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Receptor CDCP1 Is a Potential Target for Personalized Imaging and Treatment of Poor Outcome HER2+, Triple-Negative, and Metastatic ER+/HER2- Breast Cancers

  • 0Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Australia.
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research +

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January 27, 2025

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January 27, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Receptor CUB domain-containing protein 1 (CDCP1) shows promise as a target for breast cancer detection and treatment. CDCP1-targeted therapies, including antibody-drug conjugates, demonstrate significant efficacy in preclinical models.

Area Of Science

  • Oncology
  • Molecular Imaging
  • Drug Development

Background

  • Receptor CUB domain-containing protein 1 (CDCP1) is a cell surface protein implicated in cancer progression.
  • Understanding CDCP1 expression patterns is crucial for developing targeted breast cancer therapies.

Purpose Of The Study

  • To evaluate CDCP1 as a target for breast cancer detection and treatment.
  • To assess the efficacy of a CDCP1-targeting antibody-drug conjugate (ADC) in preclinical models.

Main Methods

  • Immunohistochemical analysis of CDCP1 expression in 423 breast cancer patient tumors.
  • In vitro cytotoxicity assays of CDCP1-targeting ADC (ch10D7-MMAE) alone and in combination with trastuzumab emtansine (T-DM1).
  • PET-CT imaging using zirconium-89-labeled ch10D7 for xenograft detection.
  • In vivo efficacy studies in mouse models of triple-negative breast cancer (TNBC) and HER2+ breast cancer.

Main Results

  • CDCP1 is expressed on a high percentage of triple-negative breast cancer (TNBC) and HER2+ tumors, with increasing expression in metastatic ER+/HER2- breast cancer.
  • PET-CT imaging effectively detected CDCP1-expressing primary and metastatic TNBC xenografts in mice.
  • The CDCP1-targeting ADC ch10D7-MMAE demonstrated potent in vitro and in vivo anti-tumor activity against CDCP1-expressing xenografts, outperforming chemotherapy.
  • Combination therapy with ch10D7-MMAE and T-DM1 exhibited the most significant anti-tumor efficacy in CDCP1+/HER2+ xenografts, prolonging survival.

Conclusions

  • CDCP1 is a viable target for molecular imaging and targeted therapy in aggressive breast cancers.
  • CDCP1-directed imaging can identify patients eligible for CDCP1-targeted treatments.
  • The combination of CDCP1-targeted ADC and HER2-targeted ADC holds significant therapeutic potential for breast cancer treatment.