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5 pages, 516 KiB

Open AccessEditorial

Update on Prostate Cancer Diagnosis, Prognosis, and Prediction to Response to Therapy

by Rodolfo Montironi, Alessia Cimadamore, Antonio Lopez-Beltran, Liang Cheng and Marina Scarpelli

Cells 2021, 10(1), 20; https://doi.org/10.3390/cells10010020 - 24 Dec 2020

Cited by 5 | Viewed by 1930

Abstract

The wide range of novelties reported in this Special Issue of the journal Cells on prostate cancer (PCa) diagnosis, prognosis, and prediction to response to therapy, has led us to a series of considerations related to a better understanding of the current and [...] Read more.

The wide range of novelties reported in this Special Issue of the journal Cells on prostate cancer (PCa) diagnosis, prognosis, and prediction to response to therapy, has led us to a series of considerations related to a better understanding of the current and future role of effective molecular biomarkers in individual patients with PCa [...] Full article

(This article belongs to the Special Issue Update on Prostate Cancer Diagnosis, Prognosis and Prediction to Response to Therapy)

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Review

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14 pages, 671 KiB

Open AccessReview

Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications

by Gaetano Aurilio, Alessia Cimadamore, Roberta Mazzucchelli, Antonio Lopez-Beltran, Elena Verri, Marina Scarpelli, Francesco Massari, Liang Cheng, Matteo Santoni and Rodolfo Montironi

Cells 2020, 9(12), 2653; https://doi.org/10.3390/cells9122653 - 10 Dec 2020

Cited by 89 | Viewed by 8557

Abstract

Around 80–90% of prostate cancer (PCa) cases are dependent on androgens at initial diagnosis; hence, androgen ablation therapy directed toward a reduction in serum androgens and the inhibition of androgen receptor (AR) is generally the first therapy adopted. However, the patient’s response to [...] Read more.

Around 80–90% of prostate cancer (PCa) cases are dependent on androgens at initial diagnosis; hence, androgen ablation therapy directed toward a reduction in serum androgens and the inhibition of androgen receptor (AR) is generally the first therapy adopted. However, the patient’s response to androgen ablation therapy is variable, and 20–30% of PCa cases become castration resistant (CRPCa). Several mechanisms can guide treatment resistance to anti-AR molecules. In this regard, AR-dependent and -independent resistance mechanisms can be distinguished within the AR pathway. In this article, we investigate the multitude of AR signaling aspects, encompassing the biological structure of AR, current AR-targeted therapies, mechanisms driving resistance to AR, and AR crosstalk with other pathways, in an attempt to provide a comprehensive review for the PCa research community. We also summarize the new anti-AR drugs approved in non-metastatic castration-resistant PCa, in the castration-sensitive setting, and combination therapies with other drugs. Full article

(This article belongs to the Special Issue Update on Prostate Cancer Diagnosis, Prognosis and Prediction to Response to Therapy)

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13 pages, 1147 KiB

Open AccessReview

Clinical Actionability of the Genomic Landscape of Metastatic Castration Resistant Prostate Cancer

by Wout Devlies, Markus Eckstein, Alessia Cimadamore, Gaëtan Devos, Lisa Moris, Thomas Van den Broeck, Rodolfo Montironi, Steven Joniau, Frank Claessens and Thomas Gevaert

Cells 2020, 9(11), 2494; https://doi.org/10.3390/cells9112494 - 17 Nov 2020

Cited by 12 | Viewed by 2706

Abstract

The development of targeted therapies increases treatment options for metastatic castration resistant prostate cancer (mCRPC) patients. There is a need for strong predictive and prognostic signatures to guide physicians in treating mCRPC patients. In this review we unravel the possible actionability in the [...] Read more.

