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  1. Article: PARP inhibitor combinations in prostate cancer.

    Pezaro, Carmel

    Therapeutic advances in medical oncology

    2020  Volume 12, Page(s) 1758835919897537

    Abstract: Polyadenosine-diphosphate-ribose polymerase (PARP) inhibitors cause deoxyribonucleic acid (DNA) damage that can be lethal to cells with deficient repair mechanisms. A number of PARP inhibitors are being tested as treatments for men with prostate cancer, ... ...

    Abstract Polyadenosine-diphosphate-ribose polymerase (PARP) inhibitors cause deoxyribonucleic acid (DNA) damage that can be lethal to cells with deficient repair mechanisms. A number of PARP inhibitors are being tested as treatments for men with prostate cancer, both as monotherapies and in combinations that are based on purported synergies in treatment effect. While the initial single-agent development focused on men with identified deficiencies in DNA-repair pathways, broader patient populations are being considered for combination approaches. This review summarizes the current clinical development of PARP inhibitors and explores the rationale for novel combination strategies.
    Language English
    Publishing date 2020-03-18
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2503443-1
    ISSN 1758-8359 ; 1758-8340
    ISSN (online) 1758-8359
    ISSN 1758-8340
    DOI 10.1177/1758835919897537
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Living Longer and Better with Advanced Prostate Cancer.

    Mukherji, Deborah / Omlin, Aurelius / Pezaro, Carmel

    European urology

    2020  Volume 78, Issue 3, Page(s) 358–359

    MeSH term(s) Humans ; Male ; Phenylthiohydantoin/analogs & derivatives ; Prostatic Neoplasms/therapy ; Prostatic Neoplasms, Castration-Resistant
    Chemical Substances Phenylthiohydantoin (2010-15-3) ; enzalutamide (93T0T9GKNU)
    Language English
    Publishing date 2020-06-15
    Publishing country Switzerland
    Document type Editorial ; Comment
    ZDB-ID 193790-x
    ISSN 1873-7560 ; 1421-993X ; 0302-2838
    ISSN (online) 1873-7560 ; 1421-993X
    ISSN 0302-2838
    DOI 10.1016/j.eururo.2020.05.020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MO 294: Show issues

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  3. Article ; Online: Sorting Through the Maze of Treatment Options for Metastatic Castration-Sensitive Prostate Cancer.

    Schulte, Brian / Morgans, Alicia K / Shore, Neal D / Pezaro, Carmel

    American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

    2020  Volume 40, Page(s) 1–10

    Abstract: Since 1944, when Huggins and Hodges demonstrated the effectiveness of bilateral orchiectomy for metastatic prostate cancer (PCa), androgen deprivation therapy (ADT) has been the first-line treatment for men with advanced PCa. The proportion of PCa cases ... ...

    Abstract Since 1944, when Huggins and Hodges demonstrated the effectiveness of bilateral orchiectomy for metastatic prostate cancer (PCa), androgen deprivation therapy (ADT) has been the first-line treatment for men with advanced PCa. The proportion of PCa cases that are metastatic at diagnosis ranges globally, from 5%-20% in countries with widespread screening practices to upward of 30%-60% where screening is minimal. In the United States alone, there will be an estimated 191,000 new cases of PCa diagnosed in the year 2020, of which approximately 20% will be metastatic.
    MeSH term(s) Humans ; Male ; Neoplasm Metastasis ; Prostatic Neoplasms, Castration-Resistant/therapy
    Language English
    Publishing date 2020-03-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2431126-1
    ISSN 1548-8756 ; 1548-8748
    ISSN (online) 1548-8756
    ISSN 1548-8748
    DOI 10.1200/EDBK_278845
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Putting guidelines into practice: has the era of perioperative chemotherapy arrived?

    Georgiou, Chloe L / Pezaro, Carmel / Sengupta, Shomik

    Translational andrology and urology

    2018  Volume 7, Issue Suppl 2, Page(s) S255–S257

    Language English
    Publishing date 2018-06-05
    Publishing country China
    Document type Editorial ; Comment
    ZDB-ID 2851630-8
    ISSN 2223-4691 ; 2223-4691 ; 2223-4683
    ISSN (online) 2223-4691
    ISSN 2223-4691 ; 2223-4683
    DOI 10.21037/tau.2018.04.02
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The Winds of Change: Emerging Therapeutics in Prostate Cancer.

    Pezaro, Carmel J / Marciscano, Ariel E / Madan, Ravi A

    American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

    2018  Volume 38, Page(s) 382–390

    Abstract: The last decade has seen substantial advances in androgen receptor targeting in prostate cancer. In addition, advances have been made in immunotherapy and radiopharmaceutical-based therapy, although their optimal use in the clinic remains unclear. Recent ...

