chief of hematology and oncology at University Hospitals Cleveland Medical Center, and associate director for clinical research at Case Comprehensive Cancer Center; Jennifer Eads, assistant professor of medicine at CWRU; and Alok Khorana, a medical oncologist at Cleveland Clinic and professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. The clinical trials will be conducted with the support and oversight of Case Comprehensive Cancer Center, led by its director, Stanton Gerson, the Asa and Patricia Shiverick-Jane Shiverick (Tripp) Professor of hematological oncology and director of University Hospitals Seidman Cancer Center.

Other CWRU School of Medicine investigators on the Dream Team include Sanford Markowitz, the Ingalls Professor of cancer genetics and Distinguished University Professor, medical oncologist at University Hospitals Cleveland Medical Center, and co-leader of the GI Cancer Genetics Program at Case Comprehensive Cancer Center; Joseph Willis, professor and vice chair of the department of pathology and chief of pathology at University Hospitals Cleveland Medical Center; Jill Barnholtz-Sloan, the Sally S. Morley Designated Professor in Brain Tumor research and associate director for bioinformatics at Case Comprehensive Cancer Center; and Kishore Guda, assistant professor in the division of general medical sciences-oncology at Case Comprehensive Cancer Center.

The newly announced Dream Team joins Stand Up to Cancer’s 19 other Dream Teams, three of which—and one smaller translational research team—are working to improve detection, diagnosis and treatment of colorectal cancer.

The National Cancer Institute estimates that 4.5 percent of all men and women in the United States will be diagnosed with colorectal cancer during their lifetime, making it the third most common non-skin cancer.