The development of targeted therapies increases treatment options for metastatic castration resistant prostate cancer (mCRPC) patients. There is a need for strong predictive and prognostic signatures to guide physicians in treating mCRPC patients. In this review we unravel the possible actionability in the AR pathway, PI3K AKT signaling, and DNA repair pathways. Additionally, we make recommendations on biomarker trial design, and the clinical use of this new type of data. Full article

(This article belongs to the Special Issue Update on Prostate Cancer Diagnosis, Prognosis and Prediction to Response to Therapy)

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12 pages, 483 KiB

Open AccessReview

Incorporating Prognostic Biomarkers into Risk Assessment Models and TNM Staging for Prostate Cancer

by Ragheed Saoud, Nassib Abou Heidar, Alessia Cimadamore and Gladell P. Paner

Cells 2020, 9(9), 2116; https://doi.org/10.3390/cells9092116 - 17 Sep 2020

Cited by 13 | Viewed by 3415

Abstract

In current practice, prostate cancer staging alone is not sufficient to adequately assess the patient’s prognosis and plan the management strategies. Multiple clinicopathological parameters and risk tools for prostate cancer have been developed over the past decades to better characterize the disease and [...] Read more.

In current practice, prostate cancer staging alone is not sufficient to adequately assess the patient’s prognosis and plan the management strategies. Multiple clinicopathological parameters and risk tools for prostate cancer have been developed over the past decades to better characterize the disease and provide an enhanced assessment of prognosis. Herein, we review novel prognostic biomarkers and their integration into risk assessment models for prostate cancer focusing on their capability to help avoid unnecessary imaging studies, biopsies and diagnosis of low risk prostate cancers, to help in the decision-making process between active surveillance and treatment intervention, and to predict recurrence after radical prostatectomy. There is an imperative need of reliable biomarkers to stratify prostate cancer patients that may benefit from different management approaches. The integration of biomarkers panel with risk assessment models appears to improve prostate cancer diagnosis and management. However, integration of novel genomic biomarkers in future prognostic models requires further validation in their clinical efficacy, standardization, and cost-effectiveness in routine application. Full article

(This article belongs to the Special Issue Update on Prostate Cancer Diagnosis, Prognosis and Prediction to Response to Therapy)

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24 pages, 1409 KiB

Open AccessReview

Is There a Role for Immunotherapy in Prostate Cancer?

by Alessandro Rizzo, Veronica Mollica, Alessia Cimadamore, Matteo Santoni, Marina Scarpelli, Francesca Giunchi, Liang Cheng, Antonio Lopez-Beltran, Michelangelo Fiorentino, Rodolfo Montironi and Francesco Massari

Cells 2020, 9(9), 2051; https://doi.org/10.3390/cells9092051 - 08 Sep 2020

Cited by 66 | Viewed by 5761

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Update on Prostate Cancer Diagnosis, Prognosis and Prediction to Response to Therapy)

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15 pages, 1805 KiB

Open AccessReview

New Frontiers in Prostate Cancer Treatment: Are We Ready for Drug Combinations with Novel Agents?

by Gaetano Aurilio, Alessia Cimadamore, Matteo Santoni, Franco Nolè, Marina Scarpelli, Francesco Massari, Antonio Lopez-Beltran, Liang Cheng and Rodolfo Montironi

Cells 2020, 9(6), 1522; https://doi.org/10.3390/cells9061522 - 22 Jun 2020

Cited by 6 | Viewed by 3239

Abstract

Medical treatment for metastatic castration-resistant prostate cancer (mCRPC) patients has progressively been evolving from a nonspecific clinical approach to genomics-oriented therapies. The scientific community is in fact increasingly focusing on developing DNA damage repair (DDR) defect-driven novel molecules, both as single-agent therapy and [...] Read more.

Medical treatment for metastatic castration-resistant prostate cancer (mCRPC) patients has progressively been evolving from a nonspecific clinical approach to genomics-oriented therapies. The scientific community is in fact increasingly focusing on developing DNA damage repair (DDR) defect-driven novel molecules, both as single-agent therapy and in combined treatment strategies. Accordingly, research is under way into combined drug therapies targeting different pathways, e.g. androgen receptor signaling (ARS) and poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) enzymes, immune checkpoint (IC) and PARP, IC, and ARS, and prostate-specific membrane antigen (PSMA). In an attempt to formulate evolving treatment paradigms in mCRPC patients, here we selected clinical research into patients undergoing therapies with emerging molecules, with particular emphasis towards PARP-, IC-, and PSMA-inhibitors. In order to focus on those molecules and drug combinations most likely to be translated into routine clinical care in the near future, we selected only those clinical studies currently recruiting patients. A PubMed search focusing on the keywords “prostate cancer”, “metastatic castration-resistant prostate cancer”, “DDR pathways”, “ARS inhibitors”, “PARP inhibitors”, “IC inhibitors”, “PSMA-targeting agents”, and “drug combinations” was performed. Full article

