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New Radiopharmaceutical Therapy Target Identified for Metastatic Bladder Cancer
June 26, 2023
Chicago, Illinois (Embargoed until 3:05 p.m. CDT, Monday, June 26, 2023)—A new therapeutic target has been discovered for metastatic bladder cancer, opening up the door for more effective detection and treatment of this deadly disease. The cell surface tumor antigen CUB domain containing protein 1 (CDCP1) was found to be present in all bladder cancer subtypes, most notably in an aggressive subtype that cannot be treated effectively with current therapies. This research was presented at the 2023 Society of Nuclear Medicine and Molecular Imaging Annual Meeting.
Bladder cancer is the second most common malignancy of the genitourinary tract, leading to more than 17,000 deaths in the United States each year. Despite recent FDA approvals of bladder cancer therapies, metastatic bladder cancer remains incurable, and new treatments strategies are needed.
“We know that bladder cancer is molecularly heterogeneous and uniformly fatal,” said Shalini Chopra, PhD, postdoctoral researcher at University of California, San Francisco, in San Francisco, California. “In this research we investigated the cell surface protein CDCP1 to see whether it is a viable target for bladder cancer radiopharmaceutical therapy using radiolabeled anti-CDCP1 antibodies.”
In the study, CDCP1 expression was evaluated in four bladder cancer datasets containing more than 1,000 biopsies. Immunohistochemistry was used 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 89Zr-4A06, a monoclonal antibody that targets CDCP1. Mice were then treated with 177Lu-4A06 to evaluate antitumor effects.
CDCP1 was expressed in 53 percent of primary bladder cancer biopsies, with the highest expression in the aggressive basal/squamous subtype. 89Zr-4A06 detected five human bladder cancer xenografts, and 177Lu-4A06 inhibited the growth of the bladder cancer xenografts as well.
“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,” noted 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.”
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| Figure 1. 89Zr-4A06 PET detects molecularly diverse human bladder cancer xenografts with varying levels of CDCP1 expression. Representative coronal and transverse PET/CT images acquired 72 hours post injection of 89Zr-4A06. The position of the tumor is indicated with blue arrow. |
Abstract 1409. “Theranostic targeting of CUB domain containing protein 1 (CDCP1) in multiple subtypes of bladder cancer.” Shalini Chopra, Sasank Sakhamuri, Jie Zhou, Jonathon Chou, James A. Wells, and Michael Evans, University of California, San Francisco, San Francisco, California.
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All 2023 SNMMI Annual Meeting abstracts can be found online.
About the Society of Nuclear Medicine and Molecular Imaging
The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and medical organization dedicated to advancing nuclear medicine and molecular imaging—vital elements of precision medicine that allow diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes.
SNMMI’s members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit www.snmmi.org.