Sylvester Physician-Scientists Find New Target for Cancer Treatment
Article Summary
- The discovery of protein STK17a, overexpressed in all patients with glioblastoma brain tumors and some patients with acute myeloid leukemia, offers a new target for small molecule inhibitors.
- Dr. Ashish Shah and Dr. Justin Taylor presented the discovery at the recent EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.
- Both doctors credit the Miller School of Medicine’s team science, collaborative approach as significant to their discoveries.
Physician-scientists Ashish H. Shah, M.D., and Justin Taylor, M.D., are working toward a scientific breakthrough in cancer treatment that would offer new hope to glioblastoma and acute myeloid leukemia (AML) patients.
Their discovery of protein STK17a, overexpressed in all patients with glioblastoma brain tumors and some patients with acute myeloid leukemia, offers a new target for drugs called small molecule inhibitors. The researchers, working together at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, have been testing these new drugs in their respective labs. They recently presented their findings in Barcelona at the prestigious EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.
Two of their Ph.D. students in the Sheila and David Fuente Graduate Program in Cancer Biology, Jesus “Ray” Castro and Avni Bhalgat, co-authored the paper and also presented.
The symposium, organized by the European Organisation for Research and Treatment of Cancer, the National Cancer Institute and the American Association for Cancer Research, draws academic investigators and representatives from top pharmaceutical companies.
“It is an honor to be selected to present our research on an international stage,” said Dr. Taylor, an associate professor in the Miller School Division of Hematology.
He explained that the AACR meeting offers a venue to share science and gauge interest, and maybe find partnerships with pharmaceutical companies that can transition lab discoveries for the clinical space.
“We have a drug that can target brain tumors, and we want to finish toxicology studies and do a window-of-opportunity trial to see if this drug is able to get into the brain,” said Dr. Shah, an assistant professor of neurological surgery at the Miller School.
A Molecule of an Idea
Dr. Taylor, a hematologist who studies treatments for leukemia, began testing small molecule inhibitors in his lab in collaboration with Yangbo Feng, Ph.D., associate director of medicinal chemistry in the Department of Molecular and Cellular Pharmacology at the Miller School.
Dr. Taylor’s team tested the STK17a inhibitor in cell lines and a patient-derived xenograft model and found the drug showed promise in a subset of AML patients. He said patients with the SF3B1 mutation highly express STK17a, the target of the drug.
Because the drug would only work in a specific subset of people with the disease, Dr. Taylor and his colleagues turned to data from The Cancer Genome Atlas. This landmark genomics program sequenced and molecularly characterized a large variety of cancers. The search for other cancers that highly express STK17a pointed to glioblastoma, the most common brain tumor in adults, and one with no cure and a survival rate of less than two years.
A partnership was born. Dr. Shah began tests in his lab and realized that the drug could target a protein overexpressed in brain tumors, hampering the cancer cells from growing. While this is significant, the challenge with glioblastoma is that the drug needs to cross the blood-brain barrier in high concentrations.
“The translational potential for this is very high,” Dr. Shah said. “We are two to three years away from trying it on patients.”
The doctors stand at the cutting edge of precision oncology.
“It could be that, in the future, we develop a biomarker that can directly or indirectly predict response to this STK17a inhibitor by measuring STK17a expression levels in patients,” Dr. Taylor said.
Team Science
As they continue to realize the cross-potential of their discovery, the researchers appreciate how the team science culture central to the Sylvester Comprehensive Cancer Center and across the university has led them to success.
“I’ve been very fortunate to have collaborators here at Sylvester and UM who are readily available and who leverage their different skill sets so we can get our translational discoveries up in a quick fashion,” Dr. Shah said. “In a silo, you can’t do anything by yourself.”
Tags: Acute Myeloid Leukemia, cancer research, Dr. Ashish Shah, Dr. Justin Taylor, Dr. Yangbo Feng, glioblastoma research, glioblastomas, Leukemia, Sylvester Comprehensive Cancer Center