(This article belongs to the Special Issue Update on Prostate Cancer Diagnosis, Prognosis and Prediction to Response to Therapy)

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18 pages, 649 KiB

Open AccessReview

Update on Circulating Tumor Cells in Genitourinary Tumors with Focus on Prostate Cancer

by Alessia Cimadamore, Gaetano Aurilio, Franco Nolé, Francesco Massari, Marina Scarpelli, Matteo Santoni, Antonio Lopez-Beltran, Liang Cheng and Rodolfo Montironi

Cells 2020, 9(6), 1495; https://doi.org/10.3390/cells9061495 - 19 Jun 2020

Cited by 8 | Viewed by 2838

Abstract

Current developments in the treatment of genitourinary tumors underline the unmet clinical need for biomarkers to improve decision-making in a challenging clinical setting. The detection of circulating tumor cells (CTCs) has become one of the most exciting and important new approaches to identifying [...] Read more.

Current developments in the treatment of genitourinary tumors underline the unmet clinical need for biomarkers to improve decision-making in a challenging clinical setting. The detection of circulating tumor cells (CTCs) has become one of the most exciting and important new approaches to identifying biomarkers at different stages of disease in a non-invasive way. Potential applications of CTCs include monitoring treatment efficacy and early detection of progression, selecting tailored therapies, as well as saving treatment costs. However, despite the promising implementation of CTCs in a clinical scenario, the isolation and characterization of these cells for molecular studies remain expensive with contemporary platforms, and significant technical challenges still need to be overcome. This updated, critical review focuses on the state of CTCs in patients with genitourinary tumor with focus on prostate cancer, discussing technical issues, main clinical results and hypothesizing potential future perspectives in clinical scenarios. Full article

(This article belongs to the Special Issue Update on Prostate Cancer Diagnosis, Prognosis and Prediction to Response to Therapy)

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15 pages, 5575 KiB

Open AccessReview

Morphologic, Molecular and Clinical Features of Aggressive Variant Prostate Cancer

by Rodolfo Montironi, Alessia Cimadamore, Antonio Lopez-Beltran, Marina Scarpelli, Gaetano Aurilio, Matteo Santoni, Francesco Massari and Liang Cheng

Cells 2020, 9(5), 1073; https://doi.org/10.3390/cells9051073 - 25 Apr 2020

Cited by 33 | Viewed by 5766

Abstract

The term aggressive variant prostate cancer (AVPCa) refers to androgen receptor (AR)-independent anaplastic forms of prostate cancer (PCa), clinically characterized by a rapidly progressive disease course. This involves hormone refractoriness and metastasis in visceral sites. Morphologically, AVPCa is made up of solid sheets [...] Read more.

The term aggressive variant prostate cancer (AVPCa) refers to androgen receptor (AR)-independent anaplastic forms of prostate cancer (PCa), clinically characterized by a rapidly progressive disease course. This involves hormone refractoriness and metastasis in visceral sites. Morphologically, AVPCa is made up of solid sheets of cells devoid of pleomorphism, with round and enlarged nuclei with prominent nucleoli and slightly basophilic cytoplasm. The cells do not show the typical architectural features of prostatic adenocarcinoma and mimic the undifferentiated carcinoma of other organs and locations. The final diagnosis is based on the immunohistochemical expression of markers usually seen in the prostate, such as prostate-specific membrane antigen (PSMA). A subset of AVPCa can also express neuroendocrine (NE) markers such as chromogranin A, synaptophysin and CD56. This letter subset represents an intermediate part of the spectrum of NE tumors which ranges from small cell to large cell carcinoma. All such tumors can develop following potent androgen receptor pathway inhibition. This means that castration-resistant prostate cancer (CRPCa) transdifferentiates and becomes a treatment-related NE PCa in a clonally divergent manner. The tumors that do not show NE differentiation might harbor somatic and/or germline alterations in the DNA repair pathway. The identification of these subtypes has direct clinical relevance with regard to the potential benefit of platinum-based chemotherapy, poly (ADP-ribose) polymerase inhibitors and likely further therapies. Full article

(This article belongs to the Special Issue Update on Prostate Cancer Diagnosis, Prognosis and Prediction to Response to Therapy)

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