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Advances in Molecular Research on Prostate Cancer
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Advances in Molecular Research on Prostate Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 37017

Special Issue Editors

Prof. Dr. Gian Maria Busetto

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Guest Editor
Sapienza University of Rome, Rome, Italy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Alessandro Sciarra

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Guest Editor
Sapienza University of Rome, Rome, Italy
Dr. Angelo Porreca

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Guest Editor
IOV - Istituto Oncologico Veneto – IRCCS, Via Gattamelata, 64, 35128 Padova, Italy
Interests: renal cell carcinoma; prostate cancer; bladder cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Matteo Ferro

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Guest Editor
Division of Urology, European Institute of Oncology-IRCCS, 20141 Milan, Italy
Interests: cancer cells; cancer biology; prostate cancer; urology; prostate; bladder cancer; urologic oncology; cancer metastasis; oncology; doppler ultrasonography
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ettore De Berardinis

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Guest Editor
Sapienza University of Rome, Rome, Italy

Special Issue Information

Dear Colleagues,

Prostate cancer (PC) is the second most diagnosed cancer in men. Nowadays, early detection of PC is mainly carried out testing prostate-specific antigen (PSA) level in blood. Regrettably, PSA cannot discriminate patients with benign prostatic hyperplasia (BPH) and clinically significant forms of PC. Prognosis and follow-up of PC are even affected by several limitations, including absence of reliable bio-markers.  Recent reports suggest that new tools for the diagnosis, prognosis and management of PC may be provided by metabolomic studies as shown by preliminary data on sarcosine. To date, two different metabolomics approaches have been commonly carried out, namely targeted and untargeted, on prostate tissue and bio-fluids. But metabolomics is not the only valuable tool to discover new disease-associated markers; in fact, changes in the concentration of metabolites in bio-fluids are reflective of alterations in the physiological status of an individual. Other important field of research are represented by circulating tumor cells (CTC), exosomes, miRNAs, etc. Many genetic alterations in prostate cancer have been identified and may be a target to further evaluate the natural history of PC.

Prof. Dr. Gian Maria Busetto
Prof. Dr. Alessandro Sciarra
Dr. Matteo Ferro
Prof. Dr. Ettore De Berardinis
Guest Editors

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Published Papers (7 papers)

