Is There a Role for Immunotherapy in Prostate Cancer?

In the last decade, immunotherapy has revolutionized the treatment landscape of several hematological and solid malignancies, reporting unprecedented response rates. Unfortunately, this is not the case for metastatic castration-resistant prostate cancer (mCRPC), as several phase I and II trials asse...

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Veröffentlicht in:Cells (Basel, Switzerland) Jg. 9; H. 9; S. 2051
Hauptverfasser: Rizzo, Alessandro, Mollica, Veronica, Cimadamore, Alessia, Santoni, Matteo, Scarpelli, Marina, Giunchi, Francesca, Cheng, Liang, Lopez-Beltran, Antonio, Fiorentino, Michelangelo, Montironi, Rodolfo, Massari, Francesco
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Veröffentlicht: Switzerland MDPI AG 08.09.2020
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Abstract In the last decade, immunotherapy has revolutionized the treatment landscape of several hematological and solid malignancies, reporting unprecedented response rates. Unfortunately, this is not the case for metastatic castration-resistant prostate cancer (mCRPC), as several phase I and II trials assessing programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors have shown limited benefits. Moreover, despite sipuleucel-T representing the only cancer vaccine approved by the Food and Drug Administration (FDA) for mCRPC following the results of the IMPACT trial, the use of this agent is relatively limited in everyday clinical practice. The identification of specific histological and molecular biomarkers that could predict response to immunotherapy represents one of the current challenges, with an aim to detect subgroups of mCRPC patients who may benefit from immune checkpoint monoclonal antibodies as monotherapy or in combination with other anticancer agents. Several unanswered questions remain, including the following: is there—or will there ever be—a role for immunotherapy in prostate cancer? In this review, we aim at underlining the failures and promises of immunotherapy in prostate cancer, summarizing the current state of art regarding cancer vaccines and immune checkpoint monoclonal antibodies, and discussing future research directions in this immunologically “cold” malignancy.
AbstractList In the last decade, immunotherapy has revolutionized the treatment landscape of several hematological and solid malignancies, reporting unprecedented response rates. Unfortunately, this is not the case for metastatic castration-resistant prostate cancer (mCRPC), as several phase I and II trials assessing programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors have shown limited benefits. Moreover, despite sipuleucel-T representing the only cancer vaccine approved by the Food and Drug Administration (FDA) for mCRPC following the results of the IMPACT trial, the use of this agent is relatively limited in everyday clinical practice. The identification of specific histological and molecular biomarkers that could predict response to immunotherapy represents one of the current challenges, with an aim to detect subgroups of mCRPC patients who may benefit from immune checkpoint monoclonal antibodies as monotherapy or in combination with other anticancer agents. Several unanswered questions remain, including the following: is there—or will there ever be—a role for immunotherapy in prostate cancer? In this review, we aim at underlining the failures and promises of immunotherapy in prostate cancer, summarizing the current state of art regarding cancer vaccines and immune checkpoint monoclonal antibodies, and discussing future research directions in this immunologically “cold” malignancy.