    Abstract The last decade has seen substantial advances in androgen receptor targeting in prostate cancer. In addition, advances have been made in immunotherapy and radiopharmaceutical-based therapy, although their optimal use in the clinic remains unclear. Recent understanding of the relevance and actionability of DNA damage repair mutations in a considerable minority of patients with prostate cancer is likely to open up a new frontier in prostate cancer therapeutics. As androgen receptor-directed therapy moves earlier in the disease process for prostate cancer, advances in these nonandrogen receptor-based therapeutics may take on greater significance in the years to come.
    MeSH term(s) Clinical Trials as Topic ; Combined Modality Therapy/methods ; DNA Repair/drug effects ; Disease Management ; Humans ; Immunotherapy ; Male ; Mutation ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Poly(ADP-ribose) Polymerases/genetics ; Poly(ADP-ribose) Polymerases/metabolism ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/mortality ; Prostatic Neoplasms/therapy ; Radiopharmaceuticals/pharmacology ; Radiopharmaceuticals/therapeutic use ; Treatment Outcome
    Chemical Substances Poly(ADP-ribose) Polymerase Inhibitors ; Radiopharmaceuticals ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30)
    Language English
    Publishing date 2018-09-19
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1548-8756 ; 1092-9118 ; 1548-8748
    ISSN (online) 1548-8756
    ISSN 1092-9118 ; 1548-8748
    DOI 10.1200/EDBK_201295
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Effects of estrogen receptor signaling on prostate cancer carcinogenesis.

    Qu, Liang G / Wardan, Hady / Davis, Ian D / Pezaro, Carmel / Sluka, Pavel

    Translational research : the journal of laboratory and clinical medicine

    2020  Volume 222, Page(s) 56–66

    Abstract: Management of advanced prostate cancer remains complex, with substantial changes in treatment options emerging in recent years having implications for treatment selection and sequencing. Recognition of the importance of androgen signaling has led to life- ...

    Abstract Management of advanced prostate cancer remains complex, with substantial changes in treatment options emerging in recent years having implications for treatment selection and sequencing. Recognition of the importance of androgen signaling has led to life-prolonging treatments, as well as "liquid biopsy" techniques to guide these treatments in some settings. Therapies that target estrogen receptor signaling are efficacious but infrequently used options for treatment of castration-resistant prostate cancer. It is possible that nuances of estrogen receptor (ER) signaling, or selective modulation of ER signaling, might favorably influence outcomes in castration-resistant prostate cancer. Expression of ERs and their variants has been investigated in other cancers such as breast. Constitutively activating gene alterations can potentially lead to ER activation and subsequently promote cancer progression. The identification of these aberrations may help identify cancer phenotypes that are susceptible or resistant to therapies involved in ER signaling. This review outlines the current literature regarding ER signaling in prostate cancer, and provides background for exploration of potentially useful ER signaling biomarkers in advanced prostate cancer.
    MeSH term(s) Carcinogenesis/metabolism ; Humans ; Liquid Biopsy ; Male ; Prostatic Neoplasms/metabolism ; RNA Splicing/genetics ; Receptors, Estrogen/genetics ; Receptors, Estrogen/metabolism ; Signal Transduction
    Chemical Substances Receptors, Estrogen
    Language English
    Publishing date 2020-05-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2246684-8
    ISSN 1878-1810 ; 1532-6543 ; 1931-5244
    ISSN (online) 1878-1810 ; 1532-6543
    ISSN 1931-5244
    DOI 10.1016/j.trsl.2020.04.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Identification of novel oncogenic events occurring early in prostate carcinogenesis using purified autologous malignant and non-malignant prostate epithelial cells.

    Sluka, Pavel / Pezaro, Carmel / Wardan, Hady / Sengupta, Shomik / Davis, Ian D

    BJU international

    2019  Volume 123 Suppl 5, Page(s) 27–35

    Abstract: Objective: To interrogate enriched prostate cancer cells and autologous non-malignant prostate epithelial cells from men with localized prostate cancer, in order to identify early oncogenic pathways.: Patients and methods: We collected malignant and ... ...

    Abstract Objective: To interrogate enriched prostate cancer cells and autologous non-malignant prostate epithelial cells from men with localized prostate cancer, in order to identify early oncogenic pathways.
    Patients and methods: We collected malignant and matched non-malignant prostatectomy samples from men with adenocarcinoma involving two or more contiguous areas in only one lobe of the prostate. Tissue samples from both lobes were subjected to digestion and single-cell suspensions were prepared. Epithelial cell adhesion molecule-positive cells from cancerous and contralateral non-malignant (control) samples were isolated using magnetic beads, ensuring uniform populations were obtained for each donor. Unbiased RNA sequencing analysis was used to measure gene expression and for detection of transcribed mutations or splice variants that were over- or under-represented in malignant prostate epithelial cells relative to autologous control prostate epithelial cells.
    Results: From five patient samples we identified 17 genes that were altered in prostate cancer epithelial cells, with 82% of genes being downregulated. Three genes, TDRD1, ANGTL4, and CLDN3, were consistently upregulated in malignant tissue. Malignant cells from three of the five patients showed evidence of upregulated ERG signalling, however, only one of these contained a TMPRSS2-ERG rearrangement. We did not identify mutations, gene rearrangements, or splice variants that were consistent amongst the patients.
    Conclusions: Events occurring early in prostate cancer oncogenesis in these samples were characterized by a predominant downregulation of gene expression along with upregulation of TDRD1, ANGTL4 and CLDN3. No consistent mutations or splice variants were observed, but upregulation of ERG signalling was seen both in the presence and absence of the classic TMPRSS2-ERG rearrangement.
    MeSH term(s) Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Adenocarcinoma/surgery ; Aged ; Angiopoietin-like 4 Protein/genetics ; Carcinogenesis/genetics ; Cell Cycle Proteins/genetics ; Claudin-3/genetics ; Down-Regulation ; Epithelial Cells/pathology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Rearrangement ; Humans ; Male ; Middle Aged ; Prostatectomy ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/surgery ; RNA, Spliced Leader/physiology ; Serine Endopeptidases/genetics ; Signal Transduction ; Transcriptional Regulator ERG/genetics ; Up-Regulation
    Chemical Substances ANGPTL4 protein, human ; Angiopoietin-like 4 Protein ; CLDN3 protein, human ; Cell Cycle Proteins ; Claudin-3 ; RNA, Spliced Leader ; TDRD1 protein, human ; Transcriptional Regulator ERG ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
    Language English
    Publishing date 2019-02-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1462191-5
    ISSN 1464-410X ; 1464-4096 ; 1358-8672
    ISSN (online) 1464-410X
    ISSN 1464-4096 ; 1358-8672
    DOI 10.1111/bju.14695
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  8. Article ; Online: Circulating oestrogen receptor mutations and splice variants in advanced prostate cancer.

