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Thomas Flaig, MD


Targeting CDCP1 Cell-Surface Protein Via Radiotherapy in Metastatic Bladder Cancer

By: Kayci Reyer
Posted: Thursday, March 16, 2023

According to research presented in Clinical Cancer Research, patients with metastatic bladder cancer that expresses CUB domain–containing protein 1 (CDCP1)—a cell-surface protein—may benefit from targeted treatment with radiolabeled antibodies. The findings indicate that CDCP1 may be expressed in disease subtypes that include TROP2 and/or NECTIN4-null tumors.

“We are optimistic that our data, combined with these prior clinical experiences, will provide a compelling rationale to advance [targeted radiotherapies] into clinical trials for patients with both localized and metastatic disease,” concluded corresponding authors Michael J. Evans, PhD, and Jonathan Chou, MD, PhD (both of the University of California, San Francisco), and colleagues.

The study included four bladder cancer data sets comprising 1,047 biopsies. Immunohistochemistry was employed to evaluate tissues from primary bladder cancer biopsies and to detect the presence of CDCP1. In murine models, Zr-labeled 4A06, a monoclonal antibody targeting the CDCP1 ectodomain, was used to radiographically visualize tumor presence. Mice harboring UMUC3 or HT1376 xenografts were administered Lu-4A06 to determine antitumor activity.

Overall, CDCP1 expression was observed in 53% of biopsies and was highest among patients with basal or squamous subtypes. According to the investigators, surface expression of CDCP1 varied, with receptors ranging between 105 and 106 per cell. No association was observed between CDCP1 expression and tumor stage, metastatic site, or presence of NECTIN4 and TROP2 in either mRNA or protein. Lu-4A06 successfully inhibited tumor growth in both the UMUC3 and HT1376 xenograft models. Expression of CDCP1 was noted to dependent on RAS signaling.

Disclosure: For full disclosures of the study authors, visit

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