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Research

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9 pages, 1235 KiB  
Article
Foggia Prostate Cancer Risk Calculator 2.0: A Novel Risk Calculator including MRI and Bladder Outlet Obstruction Parameters to Reduce Unnecessary Biopsies
by Ugo Giovanni Falagario, Gian Maria Busetto, Marco Recchia, Edoardo Tocci, Oscar Selvaggio, Antonella Ninivaggi, Paola Milillo, Luca Macarini, Francesca Sanguedolce, Vito Mancini, Pasquale Annese, Carlo Bettocchi, Giuseppe Carrieri and Luigi Cormio
Int. J. Mol. Sci. 2023, 24(3), 2449; https://doi.org/10.3390/ijms24032449 - 26 Jan 2023
Viewed by 1845
Abstract
Risk calculator (RC) combining PSA with other clinical information can help to better select patients at risk of prostate cancer (PCa) for prostate biopsy. The present study aimed to develop a new Pca RC, including MRI and bladder outlet obstruction parameters (BOOP). The [...] Read more.
Risk calculator (RC) combining PSA with other clinical information can help to better select patients at risk of prostate cancer (PCa) for prostate biopsy. The present study aimed to develop a new Pca RC, including MRI and bladder outlet obstruction parameters (BOOP). The ability of these parameters in predicting PCa and clinically significant PCa (csPCa: ISUP GG ≥ 2) was assessed by binary logistic regression. A total of 728 patients were included from two institutions. Of these, 395 (54.3%) had negative biopsies and 161 (22.11%) and 172 (23.6%) had a diagnosis of ISUP GG1 PCa and csPCa. The two RC ultimately included age, PSA, DRE, prostate volume (pVol), post-voided residual urinary volume (PVR), and PIRADS score. Regarding BOOP, higher prostate volumes (csPCa: OR 0.98, CI 0.97,0.99) and PVR ≥ 50 mL (csPCa: OR 0.27, CI 0.15, 0.47) were protective factors for the diagnosis of any PCa and csPCa. AUCs after internal validation were 0.78 (0.75, 0.82) and 0.82 (0.79, 0.86), respectively. Finally, decision curves analysis demonstrated higher benefit compared to the first-generation calculator and MRI alone. These novel RC based on MRI and BOOP may help to better select patient for prostate biopsy after prostate MRI. Full article
(This article belongs to the Special Issue Advances in Molecular Research on Prostate Cancer)
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19 pages, 3857 KiB  
Article
An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes
by Heike Thiemeyer, Leila Taher, Jan Torben Schille, Eva-Maria Packeiser, Lisa K. Harder, Marion Hewicker-Trautwein, Bertram Brenig, Ekkehard Schütz, Julia Beck, Ingo Nolte and Hugo Murua Escobar
Int. J. Mol. Sci. 2021, 22(21), 11481; https://doi.org/10.3390/ijms222111481 - 25 Oct 2021
Cited by 11 | Viewed by 3288
Abstract
Prostate cancer (PCa) in dogs is a highly malignant disease akin to its human counterpart. In contrast to the situation in humans, multi-gene approaches facilitating risk stratification of canine PCa are barely established. The aims of this study were the characterization of the [...] Read more.
Prostate cancer (PCa) in dogs is a highly malignant disease akin to its human counterpart. In contrast to the situation in humans, multi-gene approaches facilitating risk stratification of canine PCa are barely established. The aims of this study were the characterization of the transcriptional landscape of canine PCa and the identification of diagnostic, prognostic and/or therapeutic biomarkers through a multi-step screening approach. RNA-Sequencing of ten malignant tissues and fine-needle aspirations (FNA), and 14 nonmalignant tissues and FNAs was performed to find differentially expressed genes (DEGs) and deregulated pathways. The 4098 observed DEGs were involved in 49 pathways. These 49 pathways could be grouped into five superpathways summarizing the hallmarks of canine PCa: (i) inflammatory response and cytokines; (ii) regulation of the immune system and cell death; (iii) cell surface and PI3K signaling; (iv) cell cycle; and (v) phagosome and autophagy. Among the highly deregulated, moderately to strongly expressed DEGs that were members of one or more superpathways, 169 DEGs were listed in relevant databases and/or the literature and included members of the PCa pathway, oncogenes, prostate-specific genes, and druggable genes. These genes are novel and promising candidate diagnostic, prognostic and/or therapeutic canine PCa biomarkers. Full article
(This article belongs to the Special Issue Advances in Molecular Research on Prostate Cancer)
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Review

