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Cancers
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Precision Medicine in Prostate Cancer
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Precision Medicine in Prostate Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 25120

Special Issue Editors

Dr. Orazio Caffo

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Guest Editor
Department of Medical Oncology, Santa Chiara Hospital, 38112 Trento, Italy
Interests: prostate cancer; bladder cancer; renal cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Carlo Messina

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Guest Editor
Department of Medical Oncology, Santa Chiara Hospital, 38112 Trento, Italy
Interests: prostate cancer; meta-analyses

Special Issue Information

Dear Colleagues,

In the last few decades, the treatment of several kinds of tumors underwent a dramatic change of therapeutic strategies, moving from a traditional approach, where the tumors from a specific organ were treated in the same manner, to a revolutionary approach, known as “precision medicine.” It let the clinicians tailor their therapeutic strategies for each patient according to the specific features characterizing his/her disease. This innovative approach led to unprecedented improvements in disease control and survival, significantly changing the prognosis of several types of cancers. The greatest improvements by precision medicine were observed in those tumors where research was able to identify molecular mechanisms which cooperate to cancer cells development and growth and can represent therapeutic targets. In the case of prostate cancer the concept of precision medicine appears only recently and we are still waiting to fully exploit the potential benefit from this innovative approach.

The present issue of Cancers aims to summarize: 1) our actual knowledge about molecular mechanisms which sustain prostate cancer growth and can be potentially hit by specific therapeutic agents; 2) the potential fields for applying precision medicine in prostate cancer; 3) the completed or ongoing trials based on precision medicine in prostate cancer.

Dr. Orazio Caffo
Dr. Carlo Messina
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • prostate cancer
  • precision medicine
  • molecular target
  • ongoing trials
  • combination therapy

Published Papers (5 papers)

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Review

16 pages, 730 KiB  
Review
Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives
by Sara Elena Rebuzzi, Pasquale Rescigno, Fabio Catalano, Veronica Mollica, Ursula Maria Vogl, Laura Marandino, Francesco Massari, Ricardo Pereira Mestre, Elisa Zanardi, Alessio Signori, Sebastiano Buti, Matteo Bauckneht, Silke Gillessen, Giuseppe Luigi Banna and Giuseppe Fornarini
Cancers 2022, 14(5), 1245; https://doi.org/10.3390/cancers14051245 - 28 Feb 2022
Cited by 24 | Viewed by 5753
Abstract
In the last 10 years, many new therapeutic options have been approved in advanced prostate cancer (PCa) patients, granting a more prolonged survival in patients with metastatic disease, which, nevertheless, remains incurable. The emphasis on immune checkpoint inhibitors (ICIs) has led to many [...] Read more.
In the last 10 years, many new therapeutic options have been approved in advanced prostate cancer (PCa) patients, granting a more prolonged survival in patients with metastatic disease, which, nevertheless, remains incurable. The emphasis on immune checkpoint inhibitors (ICIs) has led to many trials in this setting, with disappointing results until now. Therefore, we discuss the immunobiology of PCa, presenting ongoing trials and the available clinical data, to understand if immunotherapy could represent a valid option in this disease, and which subset of patients may be more likely to benefit. Current evidence suggests that the tumor microenvironment needs a qualitative rather than quantitative evaluation, along with the genomic determinants of prostate tumor cells. The prognostic or predictive value of immunotherapy biomarkers, such as PD-L1, TMB, or dMMR/MSI-high, needs further evaluation in PCa. Monotherapy with immune checkpoint inhibitors (ICIs) has been modestly effective. In contrast, combined strategies with other standard treatments (hormonal agents, chemotherapy, PARP inhibitors, radium-223, and TKIs) have shown some results. Immunotherapy should be better investigated in biomarker-selected patients, particularly with specific pathway aberrations (e.g., AR-V7 variant, HRD, CDK12 inactivated tumors, MSI-high tumors). Lastly, we present new possible targets in PCa that could potentially modulate the tumor microenvironment and improve antitumor activity with ICIs. Full article
(This article belongs to the Special Issue Precision Medicine in Prostate Cancer)
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22 pages, 2314 KiB  
Review
Past, Current, and Future Strategies to Target ERG Fusion-Positive Prostate Cancer
by Francesca Lorenzin and Francesca Demichelis
Cancers 2022, 14(5), 1118; https://doi.org/10.3390/cancers14051118 - 22 Feb 2022
Cited by 11 | Viewed by 5477
Abstract
The ETS family member ERG is a transcription factor with physiological roles during development and in the vascular and hematopoietic systems. ERG oncogenic activity characterizes several malignancies, including Ewing’s sarcoma, leukemia and prostate cancer (PCa). In PCa, ERG rearrangements with androgen-regulated genes—mostly TMPRSS2 [...] Read more.
The ETS family member ERG is a transcription factor with physiological roles during development and in the vascular and hematopoietic systems. ERG oncogenic activity characterizes several malignancies, including Ewing’s sarcoma, leukemia and prostate cancer (PCa). In PCa, ERG rearrangements with androgen-regulated genes—mostly TMPRSS2—characterize a large subset of patients across disease progression and result in androgen receptor (AR)-mediated overexpression of ERG in the prostate cells. Importantly, PCa cells overexpressing ERG are dependent on ERG activity for survival, further highlighting its therapeutic potential. Here, we review the current understanding of the role of ERG and its partners in PCa. We discuss the strategies developed in recent years to inhibit ERG activity, the current therapeutic utility of ERG fusion detection in PCa patients, and the possible future approaches to target ERG fusion-positive tumors. Full article
(This article belongs to the Special Issue Precision Medicine in Prostate Cancer)
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Figure 1

