Dr Petrylak on Emerging Therapeutic Targets in Urothelial Cancer

Daniel Petrylak, MD, professor, medicine, Medical Oncology and Urology, chief, Genitourinary Oncology, Yale School of Medicine, discusses emerging therapeutic targets showing early potential in metastatic urothelial cancer.

Investigators are currently working alongside Flare Therapeutics to develop a PPAR-γ antagonist targeting urothelial carcinomas. This is a promising area of research, as approximately 25% of tumors express this target, Petrylak explains. Selectively targeting a specific subset of urothelial carcinomas that may benefit from PPAR-γ inhibition could also advance precision medicine approaches in urothelial cancer, he adds.

Additionally, novel antibody-drug conjugates (ADCs) such as SLITRK6 are also being developed for different targets in urothelial cancer, Petrylak continues. Although the agent has been developed alongside enfortumab vedotin-ejfv (Padcev), SLITRK6 targets a different epitope on cancer cells that is expressed in about 90% of urothelial cancer cases, Petrylak details. Understanding the mechanisms of action and potential cross-resistance between these ADCs and other therapies like pembrolizumab (Keytruda) is critical for optimizing treatment strategies. Moving forward, sequencing these therapies appropriately will be essential to maximize efficacy and minimize resistance, Petrylak says.

One of the key challenges in this field is deciphering who will benefit most from these novel therapies and how to sequence them effectively, Petrylak emphasizes. In the adjuvant setting, where treatment decisions can have profound implications on patient outcomes, it is crucial to avoid unnecessary treatment by accurately identifying patients who will derive the most benefit from specific interventions, Petrylak states. This requires a deeper understanding of tumor biology and predictive factors that can inform personalized treatment approaches.

Clinical trials that investigate the optimal sequence of treatments and explore potential biomarkers for response are needed to guide clinical decision-making, he adds. Future research efforts should focus on molecularly-driven studies that evaluate different targets and biomarkers to optimize outcomes for patients with urothelial carcinoma, Petrylak concludes.