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Open Access 20-10-2023 | Prostate Cancer

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer—Combination Strategies

Authors: Daria Arbuznikova, Matthias Eder, Anca-Ligia Grosu, Philipp T. Meyer, Christian Gratzke, Constantinos Zamboglou, Ann-Christin Eder

Published in: Current Oncology Reports | Issue 11/2023

Abstract

Purpose of Review

[¹⁷⁷Lu]Lu-PSMA-617 is a radiopharmaceutical that emits beta-minus radiation and targets prostate-specific membrane antigen (PSMA)-positive prostate cancer. Despite its clinical success, there are still patients not showing sufficient response rates. This review compiles latest studies aiming at therapy improvement in [¹⁷⁷Lu]Lu-PSMA-617-naïve and -resistant patients by alternative or combination treatments.

Recent Findings

A variety of agents to combine with [¹⁷⁷Lu]Lu-PSMA-617 are currently under investigation including alpha radiation-emitting pharmaceuticals, radiosensitizers, taxane chemotherapeutics, androgen receptor pathway inhibitors, immune checkpoint inhibitors, and external beam radiation. Actinium-225 (²²⁵Ac)-labeled PSMA-targeting inhibitors are the most studied pharmaceuticals for combination therapy or as an alternative for treatment after progression under [¹⁷⁷Lu]Lu-PSMA-617 therapy.

Summary

Alpha emitters seem to have a potential of achieving a response to PSMA-targeting radionuclide therapy in both initial non-responders or responders to [¹⁷⁷Lu]Lu-PSMA-617 later developing treatment resistance. Emerging evidence for immunostimulatory effects of radiopharmaceuticals and first prospective studies support the combination of [¹⁷⁷Lu]Lu-PSMA-617 and immune checkpoint inhibition for late-stage prostate cancer.

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Title: Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer—Combination Strategies
Authors: Daria Arbuznikova
Matthias Eder
Anca-Ligia Grosu
Philipp T. Meyer
Christian Gratzke
Constantinos Zamboglou
Ann-Christin Eder
Publication date: 20-10-2023
Publisher: Springer US
Keywords: Prostate Cancer
Prostate Cancer
Radionuclide Therapy
Enzalutamide
Androgens
Published in: Current Oncology Reports / Issue 11/2023
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI: https://doi.org/10.1007/s11912-023-01458-6

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