    Qu, Liang G / Wardan, Hady / Davis, Ian D / Iddawela, Mahesh / Sluka, Pavel / Pezaro, Carmel J

    BJU international

    2019  Volume 124 Suppl 1, Page(s) 50–56

    Abstract: Objective: To characterize circulating oestrogen receptor ( ER) mutants and splice variants in men with advanced prostate cancer.: Materials and methods: Sequential blood samples were obtained from men with advanced prostate cancer, and from healthy ... ...

    Abstract Objective: To characterize circulating oestrogen receptor ( ER) mutants and splice variants in men with advanced prostate cancer.
    Materials and methods: Sequential blood samples were obtained from men with advanced prostate cancer, and from healthy controls. Blood-derived RNA samples were analysed using droplet digital PCR for the presence of six ERα mutations (E380Q, L536Q, Y537C, Y537S, Y537N and D538G), and six ERα and ERβ splice variants (ERα-66, ERα-36, ERβ1, ERβ2, ERβ4 & ERβ5).
    Results: A total of 94 samples were collected from 42 men with advanced prostate cancer. Four mutations (E380Q, L536Q, Y537S and D538G) and all six splice variants were detected in patient samples. Splice variants were detectable in non-cancer control samples. The presence of ER mutations was associated with bone metastases and castration resistance. ERβ splice variant concentrations decreased after successive lines of treatment.
    Conclusions: The ER mutations were detectable in plasma from patients with advanced prostate cancer. ER splice variants were frequently detected in both men with and without prostate cancer.
    MeSH term(s) Aged ; Aged, 80 and over ; Alternative Splicing/genetics ; Alternative Splicing/physiology ; Australia ; Estrogen Receptor alpha/blood ; Estrogen Receptor alpha/genetics ; Estrogen Receptor beta/blood ; Estrogen Receptor beta/genetics ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Prospective Studies ; Prostatic Neoplasms/blood ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; RNA, Messenger/genetics
    Chemical Substances Estrogen Receptor alpha ; Estrogen Receptor beta ; RNA, Messenger
    Language English
    Publishing date 2019-10-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1462191-5
    ISSN 1464-410X ; 1464-4096 ; 1358-8672
    ISSN (online) 1464-410X
    ISSN 1464-4096 ; 1358-8672
    DOI 10.1111/bju.14797
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Prostate cancer in 2011: redefining the therapeutic landscape for CRPC.

    Pezaro, Carmel / Attard, Gerhardt

    Nature reviews. Urology

    2012  Volume 9, Issue 2, Page(s) 63–64

    MeSH term(s) Antineoplastic Agents/therapeutic use ; Combined Modality Therapy ; Humans ; Male ; Neoplasms, Hormone-Dependent/therapy ; Orchiectomy ; Prostatic Neoplasms/therapy
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2012-01-17
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2493737-X
    ISSN 1759-4820 ; 1759-4812
    ISSN (online) 1759-4820
    ISSN 1759-4812
    DOI 10.1038/nrurol.2011.235
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  10. Article ; Online: Clinical need for standardised multidisciplinary meeting assessment processes.

    Yau, Wing H / Devitt, Bianca / Aung, Soe Y / Parente, Phillip / Sharma, Sharad / Pezaro, Carmel

    Internal medicine journal

    2018  Volume 48, Issue 2, Page(s) 230–231

    MeSH term(s) Humans ; Patient Care Team ; Process Assessment (Health Care)
    Language English
    Publishing date 2018
    Publishing country Australia
    Document type Letter ; Comment
    ZDB-ID 2045436-3
    ISSN 1445-5994 ; 1444-0903
    ISSN (online) 1445-5994
    ISSN 1444-0903
    DOI 10.1111/imj.13688
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