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Cancers
Special Issues
Current Management of Castration-Resistant Prostate Cancer (CRPC)
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Current Management of Castration-Resistant Prostate Cancer (CRPC)

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 17939

Special Issue Editors

Prof. Dr. Martin Bögemann

E-Mail Website
Guest Editor
Universitätsklinikum Münster, Munster, Germany
Interests: genitourinary cancers; serum biomarkers; prognostic and predictive biomarkers; castration-resistant prostate cancer; anti-hormonal therapy; immunotherapy; clinical trials; liquid biopsy; drug development
Prof. Dr. Tilman Todenhöfer

E-Mail Website
Guest Editor
Studienpraxis Urologie, Nürtingen, Germany
Interests: genitourinary cancers; immunotherapy; clinical trials; targeted therapy; circulating biomarkers; urinary biomarkers

Special Issue Information

Dear Colleagues,

In recent years, the treatment of castration-resistant prostate cancer has witnessed dramatic advances. Currently, the inhibition of androgen receptor signaling, chemotherapy, and radioligand therapies in various sequences are the mainstay of therapy. However, sooner or later, primary or secondary resistance against any given therapy inevitably occurs. Reasons for this include sustained proliferative androgen receptor signaling, activating point mutations of the androgen receptor, alternative splicing of the androgen receptor, cell cycle activation, evading apoptosis, inducing angiogenesis, activating invasion and metastasis, defective DNA-repair machinery, evasion of immune control, and many more. All of these occur in the context of chronic inflammation and genomic instability. Castration-resistant prostate cancer is still uncurable, and accounts for nearly all prostate cancer-related deaths. Understanding the genetic and biological mechanisms leading to therapy resistance and sustaining progression is crucial to achieving further advances in the sequencing of available drugs and management of castration-resistant prostate cancer in general. Any experimental and clinical work potentially relevant to this Special Issue will be carefully considered for inclusion.

Prof. Dr. Martin Bögemann
Prof. Dr. Tilman Todenhöfer
Guest Editors

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

  • therapy sequencing
  • outcome
  • response
  • predictive biomarkers
  • prognostic biomarkers
  • treatment resistance
  • androgen receptor

Published Papers (6 papers)

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Research

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13 pages, 2424 KiB  
Article
Cross-Resistance between Platinum-Based Chemotherapy and PARP Inhibitors in Castration-Resistant Prostate Cancer
by Peter H. J. Slootbeek, Iris S. H. Kloots, Inge M. van Oort, Leonie I. Kroeze, Jack A. Schalken, Haiko J. Bloemendal and Niven Mehra
Cancers 2023, 15(10), 2814; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15102814 - 18 May 2023
Cited by 5 | Viewed by 1592
Abstract
Patients with metastatic castration-resistant prostate cancer (mCRPC) harbouring homologous recombination repair-related gene aberrations (HRRm) can derive meaningful benefits from both platinum-based chemotherapy (PlCh) and PARP inhibitors (PARPi). Cross-resistance between these agents is well-recognised in other tumour types but data on prostate cancer is [...] Read more.
Patients with metastatic castration-resistant prostate cancer (mCRPC) harbouring homologous recombination repair-related gene aberrations (HRRm) can derive meaningful benefits from both platinum-based chemotherapy (PlCh) and PARP inhibitors (PARPi). Cross-resistance between these agents is well-recognised in other tumour types but data on prostate cancer is lacking. In this retrospective pre-planned study, we assessed 28 HRRm mCRPC patients who received PlCh and PARPi. Progression-free survival (PFS) on initial therapy was longer than on subsequent therapy (median 5.3 vs. 3.4 months, p = 0.016). The median PFS of PlCh was influenced by the order of agents, with 3.6 months shorter PFS after PARPi than when administered first. The median PFS of PARPi was less influenced, with 0.9 months shorter PFS after PlCh than before. In the PARPi-first subgroup, six out of 16 evaluable patients (37.5%) had a >50% PSA decline to PlCh, and two of eight (25.0%) had a radiographic response to PlCh. In the PlCh-first subgroup, 6/10 (60.0%) had a >50% PSA decline, and 5/9 (55.6%) had a radiographic response to PARPi. These data show >40% of the cohort is sensitive to a subsequent HRR-targeting agent. PlCh appears to induce less cross-resistance than PARPi. Additional data on resistance mechanisms will be crucial in defining an optimal treatment sequence in HRRm mCRPC patients. Full article
(This article belongs to the Special Issue Current Management of Castration-Resistant Prostate Cancer (CRPC))
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Review

