Breakthrough in Identifying and Targeting Mysterious Bladder Cancer Subtype

Scientists at UCSF have identified new markers on aggressive bladder cancer cells, paving the way for targeted immunotherapy options, including CAR-T therapy, to improve outcomes for patients with previously hard-to-treat tumors.
Researchers at the University of California, San Francisco have achieved a significant advancement in understanding and potentially treating a rare and aggressive form of bladder cancer that has traditionally eluded effective therapies. This particular subtype, often excluded from clinical trials due to its diverse appearance, accounts for up to 25% of bladder cancer cases.
The team discovered a surface marker on tumor cells resembling markers found in ovarian cancer. Specifically, they identified CA125, a protein previously associated mainly with ovarian tumors. Additionally, they uncovered the presence of the protein TM4SF1 on the surface of these bladder cancer cells. Leveraging this discovery, scientists engineered immune cells with CAR-T technology to target TM4SF1, successfully destroying tumors in mouse models, indicating a promising path toward immunotherapy.
The study utilized innovative gene sequencing techniques on single-cell samples from patients to analyze tumor cell populations. Findings revealed that most of the aggressive bladder tumors contained CA125-expressing cells, unlike conventional bladder tumors. This discovery provides a new biomarker for identifying these tumors, which could lead to more personalized and effective treatments.
According to Dr. Sima Porten, associate professor of urology at UCSF, these novel markers could revolutionize how these tumors are diagnosed and treated. Franklin Huang, MD, Ph.D., a co-senior author, emphasized that this approach could finally offer hope for patients with limited options, moving beyond conventional surgery to targeted immunotherapy.
Published in Nature Communications, this breakthrough opens doors for further clinical research and trials. It holds the promise of developing new therapies specifically aimed at these resistant tumors, which frequently recur and worsen patient outcomes. The researchers stress the importance of this discovery as a step forward in combating a challenging subset of bladder cancer that has long been underserved in cancer research.
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