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Immune-checkpoint inhibitors and metastatic prostate cancer therapy: Learning by making mistakes

Mélanie Claps1, Alessia Mennitto1, Valentina Guadalupi1

  • 1Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.

Cancer Treatment Reviews
|June 24, 2020
PubMed

Insights

Prostate cancer shows limited response to immune-checkpoint inhibitors due to its tumor microenvironment. Future research should explore novel strategies to enhance immunotherapy effectiveness in advanced prostate cancer.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Research

Background:

  • Metastatic prostate cancer, particularly castration-resistant prostate cancer (CRPC), has a poor prognosis despite therapeutic advances.
  • Immune-checkpoint inhibitors (ICIs) have shown success in other solid tumors but yield limited benefits in advanced prostate cancer.
  • Current research focuses on understanding resistance mechanisms to improve ICI efficacy.

Purpose of the Study:

  • To review the efficacy of immune-checkpoint inhibitors in treating advanced prostate cancer.
  • To analyze the mechanisms underlying resistance and sensitivity to ICIs in prostate cancer.
  • To identify potential future research directions for optimizing prostate cancer immunotherapy.

Main Methods:

  • Review of preliminary phase I and II clinical trials evaluating ICIs (CTLA-4, PD-1) in advanced prostate cancer.
  • Analysis of studies investigating combinations of ICIs with vaccines, radiotherapy, or hormonal therapy.
  • Examination of factors contributing to prostate cancer's poor response to immunotherapy, including tumor mutational burden and immune-suppressive microenvironment.

Main Results:

  • Limited biochemical and radiological responses observed with current ICI monotherapy or combination strategies.
  • Prostate cancer's low tumor mutational burden and immune-suppressive tumor microenvironment are key challenges.
  • Preliminary data from early-phase trials show modest efficacy.

Conclusions:

  • Prostate cancer exhibits poor response to current immune-checkpoint inhibitor therapies.
  • Understanding the tumor microenvironment and resistance mechanisms is crucial for developing effective treatments.
  • Further research is needed to identify novel strategies and biomarkers to enhance ICI efficacy in advanced prostate cancer.
Keywords:
Combination therapyImmune-checkpoints inhibitorsImmune-suppressive phenotypeProstate cancerTumor mutational burden

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