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19 pages, 1150 KiB  
Review
PARP Inhibitors in Advanced Prostate Cancer in Tumors with DNA Damage Signatures
by Ciara S. McNevin, Karen Cadoo, Anne-Marie Baird, Stephen P. Finn and Ray McDermott
Cancers 2022, 14(19), 4751; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194751 - 29 Sep 2022
Cited by 3 | Viewed by 2189
Abstract
Since 2010, significant progress has been made in the treatment of metastatic castrate resistant prostate cancer (mCRPC). While these advancements have improved survival, mCRPC remains a lethal disease, with a precision medicine framework that is lagging behind compared to other cancers. Poly (ADP-ribose) [...] Read more.
Since 2010, significant progress has been made in the treatment of metastatic castrate resistant prostate cancer (mCRPC). While these advancements have improved survival, mCRPC remains a lethal disease, with a precision medicine framework that is lagging behind compared to other cancers. Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) studies in prostate cancer (PCa) have focused primarily on the homologous recombination repair (HRR) genes, specifically BRCA1 and BRCA2. While homologous recombination deficiency (HRD) can be prompted by germline or somatic BRCA1/2 genetic mutations, it can also exist in tumors with intact BRCA1/BRCA2 genes. While the sensitivity of PARPi in tumors with non-BRCA DNA damage signatures is not as well established, it has been suggested that genomic alterations in DNA damage repair (DDR) genes other than BRCA may confer synthetic lethality with PARPI in mCRPC. The aim of this review is to summarize the literature on PARPi and their activity treating BRCA and non BRCA tumors with DNA damage signatures. Full article
(This article belongs to the Special Issue Current Management of Castration-Resistant Prostate Cancer (CRPC))
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17 pages, 1124 KiB  
Review
Advances in the Current Understanding of the Mechanisms Governing the Acquisition of Castration-Resistant Prostate Cancer
by Yifeng Mao, Gaowei Yang, Yingbang Li, Guowu Liang, Wangwang Xu and Mingqiu Hu
Cancers 2022, 14(15), 3744; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14153744 - 31 Jul 2022
Cited by 9 | Viewed by 2684
Abstract
Despite aggressive treatment and androgen-deprivation therapy, most prostate cancer patients ultimately develop castration-resistant prostate cancer (CRPC), which is associated with high mortality rates. However, the mechanisms governing the development of CRPC are poorly understood, and androgen receptor (AR) signaling has been shown to [...] Read more.
Despite aggressive treatment and androgen-deprivation therapy, most prostate cancer patients ultimately develop castration-resistant prostate cancer (CRPC), which is associated with high mortality rates. However, the mechanisms governing the development of CRPC are poorly understood, and androgen receptor (AR) signaling has been shown to be important in CRPC through AR gene mutations, gene overexpression, co-regulatory factors, AR shear variants, and androgen resynthesis. A growing number of non-AR pathways have also been shown to influence the CRPC progression, including the Wnt and Hh pathways. Moreover, non-coding RNAs have been identified as important regulators of the CRPC pathogenesis. The present review provides an overview of the relevant literature pertaining to the mechanisms governing the molecular acquisition of castration resistance in prostate cancer, providing a foundation for future, targeted therapeutic efforts. Full article
(This article belongs to the Special Issue Current Management of Castration-Resistant Prostate Cancer (CRPC))
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14 pages, 286 KiB  
Review
Molecular Mechanisms Related with Oligometastatic Prostate Cancer—Is It Just a Matter of Numbers?
by Cristian Surcel, Alexander Kretschmer, Cristian Mirvald, Ioanel Sinescu, Isabel Heidegger and Igor Tsaur
Cancers 2022, 14(3), 766; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030766 - 01 Feb 2022
Cited by 2 | Viewed by 1766
Abstract
During the last decade, the body of knowledge regarding the oligometastatic state has increased exponentially. Several molecular frameworks have been established, aiding our understanding of metastatic spread caused by genetically unstable cells that adapt to a tissue environment which is distant from the [...] Read more.
