Physician-scientists at Sylvester Comprehensive Cancer Center have identified serine/threonine kinase 17a (STK17a) as a novel therapeutic target for glioblastoma and acute myeloid leukemia (AML). The discovery, presented at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, highlights the potential of small molecule inhibitors targeting STK17a in treating these aggressive cancers.
STK17a Overexpression in Glioblastoma and AML
STK17a, a protein involved in cellular stress response, is overexpressed in all glioblastoma patients and a subset of AML patients. This overexpression makes STK17a an attractive target for therapeutic intervention. Researchers, including Dr. Ashish Shah and Dr. Justin Taylor, have been investigating small molecule inhibitors that can selectively target STK17a to disrupt cancer cell growth and survival.
Preclinical Evidence
In AML, Dr. Taylor's team found that STK17a inhibition was particularly effective in patients with the SF3B1 mutation. In cell lines and patient-derived xenograft models, the STK17a inhibitor showed promise in this AML subset. For glioblastoma, Dr. Shah's lab demonstrated that the drug could target a protein overexpressed in brain tumors, hindering cancer cell growth. However, a key challenge remains: ensuring the drug crosses the blood-brain barrier in sufficient concentrations.
Collaborative Research
The discovery exemplifies the power of team science at the University of Miami Miller School of Medicine. Dr. Taylor collaborated with Dr. Yangbo Feng, who synthesized the small molecule inhibitors. By combining expertise in hematology, medicinal chemistry, and neuro-oncology, the researchers were able to identify and validate STK17a as a therapeutic target in multiple cancer types.
Future Directions
Researchers are optimistic about the translational potential of STK17a inhibitors. Dr. Shah estimates that they are two to three years away from initiating clinical trials in patients with glioblastoma. Future studies will focus on toxicology testing and window-of-opportunity trials to assess the drug's ability to penetrate the brain and impact tumor growth. Additionally, the team aims to develop biomarkers to predict patient response to STK17a inhibitors, paving the way for personalized treatment strategies.
Precision Oncology Implications
"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. This approach aligns with the principles of precision oncology, where treatments are tailored to individual patients based on the molecular characteristics of their tumors.
