Repurposed Diabetes Drug Revolutionizes Bladder Cancer Treatment
In an ambitious step toward revolutionizing cancer treatment, UCSF researchers have ingeniously combined an older class of diabetes drugs with cutting-edge CAR T-cell therapy to potentially transform the landscape of resistant bladder cancer treatment. Urothelial carcinoma (UC), a formidable challenger in the realm of genitourinary cancers, claims over 16,000 lives annually in the U.S. despite advances in therapeutic approaches. With metastatic UC’s discouraging survival rate of just 5% to 10%, the need for ingenious strategies has never been more pressing.
Unveiling a New Strategy
The standard bearer for metastatic UC treatment, enfortumab vedotin (EV), has set a commendable response rate of 40% by targeting NECTIN4, a protein heavily associated with bladder cancer. Yet, in cases where resistance stubbornly persists, treatment outcomes often fall short of expectations. To counter this, UCSF scientists led by Jonathan Chou, MD, PhD, meticulously engineered a CAR T-cell therapy, pairing it with thiazolidinediones—diabetes drugs renowned for their PPAR gamma pathway stimulation. This harmonious pairing significantly enhances NECTIN4 expression, thereby amplifying the CAR T-cell therapy’s effectiveness.
Enhancing NECTIN4 Expression
The core of this groundbreaking research lies in understanding NECTIN4 regulation within cancer cells. “We sought to understand how cancer cells regulated expression of NECTIN4, and whether we could leverage that information to enhance NECTIN4 expression and increase the efficacy of the CAR T therapy,” remarked Dr. Chou. According to Technology Networks, older diabetes medications like rosiglitazone and pioglitazone were masterfully repurposed for this mission, proving successful in stimulating the PPAR gamma pathway and boosting NECTIN4 expression.
Promise in Resistant Cases
A remarkable advantage of this approach is its efficacy in previously resistant tumors. Collaborating with experts like Carissa Chu, MD, and partners at Memorial Sloan Kettering Cancer Center, the UCSF team diligently examined the nuances of NECTIN4 expression in biopsies. By priming tumors with rosiglitazone, they observed considerable efficiency gains in the NECTIN4 CAR T-cell therapy within both cell line and animal models. Dr. Chou summarized the significance, stating, “These preclinical results lay the groundwork for further CAR T cell development in bladder cancer and urothelial carcinomas and suggest drug combinations that will expand the therapeutic window of NECTIN4-targeting therapies.”
A Promising Horizon
This innovation not only opens up new therapeutic avenues for those battling bladder cancer but also invites a reflective consideration of repurposing available treatments to combat other resistant cancers. As this study suggests, the synergy of established diabetes drugs and advanced cancer therapies could herald a new era in oncological care. With ongoing research and clinical trials on the horizon, UCSF leads the charge toward an enhanced quality of life for those confronting one of the toughest cancers.
