Treatment of Metastatic Castration-resistant Prostate Cancer: Are PARP Inhibitors Shifting the Paradigm?

Fujimoto, Naohiro; Harada, Kiyoshi; Shiota, Masaki; Tomisaki, Ikko; Minato, Akinori; Nagata, Yoshika; Kimuro, Rieko; Harada, Mari; Fujisawa, Masato

doi:10.21873/anticanres.15282

Cited by 5 publications

(6 citation statements)

References 54 publications

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“…The prognosis of NEPC remains poor, with a median progression‐free survival and overall survival of 2–8 and 8–19 months, respectively 7 . Platinum‐ and etoposide‐based chemotherapy is commonly administered as first‐line treatment for NEPC 7‐9 . Fujimoto et al .…”

Section: Discussionmentioning

confidence: 99%

“…Fujimoto et al . summarized the available second‐line agents, which included amrubicin, irinotecan, docetaxel, everolimus, and olaparib, with several ongoing clinical trials being conducted on NEPC 7 . Given the lack of an established second‐line treatment, physicians should consider personalized treatment approaches for each patient with NEPC.…”

Section: Discussionmentioning

confidence: 99%

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Lethal disseminated intravascular coagulation induced by primary and metastatic neuroendocrine prostate cancer

Ando,

Sasaki,

Naito

2024

IJU Case Reports

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IntroductionNeuroendocrine prostate cancer has a poor prognosis. Although disseminated intravascular coagulation associated with malignancy can be lethal, it very rarely occurs among patients with primary neuroendocrine prostate cancer.Case presentationAn 80‐year‐old man presented to our hospital with bloody sputum. Blood examination indicated disseminated intravascular coagulation. Serum levels of prostate‐specific antigen and neuron‐specific enolase were 44.274 and 176 ng/mL, respectively. Core needle biopsies of an irregular mass in the prostate and a metastatic tumor in the left iliac bone showed similar neuroendocrine carcinoma cells. Hence, the patient was diagnosed with disseminated intravascular coagulation associated with primary and metastatic neuroendocrine prostate cancer. Unfortunately, he passed away 3 weeks after the biopsies.ConclusionGiven the difficulty of effectively treating metastatic neuroendocrine prostate cancer among patients in poor physical condition due to disease progression, identifying a new well‐tolerated treatment modality is imperative.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lethal disseminated intravascular coagulation induced by primary and metastatic neuroendocrine prostate cancer

Ando,

Sasaki,

Naito

2024

IJU Case Reports

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“…The side effects or treatment efficacy, which can influence the results, were not considered in the analysis. However, all of the patients in the cohort had been diagnosed with advanced urogenital cancer and their prognosis was generally a few years [ 7 , 21 , 22 ]. Therefore, we believe that the present study provided information related to chemotherapy with non-curative intent.…”

Section: Discussionmentioning

confidence: 99%

Change of genitourinary cancer patients’ perception and expectations over the course of pharmacotherapy

et al. 2022

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To determine the course of treatment while considering the patients’ desires, we examined trends regarding patients’ perception and expectations over the course of cancer pharmacotherapy. We retrospectively reviewed interview sheets filled in by patients with advanced urogenital cancers when they started a new pharmacotherapy regimen between 2014 and 2020. The responses to the following questions were analyzed: 1) How did your doctor explain the treatment objectives?; 2) Are you willing to receive treatment?; and 3) When the standard treatment becomes difficult to continue, would you like to try another treatment even if it may cause severe side effects? A total of 277 patients answered the interview sheet. The percentage of patients who accurately perceived the treatment objectives among patients receiving 1st, 2nd, and 3rd line regimens was 67%, 79%, and 93%, respectively. The percentage significantly improved over the course of pharmacotherapy (p = 0.0057). The percentage of patients who indicated that they were willing to receive treatment in 1st, 2nd, and 3rd line regimens was 80%, 83%, and 86%, respectively. The percentage of patients who indicated that they wanted to try another treatment when the standard treatment became difficult to continue in 1st, 2nd, and 3rd line regimens was 56%, 64%, and 59%, respectively. The percentage of patients who accurately perceived the objective of pharmacotherapy increased over the course of pharmacotherapy. The rate of patients who were willing to receive treatment and try other treatments when the standard treatment became too difficult to continue remained consistently high.

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“…On the other hand, in the metastatic scenario, there is a greater representation of mutation in the BRCA2 gene, with a frequency of 5.35%. [1][2][3][4][5]10,13,[15][16][17]19,[21][22][23][24][25][26]54,[59][60][61][62] In addition to the aforementioned germline alterations, somatic mutations (TP53, TMPRSS2, ETS fusion, and others) that drive tumor carcinogenesis can also be found 42. In addition, there is a particular interest in DNA repair pathway genes (BRCA1 and BRCA2).…”

Section: Somatic and Germline Mutations In Dna Genes Repairmentioning

confidence: 99%

Prostate Cancer and DNA Genes Repair: What Should an Oncologist Know? – A Narrative Review

Azevedo

Sá

Resende³

et al. 2022

OAIJMR

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Prostate cancer is a very prevalent disease in men, especially in Western countries. The treatment of this neoplasm, both localized and locally advanced, is based on the clinical risk analysis (Gleason, tumor size, PSA, and other factors) and is founded on surgery and/or radiotherapy with or without androgen blockade with a GnRH analog (hormone gonadotropin releaser). However, in patients who invariably progress to a metastatic disease scenario, the tumors may present a heterogeneous behavior, depending on whether or not they are sensitive to androgen blockade therapy. Due to the poor prognosis of the metastatic castration-resistant scenario, current research carried out in the molecular biology and genetics field has identified several gene alterations associated with the development of prostate cancer, which correlate with clinical risk, therapeutic predictive responses, and prognosis. Among the associated gene alterations, the genes of the DNA repair pathway are correlated with diseases that present: a higher risk of recurrence; early metastasis; worse cancer-specific survival; familial risk, and predictive responses to new targeted therapies. Therefore, the breast cancer susceptibility genes, BRCA1 and BRCA2 (and other variants), present in the DNA repair machinery are being investigated to provide more (and better) therapeutic options for the treatment of the disease in the advanced scenario. This review was aimed to describe the malignant prostate disease, especially with regard to DNA repair mechanisms, genomic analysis of prostate cancer, predictive and prognostic implications, as well as on the development of poly-(ADP-ribose) polymerase (PARP) inhibitors, synthetic lethality mechanisms, and BRCAness phenomenon.

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Treatment of Metastatic Castration-resistant Prostate Cancer: Are PARP Inhibitors Shifting the Paradigm?

Cited by 5 publications

References 54 publications

Lethal disseminated intravascular coagulation induced by primary and metastatic neuroendocrine prostate cancer

Lethal disseminated intravascular coagulation induced by primary and metastatic neuroendocrine prostate cancer

Change of genitourinary cancer patients’ perception and expectations over the course of pharmacotherapy

Prostate Cancer and DNA Genes Repair: What Should an Oncologist Know? – A Narrative Review

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