23 pages, 1023 KiB  
Review
Molecular Characterization of Prostate Cancers in the Precision Medicine Era
by Emilio Francesco Giunta, Laura Annaratone, Enrico Bollito, Francesco Porpiglia, Matteo Cereda, Giuseppe Luigi Banna, Alessandra Mosca, Caterina Marchiò and Pasquale Rescigno
Cancers 2021, 13(19), 4771; https://doi.org/10.3390/cancers13194771 - 24 Sep 2021
Cited by 12 | Viewed by 3553
Abstract
Prostate cancer (PCa) therapy has been recently revolutionized by the approval of new therapeutic agents in the metastatic setting. However, the optimal therapeutic strategy in such patients should be individualized in the light of prognostic and predictive molecular factors, which have been recently [...] Read more.
Prostate cancer (PCa) therapy has been recently revolutionized by the approval of new therapeutic agents in the metastatic setting. However, the optimal therapeutic strategy in such patients should be individualized in the light of prognostic and predictive molecular factors, which have been recently studied: androgen receptor (AR) alterations, PTEN-PI3K-AKT pathway deregulation, homologous recombination deficiency (HRD), mismatch repair deficiency (MMRd), and tumor microenvironment (TME) modifications. In this review, we highlighted the clinical impact of prognostic and predictive molecular factors in PCa patients’ outcomes, identifying biologically distinct subtypes. We further analyzed the relevant methods to detect these factors, both on tissue, i.e., immunohistochemistry (IHC) and molecular tests, and blood, i.e., analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Moreover, we discussed the main pros and cons of such techniques, depicting their present and future roles in PCa management, throughout the precision medicine era. Full article
(This article belongs to the Special Issue Precision Medicine in Prostate Cancer)
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28 pages, 1233 KiB  
Review
Optimal Sequencing and Predictive Biomarkers in Patients with Advanced Prostate Cancer
by Carlo Cattrini, Rodrigo España, Alessia Mennitto, Melissa Bersanelli, Elena Castro, David Olmos, David Lorente and Alessandra Gennari
Cancers 2021, 13(18), 4522; https://doi.org/10.3390/cancers13184522 - 8 Sep 2021
Cited by 24 | Viewed by 5573
Abstract
The treatment landscape of advanced prostate cancer has completely changed during the last decades. Chemotherapy (docetaxel, cabazitaxel), androgen-receptor signaling inhibitors (ARSi) (abiraterone acetate, enzalutamide), and radium-223 have revolutionized the management of metastatic castration-resistant prostate cancer (mCRPC). Lutetium-177–PSMA-617 is also going to become another [...] Read more.
The treatment landscape of advanced prostate cancer has completely changed during the last decades. Chemotherapy (docetaxel, cabazitaxel), androgen-receptor signaling inhibitors (ARSi) (abiraterone acetate, enzalutamide), and radium-223 have revolutionized the management of metastatic castration-resistant prostate cancer (mCRPC). Lutetium-177–PSMA-617 is also going to become another treatment option for these patients. In addition, docetaxel, abiraterone acetate, apalutamide, enzalutamide, and radiotherapy to primary tumor have demonstrated the ability to significantly prolong the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Finally, apalutamide, enzalutamide, and darolutamide have recently provided impactful data in patients with nonmetastatic castration-resistant disease (nmCRPC). However, which is the best treatment sequence for patients with advanced prostate cancer? This comprehensive review aims at discussing the available literature data to identify the optimal sequencing approaches in patients with prostate cancer at different disease stages. Our work also highlights the potential impact of predictive biomarkers in treatment sequencing and exploring the role of specific agents (i.e., olaparib, rucaparib, talazoparib, niraparib, and ipatasertib) in biomarker-selected populations of patients with prostate cancer (i.e., those harboring alterations in DNA damage and response genes or PTEN). Full article
(This article belongs to the Special Issue Precision Medicine in Prostate Cancer)
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16 pages, 794 KiB  
Review
AR Splicing Variants and Resistance to AR Targeting Agents
by Mayuko Kanayama, Changxue Lu, Jun Luo and Emmanuel S. Antonarakis
Cancers 2021, 13(11), 2563; https://doi.org/10.3390/cancers13112563 - 23 May 2021
Cited by 27 | Viewed by 3892
Abstract
Over the past decade, advances in prostate cancer research have led to discovery and development of novel biomarkers and effective treatments. As treatment options diversify, it is critical to further develop and use optimal biomarkers for the purpose of maximizing treatment benefit and [...] Read more.
Over the past decade, advances in prostate cancer research have led to discovery and development of novel biomarkers and effective treatments. As treatment options diversify, it is critical to further develop and use optimal biomarkers for the purpose of maximizing treatment benefit and minimizing unwanted adverse effects. Because most treatments for prostate cancer target androgen receptor (AR) signaling, aberrations affecting this drug target are likely to emerge following the development of castration-resistant prostate cancer (CRPC), and it is conceivable that such aberrations may play a role in drug resistance. Among the many AR aberrations, we and others have been studying androgen receptor splice variants (AR-Vs), especially AR-V7, and have conducted preclinical and clinical studies to develop and validate the clinical utility of AR-V7 as a prognostic and potential predictive biomarker. In this review, we first describe mechanisms of AR-V generation, regulation and their functions from a molecular perspective. We then discuss AR-Vs from a clinical perspective, focusing on the significance of AR-Vs detected in different types of human specimens and AR-Vs as potential therapeutic targets. Full article
(This article belongs to the Special Issue Precision Medicine in Prostate Cancer)
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