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12 pages, 765 KiB  
Review
CRISPR Screen Contributes to Novel Target Discovery in Prostate Cancer
by Takuya Tsujino, Kazumasa Komura, Teruo Inamoto and Haruhito Azuma
Int. J. Mol. Sci. 2021, 22(23), 12777; https://doi.org/10.3390/ijms222312777 - 26 Nov 2021
Cited by 20 | Viewed by 8563
Abstract
Prostate cancer (PCa) is one of the common malignancies in male adults. Recent advances in omics technology, especially in next-generation sequencing, have increased the opportunity to identify genes that correlate with cancer diseases, including PCa. In addition, a genetic screen based on CRISPR/Cas9 [...] Read more.
Prostate cancer (PCa) is one of the common malignancies in male adults. Recent advances in omics technology, especially in next-generation sequencing, have increased the opportunity to identify genes that correlate with cancer diseases, including PCa. In addition, a genetic screen based on CRISPR/Cas9 technology has elucidated the mechanisms of cancer progression and drug resistance, which in turn has enabled the discovery of new targets as potential genes for new therapeutic targets. In the era of precision medicine, such knowledge is crucial for clinicians in their decision-making regarding patient treatment. In this review, we focus on how CRISPR screen for PCa performed to date has contributed to the identification of biologically critical and clinically relevant target genes. Full article
(This article belongs to the Special Issue Advances in Molecular Research on Prostate Cancer)
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14 pages, 1008 KiB  
Review
Active Surveillance in Prostate Cancer: Role of Available Biomarkers in Daily Practice
by Belén Pastor-Navarro, José Rubio-Briones, Ángel Borque-Fernando, Luis M. Esteban, Jose Luis Dominguez-Escrig and José Antonio López-Guerrero
Int. J. Mol. Sci. 2021, 22(12), 6266; https://doi.org/10.3390/ijms22126266 - 10 Jun 2021
Cited by 14 | Viewed by 3651
Abstract
Prostate cancer (PCa) is the most commonly diagnosed cancer in men. The diagnosis is currently based on PSA levels, which are associated with overdiagnosis and overtreatment. Moreover, most PCas are localized tumours; hence, many patients with low-/very low-risk PCa could benefit from active [...] Read more.
Prostate cancer (PCa) is the most commonly diagnosed cancer in men. The diagnosis is currently based on PSA levels, which are associated with overdiagnosis and overtreatment. Moreover, most PCas are localized tumours; hence, many patients with low-/very low-risk PCa could benefit from active surveillance (AS) programs instead of more aggressive, active treatments. Heterogeneity within inclusion criteria and follow-up strategies are the main controversial issues that AS presently faces. Many biomarkers are currently under investigation in this setting; however, none has yet demonstrated enough diagnostic ability as an independent predictor of pathological or clinical progression. This work aims to review the currently available literature on tissue, blood and urine biomarkers validated in clinical practice for the management of AS patients. Full article
(This article belongs to the Special Issue Advances in Molecular Research on Prostate Cancer)
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15 pages, 640 KiB  
Review
Circulating Tumor DNA Testing for Homology Recombination Repair Genes in Prostate Cancer: From the Lab to the Clinic
by Alessia Cimadamore, Liang Cheng, Francesco Massari, Matteo Santoni, Laura Pepi, Carmine Franzese, Marina Scarpelli, Antonio Lopez-Beltran, Andrea Benedetto Galosi and Rodolfo Montironi
Int. J. Mol. Sci. 2021, 22(11), 5522; https://doi.org/10.3390/ijms22115522 - 24 May 2021
Cited by 13 | Viewed by 4093
Abstract
Approximately 23% of metastatic castration-resistant prostate cancers (mCRPC) harbor deleterious aberrations in DNA repair genes. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) therapy has shown improvements in overall survival in patients with mCRPC who harbor somatic and/or germline alterations of homology recombination repair (HRR) [...] Read more.
Approximately 23% of metastatic castration-resistant prostate cancers (mCRPC) harbor deleterious aberrations in DNA repair genes. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) therapy has shown improvements in overall survival in patients with mCRPC who harbor somatic and/or germline alterations of homology recombination repair (HRR) genes. Peripheral blood samples are typically used for the germline mutation analysis test using the DNA extracted from peripheral blood leucocytes. Somatic alterations can be assessed by extracting DNA from a tumor tissue sample or using circulating tumor DNA (ctDNA) extracted from a plasma sample. Each of these genetic tests has its own benefits and limitations. The main advantages compared to the tissue test are that liquid biopsy is a non-invasive and easily repeatable test with the value of better representing tumor heterogeneity than primary biopsy and of capturing changes and/or resistance mutations in the genetic tumor profile during disease progression. Furthermore, ctDNA can inform about mutation status and guide treatment options in patients with mCRPC. Clinical validation and test implementation into routine clinical practice are currently very limited. In this review, we discuss the state of the art of the ctDNA test in prostate cancer compared to blood and tissue testing. We also illustrate the ctDNA testing workflow, the available techniques for ctDNA extraction, sequencing, and analysis, describing advantages and limits of each techniques. Full article
