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Antibody–Drug Conjugates in Uro-Oncology

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Abstract

Currently available treatment options for patients with refractory metastatic prostate, bladder, or kidney cancers are limited with the prognosis remaining poor. Advances in the pathobiology of tumors has led to the discovery of cancer antigens that may be used as the target for cancer treatment. Antibody–drug conjugates (ADCs) are a relatively new concept in cancer treatment that broaden therapeutic landscape. ADCs are examples of a ‘drug delivery into the tumor’ system composed of an antigen-directed antibody linked to a cytotoxic drug that may release cytotoxic components after binding to the antigen located on the surface of tumor cells. The clinical properties of drugs are influenced by every component of ADCs. Regarding uro-oncology, enfortumab vedotin (EV) and sacituzumab govitecan (SG) are currently registered for patients with locally advanced or metastatic urothelial cancer following previous treatment with an immune checkpoint inhibitor (iCPI; programmed death receptor-1 [PD-1] or programmed death-ligand 1 [PD-L1]) inhibitor) and platinum-containing chemotherapy. The EV-301 trial showed that EV significantly prolonged the overall survival compared with classic chemotherapy. The TROPHY-U-01 trial conducted to evaluate SG demonstrated promising results as regards the objective response rate and duration of response. The safety and efficacy of ADCs in monotherapy and polytherapy (mainly with iCPIs) for different cancer stages and tumor types are assessed in numerous ongoing clinical trials. The aim of this review is to present new molecular biomarkers, specific mechanisms of action, and ongoing clinical trials of ADCs in genitourinary cancers. In the expert discussion, we assess the place of ADCs in uro-oncology and discuss their clinical value.

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Authors and Affiliations

  1. Department of Oncology, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland

    Dawid Sigorski

  2. Department of Oncology and Immuno-Oncology, Warmian-Masurian Cancer Center of the Ministry of the Interior and Administration Hospital, Olsztyn, Poland

    Dawid Sigorski

  3. Department of Clinical Oncology and Immuno-Oncology, Greater Poland Cancer Centre, Poznan, Poland

    Paweł Różanowski

  4. Department of Pathology and Neuropathology, Medical University of Gdańsk, Gdańsk, Poland

    Ewa Iżycka-Świeszewska

  5. Department of Pathomorphology, Copernicus Hospital, Gdańsk, Poland

    Ewa Iżycka-Świeszewska

  6. Department of Drug Biotechnology and Bioinformatics, National Medicines Institute, Warsaw, Poland

    Katarzyna Wiktorska

  7. OncoBoost Ltd, Warsaw, Poland

    Katarzyna Wiktorska

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  1. Dawid Sigorski
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  2. Paweł Różanowski
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Correspondence to Dawid Sigorski.

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Dawid Sigorski, Paweł Różanowski, Ewa Iżycka-Świeszewska, and Katarzyna Wiktorska declare they have no conflicts of interest that might be relevant to the contents of this manuscript.

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All authors contributed to the study concept and design. The idea for the article was conceived by PR and DS, and the literature search and data analysis was undertaken by DS, PR, KW, and EI-Ś. Drafting of the manuscript was performed by DS, and critical revision of the manuscript was performed by PR, EI-Ś, and KW.

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Sigorski, D., Różanowski, P., Iżycka-Świeszewska, E. et al. Antibody–Drug Conjugates in Uro-Oncology. Targ Oncol 17, 203–221 (2022). https://doi.org/10.1007/s11523-022-00872-3

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