The Coriell Institute for Medical Research is now participating in a prestigious SU2C Catalyst® grant from Stand Up To Cancer for the study of epigenetic therapy in treating urothelial cancer, a common form of cancer typically found in the bladder. Part of the project grant was moved to Coriell following its hiring of Jean-Pierre Issa, MD, as its new President and Chief Executive Officer.
With support from Genentech, a member of the Roche Group and SU2C Catalyst Charter Supporter, the $2.9 million grant was awarded at the end of 2017 to an SU2C Catalyst® team led by Van Andel Research Institute’s Peter A. Jones, PhD, DSc. The new SU2C Catalyst Urothelial Bladder Cancer Research Team, of which Dr. Issa is a member, is hoping to boost the effectiveness of one of Genentech’s immunotherapy drugs – atezolizumab – used to treat the cancer by training a patient’s immune system to attack the cancerous cells. The majority of urothelial cancer patients, however, are resistant to atezolizumab alone (and treatments like it) and researchers don’t yet understand why.
“Immunotherapies hold exciting promise for the treatment of otherwise stubborn cancers, but they have not reached their full potential,” Dr. Issa said. “By also targeting a patient’s epigenetics in treatment, we hope to help immunotherapies better fulfill that promise.”
The SU2C Catalyst team suggests the medication’s effectiveness can be boosted by modifying the patient’s epigenetic profile, or the turning “on” and “off” of certain genes, by using additional medications. DNA contains the entirety of our genetic code, but most genes are not active – or “on” – at all times.
Genes can be turned on and off for many reasons, one of which is to coordinate the immune system’s response to threats. Cancer cells can hijack this system and trick the body into stopping its attack. Immunotherapy drugs such as atezolizumab work to block that hijacking, keeping these genes active and the immune system focused on eliminating cancerous cells.
The research team suggests that atezolizumab is less effective or stops being effective in some patients because of other factors which suppress the patient’s epigenetic response and that by using drugs that target the epigenome, a patient’s overall response to immunotherapy can be improved.
As part of the study, the team is analyzing gene expression and the epigenetic status of DNA of patients’ immune and tumor cells before and after they are treated to determine if this new drug combination is in fact altering the patients’ epigenetics and bolstering the effectiveness of the immunotherapy.
The study is currently recruiting patients at Fox Chase Cancer Center in Philadelphia, Pennsylvania, University of Southern California in Los Angeles, California, and Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland.
The SU2C Catalyst Team will collaborate with the separate Van Andel Research Institute-Stand Up To Cancer Epigenetics Dream Team, an international collective of leading epigenetics experts which includes Dr. Issa as well, and the clinical and correlative studies of the SU2C Catalyst Team will support the Dream Team’s work.