During the last decade, the body of knowledge regarding the oligometastatic state has increased exponentially. Several molecular frameworks have been established, aiding our understanding of metastatic spread caused by genetically unstable cells that adapt to a tissue environment which is distant from the primary tumor. In the current narrative review, we provide an overview of the current treatment landscape of oligometastatic cancer, focusing on the current biomarkers used in the identification of true oligometastatic disease and highlighting the impact of molecular imaging on stage shift in different scenarios. Finally, we address current and future directions regarding the use of genetic and epigenetic targeting treatments in oligometastatic prostate cancer. Full article
(This article belongs to the Special Issue Current Management of Castration-Resistant Prostate Cancer (CRPC))
17 pages, 687 KiB  
Review
Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation
by Kim van der Zande, Wim J. G. Oyen, Wilbert Zwart and Andries M. Bergman
Cancers 2021, 13(17), 4346; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13174346 - 27 Aug 2021
Cited by 14 | Viewed by 4034
Abstract
Radium-223 dichloride ([223Ra]RaCl2; Ra-223) is a targeted alpha-emitting radiopharmaceutical which results in an overall survival and health related quality of life (HRQoL) benefit in symptomatic patients with metastatic castration resistant prostate cancer (mCRPC) and predominantly bone metastasis. Although effective, [...] Read more.
Radium-223 dichloride ([223Ra]RaCl2; Ra-223) is a targeted alpha-emitting radiopharmaceutical which results in an overall survival and health related quality of life (HRQoL) benefit in symptomatic patients with metastatic castration resistant prostate cancer (mCRPC) and predominantly bone metastasis. Although effective, options to select patients who will derive treatment benefit and to monitor and predict treatment outcomes are limited. PSA response and radiographic evaluation are commonly used in mCRPC treatment assessment but are not informative in Ra-223 treated patients. Consequently, there is a clear need for predictive and prognostic tools. In this review, we discuss the physiology of bone metastases and the mechanism of action and efficacy of Ra-223 treatment, as well as offering an outline of current innovative prognostic and predictive biomarkers. Full article
(This article belongs to the Special Issue Current Management of Castration-Resistant Prostate Cancer (CRPC))
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17 pages, 1011 KiB  
Review
Bispecific Antibodies in Prostate Cancer Therapy: Current Status and Perspectives
by Jonas S. Heitmann, Martin Pfluegler, Gundram Jung and Helmut R. Salih
Cancers 2021, 13(3), 549; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13030549 - 01 Feb 2021
Cited by 12 | Viewed by 4547
Abstract
Prostate carcinoma (PC) is the second most common cancer in men. When the disease becomes unresponsive to androgen deprivation therapy, the remaining treatment options are of limited benefit. Despite intense efforts, none of the T cell-based immunotherapeutic strategies that meanwhile have become a [...] Read more.
Prostate carcinoma (PC) is the second most common cancer in men. When the disease becomes unresponsive to androgen deprivation therapy, the remaining treatment options are of limited benefit. Despite intense efforts, none of the T cell-based immunotherapeutic strategies that meanwhile have become a cornerstone for treatment of other malignancies is established in PC. This refers to immune checkpoint inhibition (CI), which generally reinforces T cell immunity as well as chimeric antigen receptor T (CAR-T) cells and bispecific antibodies (bsAbs) that stimulate the T cell receptor/CD3-complex and mobilize T cells in a targeted manner. In general, compared to CAR-T cells, bsAb would have the advantage of being an “off the shelf” reagent associated with less preparative effort, but at present, despite enormous efforts, neither CAR-T cells nor bsAbs are successful in solid tumors. Here, we focus on the various bispecific constructs that are presently in development for treatment of PC, and discuss underlying concepts and the state of clinical evaluation as well as future perspectives. Full article
(This article belongs to the Special Issue Current Management of Castration-Resistant Prostate Cancer (CRPC))
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