Researchers have identified a new potential therapeutic target—the cell-surface tumor antigen CUB domain–containing protein 1 (CDCP1)—for patients with all subtypes of metastatic bladder cancer, according to findings presented by Chopra et al at the Society of Nuclear Medicine & Molecular Imaging (SNMMI) 2023 Annual Meeting (Abstract 1409). The study may lay the groundwork for more effective detection and treatment of the disease.
Background
Bladder cancer, the second most common malignancy of the genitourinary tract, causes over 17,000 deaths in the United States per year. Despite recent U.S. Food and Drug Administration approvals of bladder cancer therapies, metastatic bladder cancer remains incurable, representing an urgent need for new treatments strategies.
“We know that bladder cancer is molecularly heterogeneous and uniformly fatal,” stressed lead study author Shalini Chopra, PhD, a postdoctoral researcher and an assistant specialist in the Department of Radiology at the University of California, San Francisco School of Medicine. “In this research, we investigated … CDCP1 to see whether it [was] a viable target for bladder cancer radiopharmaceutical therapy using radiolabeled anti-CDCP1 antibodies,” she added.
Study Methods and Results
In the study, the researchers evaluated CDCP1 expression in four bladder cancer data sets containing more than 1,000 biopsies. The researchers used immunohistochemistry to determine if CDCP1 was present in the biopsies, and CDCP1 expression was evaluated in patient-derived xenografts and cell lysates by immunoblot, flow cytometry, and saturation binding assays. Tumor detection in mouse bladder cancer models was tested using zirconium (Zr)-89–4A06, a monoclonal antibody capable of targeting CDCP1. Mice were then treated with lutetium (Lu)-177–4A06 to evaluate the antitumor effects.
The researchers discovered that CDCP1 was expressed in 53% of the primary bladder cancer biopsies, with the highest expression observed in the aggressive basal/squamous subtype. Further, Zr-89–4A06 detected five human bladder cancer xenografts and Lu-177–4A06 inhibited the growth of the bladder cancer xenografts as well.
Conclusions
“These data establish for the first time that CDCP1 is expressed in bladder cancer and introduces a new therapeutic target for this common and deadly malignancy,” highlighted Dr. Chopra. “CDCP1-directed therapeutics may add to the current standard of care and improve the survival rate of patients with metastatic bladder cancer. As there are not many nuclear medicine treatments available for bladder cancer, we hope that this research can generate excitement among fellow nuclear medicine researchers to explore the disease and fill existing gaps in treatment,” she concluded.
