Advanced Prostate Cancer: Treatment Advances and Future Directions

Swami, Umang; McFarland, Taylor Ryan; Nussenzveig, Roberto; Agarwal, Neeraj

doi:10.1016/j.trecan.2020.04.010

Cited by 170 publications

(117 citation statements)

References 53 publications

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“…Prostate cancer (PCa) is the second most frequently diagnosed cancer (more than 1.3 million new cases worldwide in 2018) and the fifth leading cause of cancer deaths (over 350,000 deaths annually) in men [1]. The life-time risk of developing PCa is >10% [2], while the incidence of PCa between the ages of 65 to 74 is as high as 35.3% [3]. The mortality rate also rises with age, and 55% of PCa deaths occur over the age of 65 [1].…”

Section: Introductionmentioning

confidence: 99%

“…With advances in treatments, patients with localized PCa have a very good prognosis (five-year survival rate >99%). However, metastatic PCa patients only have a five-year survival rate just above 30% [2]. More importantly, a trend towards an increased PCa incidence and a doubling of mortality is estimated worldwide up to the year 2040, particularly affecting developing countries in Africa, Latin America, the Caribbean, and Asia [1].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target

Zhou

Carrera

et al. 2020

Cells

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Prostate cancer (PCa) is the most frequently diagnosed cancer in men, causing considerable morbidity and mortality. The P2X4 receptor (P2X4R) is the most ubiquitously expressed P2X receptor in mammals and is positively associated with tumorigenesis in many cancer types. However, its involvement in PCa progression is less understood. We hypothesized that P2X4R activity enhanced tumour formation by PCa cells. We showed that P2X4R was the most highly expressed, functional P2 receptor in these cells using quantitative reverse transcription PCR (RT-PCR) and a calcium influx assay. The effect of inhibiting P2X4R on PCa (PC3 and C4-2B4 cells) viability, proliferation, migration, invasion, and apoptosis were examined using the selective P2XR4 antagonists 5-BDBD and PSB-12062. The results demonstrated that inhibiting P2X4R impaired the growth and mobility of PCa cells but not apoptosis. In BALB/c immunocompromised nude mice inoculated with human PC3 cells subcutaneously, 5-BDBD showed anti-tumourigenic effects. Finally, a retrospective analysis of P2RX4 expression in clinical datasets (GDS1439, GDS1746, and GDS3289) suggested that P2X4R was positively associated with PCa malignancy. These studies suggest that P2X4R has a role in enhancing PCa tumour formation and is a clinically targetable candidate for which inhibitors are already available and have the potential to suppress disease progression.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target

Zhou

Carrera

et al. 2020

Cells

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“…Metastatic castration-sensitive prostate cancer is typically treated in the first-line setting with androgen deprivation therapy in combination with either the chemotherapeutic drug docetaxel or a newer, orally active hormonal agent, such as abiraterone or enzalutamide (Swami et al 2020). Treatment resistance, however, is universal and associated with transdifferentiation to a small-cell neuroendocrine histology in ∼17% of cases (Aggarwal et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Treatment-emergent neuroendocrine prostate cancer with a germline BRCA2 mutation: identification of a candidate reversion mutation associated with platinum/PARP-inhibitor resistance

Pandya

Shah

Kaplan

et al. 2021

Cold Spring Harb Mol Case Stud

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Neuroendocrine prostate cancer (NEPC) is a highly aggressive histologic subtype of prostate cancer associated with a poor prognosis. Its incidence is expected to increase as castration-resistant disease emerges from the widespread use of potent androgen receptor-targeting therapies, such as abiraterone and enzalutamide. Defects in homologous recombination repair genes, such as BRCA1/2 , are also being increasingly detected in individuals with advanced prostate cancer. We present the case of a 65-yr-old man with a germline BRCA2 mutation who developed explosive treatment-emergent, small-cell neuroendocrine prostate cancer. He achieved a complete response to platinum-containing chemotherapy, but a limited remission duration with the use of olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, as maintenance therapy. Upon relapse, tumor genomic profiling revealed a novel 228-bp deletion in exon 11 of the BRCA2 gene. The addition of the anti-PD1 drug pembrolizumab to olaparib was ineffective. This case highlights the ongoing challenges in treating neuroendocrine prostate cancer, even in the setting of homologous recombination repair deficiency.

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“…CRPC presents a broad spectrum of manifestations, ranging from no symptoms or evidence of metastasis (M0CRPC) to bone and visceral metastatization (mCRPC) with severe debilitation and poor survival [3].…”

Section: Introductionmentioning

confidence: 99%

Prognostic and Theranostic Applications of Positron Emission Tomography for a Personalized Approach to Metastatic Castration-Resistant Prostate Cancer

Filippi

Frantellizzi

Chiaravalloti

et al. 2021

IJMS

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Metastatic castration-resistant prostate cancer (mCRPC) represents a condition of progressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of manifestations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been profoundly modified by introducing novel therapeutic tools such as antiandrogen drugs (i.e., abiraterone acetate and enzalutamide), immunotherapy through sipuleucel-T, and targeted alpha therapy (TAT). This variety of approaches calls for unmet need of biomarkers suitable for patients’ pre-treatment selection and prognostic stratification. In this scenario, imaging with positron emission computed tomography (PET/CT) presents great and still unexplored potential to detect specific molecular and metabolic signatures, some of whom, such as the prostate specific membrane antigen (PSMA), can also be exploited as therapeutic targets, thus combining diagnosis and therapy in the so-called “theranostic” approach. In this review, we performed a web-based and desktop literature research to investigate the prognostic and theranostic potential of several PET imaging probes, such as 18F-FDG, 18F-choline and 68Ga-PSMA-11, also covering the emerging tracers still in a pre-clinical phase (e.g., PARP-inhibitors’ analogs and the radioligands binding to gastrin releasing peptide receptors/GRPR), highlighting their potential for defining personalized care pathways in mCRPC

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Advanced Prostate Cancer: Treatment Advances and Future Directions

Cited by 170 publications

References 53 publications

Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target

Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target

Treatment-emergent neuroendocrine prostate cancer with a germline BRCA2 mutation: identification of a candidate reversion mutation associated with platinum/PARP-inhibitor resistance

Prognostic and Theranostic Applications of Positron Emission Tomography for a Personalized Approach to Metastatic Castration-Resistant Prostate Cancer

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