Justin Taylor, M.D., an assistant professor with Sylvester Comprehensive Cancer Center at the Miller School of Medicine in the Division of Hematology, is among an elite group of early-career physician scientists who will receive more than $8.4 million in grants to advance their clinical research.
The Doris Duke Charitable Foundation announced the 2021 Clinical Scientist Development Awards revealing the 17 physician scientists who will receive grants of $495,000 over three years to advance their important research and support their transition to independent clinical research careers. The recipients emerged from a rigorous, multistage peer review process involving 254 applicants.
Dr. Taylor, who is also a member of the Cancer Epigenetics Program, will focus his attention on “Investigating Mechanisms of Resistance to Non-Covalent BTK Inhibition in Patients with B-Cell Malignancies.”
“We are studying a new generation of drug that inhibits Bruton Tyrosine Kinase (BTK) in a different manner than the currently approved BTK inhibitors. This new generation inhibitor is more selective for BTK and can overcome one of the main resistance mechanisms to the older generation of inhibitors,” Dr. Taylor said. “This means they are likely to be more effective and have fewer side effects. So far, they look really promising in clinical trials that are currently in Phase 1 and Phase 2.”
Seeking Patients for Clinical Trial
One of the trials is actively recruiting patients at Sylvester Comprehensive Cancer Center who will be treated with Pirtobrutinib, formerly LOXO-305.
“The initial results from this study in patients with chronic lymphocytic leukemia (CLL) were quite remarkable and were published in The Lancet earlier this year,” Dr. Taylor said.
“We are thrilled to congratulate this year’s Clinical Scientist Development Awardees, who rose to the top of a very competitive pool of applicants,” said Sindy Escobar Alvarez, program director for medical research at The Doris Duke Charitable Foundation. “This is an especially great feat when considering the particular variety of pressures the pandemic has imposed upon physician scientists. With recognition of the invaluable insights their interactions with patients bring to clinical research, we are excited to follow these researchers’ work, which — whether pertaining to infectious or genetic diseases, cancers or Alzheimer’s disease — holds the potential to make vital contributions to human health.”
With the grant, Dr. Taylor said his project will continue to look at ways that B-cell malignancies might become resistant to this new generation of BTK inhibitors or what might make certain types of lymphomas more sensitive or resistant to this treatment approach. He explained how he is using single-cell sequencing to study the genetic and non-genetic causes for resistance — how the tumor cells might adapt to survive the drug treatment through mutations in the DNA or changing gene expression. His lab is also using cell line models, structural model predictions and signaling pathway analysis to discover how this is happening on a molecular level.
“In the future, we might predict which patients are likely to develop resistance and treat them with combination therapies, or monitor for early emergence of resistance and add other therapies before it becomes clinically recognized,” Dr. Taylor said.