(This article belongs to the Special Issue Advances in Molecular Research on Prostate Cancer)
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17 pages, 354 KiB  
Review
Biomarkers in Prostate Cancer Diagnosis: From Current Knowledge to the Role of Metabolomics and Exosomes
by Stefano Salciccia, Anna Laura Capriotti, Aldo Laganà, Stefano Fais, Mariantonia Logozzi, Ettore De Berardinis, Gian Maria Busetto, Giovanni Battista Di Pierro, Gian Piero Ricciuti, Francesco Del Giudice, Alessandro Sciarra, Peter R. Carroll, Matthew R. Cooperberg, Beatrice Sciarra and Martina Maggi
Int. J. Mol. Sci. 2021, 22(9), 4367; https://doi.org/10.3390/ijms22094367 - 22 Apr 2021
Cited by 69 | Viewed by 6461
Abstract
Early detection of prostate cancer (PC) is largely carried out using assessment of prostate-specific antigen (PSA) level; yet it cannot reliably discriminate between benign pathologies and clinically significant forms of PC. To overcome the current limitations of PSA, new urinary and serum biomarkers [...] Read more.
Early detection of prostate cancer (PC) is largely carried out using assessment of prostate-specific antigen (PSA) level; yet it cannot reliably discriminate between benign pathologies and clinically significant forms of PC. To overcome the current limitations of PSA, new urinary and serum biomarkers have been developed in recent years. Although several biomarkers have been explored in various scenarios and patient settings, to date, specific guidelines with a high level of evidence on the use of these markers are lacking. Recent advances in metabolomic, genomics, and proteomics have made new potential biomarkers available. A number of studies focused on the characterization of the specific PC metabolic phenotype using different experimental approaches has been recently reported; yet, to date, research on metabolomic application for PC has focused on a small group of metabolites that have been known to be related to the prostate gland. Exosomes are extracellular vesicles that are secreted from all mammalian cells and virtually detected in all bio-fluids, thus allowing their use as tumor biomarkers. Thanks to a general improvement of the technical equipment to analyze exosomes, we are able to obtain reliable quantitative and qualitative information useful for clinical application. Although some pilot clinical investigations have proposed potential PC biomarkers, data are still preliminary and non-conclusive. Full article
(This article belongs to the Special Issue Advances in Molecular Research on Prostate Cancer)
15 pages, 1004 KiB  
Review
Treating Prostate Cancer by Antibody–Drug Conjugates
by Matteo Rosellini, Matteo Santoni, Veronica Mollica, Alessandro Rizzo, Alessia Cimadamore, Marina Scarpelli, Nadia Storti, Nicola Battelli, Rodolfo Montironi and Francesco Massari
Int. J. Mol. Sci. 2021, 22(4), 1551; https://doi.org/10.3390/ijms22041551 - 4 Feb 2021
Cited by 67 | Viewed by 7749
Abstract
Prostate cancer is the most frequent malignancy in the worldwide male population; it is also one of the most common among all the leading cancer-related death causes. In the last two decades, the therapeutic scenario of metastatic castration-resistant prostate cancer has been enriched [...] Read more.
Prostate cancer is the most frequent malignancy in the worldwide male population; it is also one of the most common among all the leading cancer-related death causes. In the last two decades, the therapeutic scenario of metastatic castration-resistant prostate cancer has been enriched by the use of chemotherapy and androgen receptor signaling inhibitors (ARSI) and, more recently, by immunotherapy and poly(ADP–ribose) polymerase (PARP) inhibitors. At the same time, several trials have shown the survival benefits related to the administration of novel ARSIs among patients with non-castration-resistant metastatic disease along with nonmetastatic castration-resistant cancer too. Consequently, the therapeutic course of this malignancy has been radically expanded, ensuring survival benefits never seen before. Among the more recently emerging agents, the so-called “antibody–drug conjugates” (ADCs) are noteworthy because of their clinical practice changing outcomes obtained in the management of other malignancies (including breast cancer). The ADCs are novel compounds consisting of cytotoxic agents (also known as the payload) linked to specific antibodies able to recognize antigens expressed over cancer cells’ surfaces. As for prostate cancer, researchers are focusing on STEAP1, TROP2, PSMA, CD46 and B7-H3 as optimal antigens which may be targeted by ADCs. In this paper, we review the pivotal trials that have currently changed the therapeutic approach to prostate cancer, both in the nonmetastatic castration-resistant and metastatic settings. Therefore, we focus on recently published and ongoing trials designed to investigate the clinical activity of ADCs against prostate malignancy, characterizing these agents. Lastly, we briefly discuss some ADCs-related issues with corresponding strategies to overwhelm them, along with future perspectives for these promising novel compounds. Full article
(This article belongs to the Special Issue Advances in Molecular Research on Prostate Cancer)
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