In the last decade, immunotherapy has revolutionized the treatment landscape of several hematological and solid malignancies, reporting unprecedented response rates. Unfortunately, this is not the case for metastatic castration-resistant prostate cancer (mCRPC), as several phase I and II trials assessing programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors have shown limited benefits. Moreover, despite sipuleucel-T representing the only cancer vaccine approved by the Food and Drug Administration (FDA) for mCRPC following the results of the IMPACT trial, the use of this agent is relatively limited in everyday clinical practice. The identification of specific histological and molecular biomarkers that could predict response to immunotherapy represents one of the current challenges, with an aim to detect subgroups of mCRPC patients who may benefit from immune checkpoint monoclonal antibodies as monotherapy or in combination with other anticancer agents. Several unanswered questions remain, including the following: is there-or will there ever be-a role for immunotherapy in prostate cancer? In this review, we aim at underlining the failures and promises of immunotherapy in prostate cancer, summarizing the current state of art regarding cancer vaccines and immune checkpoint monoclonal antibodies, and discussing future research directions in this immunologically "cold" malignancy.In the last decade, immunotherapy has revolutionized the treatment landscape of several hematological and solid malignancies, reporting unprecedented response rates. Unfortunately, this is not the case for metastatic castration-resistant prostate cancer (mCRPC), as several phase I and II trials assessing programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors have shown limited benefits. Moreover, despite sipuleucel-T representing the only cancer vaccine approved by the Food and Drug Administration (FDA) for mCRPC following the results of the IMPACT trial, the use of this agent is relatively limited in everyday clinical practice. The identification of specific histological and molecular biomarkers that could predict response to immunotherapy represents one of the current challenges, with an aim to detect subgroups of mCRPC patients who may benefit from immune checkpoint monoclonal antibodies as monotherapy or in combination with other anticancer agents. Several unanswered questions remain, including the following: is there-or will there ever be-a role for immunotherapy in prostate cancer? In this review, we aim at underlining the failures and promises of immunotherapy in prostate cancer, summarizing the current state of art regarding cancer vaccines and immune checkpoint monoclonal antibodies, and discussing future research directions in this immunologically "cold" malignancy.
Audience Academic
Author Scarpelli, Marina
Giunchi, Francesca
Montironi, Rodolfo
Cimadamore, Alessia
Santoni, Matteo
Rizzo, Alessandro
Lopez-Beltran, Antonio
Cheng, Liang
Massari, Francesco
Mollica, Veronica
Fiorentino, Michelangelo
AuthorAffiliation 2 Section of Pathological Anatomy, School of Medicine, Polytechnic University of the Marche Region, United Hospitals, 60126 Ancona, Italy; alessiacimadamore@gmail.com (A.C.); m.scarpelli@univpm.it (M.S.); r.montironi@staff.univpm.it (R.M.)
6 Department of Surgery, Cordoba University Medical School, 14071 Cordoba, Spain; em1lobea@gmail.com
4 Department of Pathology, Ospedale Maggiore and University of Bologna, 40138 Bologna, Italy; frachikka@virgilio.it (F.G.); michelangelo.fiorentino@unibo.it (M.F.)
5 Laboratory Medicine and Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
3 Oncology Unit, Macerata Hospital, 62012 Macerata, Italy; mattymo@alice.it
1 Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, via Albertoni, 40138 Bologna, Italy; rizzo.alessandro179@gmail.com (A.R.); veronica.mollica7@gmail.com (V.M.)
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– name: 4 Department of Pathology, Ospedale Maggiore and University of Bologna, 40138 Bologna, Italy; frachikka@virgilio.it (F.G.); michelangelo.fiorentino@unibo.it (M.F.)
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/32911806$$D View this record in MEDLINE/PubMed
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Issue 9
Keywords predictive biomarkers
prostate cancer
vaccines
immunotherapy
combination therapy
CTLA-4
immune checkpoint inhibitors
pd-1
Language English
License Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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These authors contributed equally to this work as last authors.
These authors contributed equally to this work as first authors.
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Snippet In the last decade, immunotherapy has revolutionized the treatment landscape of several hematological and solid malignancies, reporting unprecedented response...
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SubjectTerms Antibodies
Antitumor agents
Biomarkers
Cancer vaccines
Care and treatment
Castration
Clinical trials
CTLA-4
CTLA-4 protein
Cytotoxicity
FDA approval
Humans
Immune checkpoint
Immunotherapy
Immunotherapy - methods
Kidney cancer
Lymphocytes T
Male
Malignancy
Melanoma
Metastases
Metastasis
Methods
Monoclonal antibodies
Mutation
pd-1
PD-1 protein
predictive biomarkers
Prostate cancer
Prostatic Neoplasms - immunology
Prostatic Neoplasms - therapy
Radiation therapy
Review
Skin cancer
Tumors
Vaccines
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