Treatment Strategies for Metastatic Castration-Sensitive Prostate Cancer: From “All-Comers” to “Personalized” Approach

Harada, Kiyoshi; Shiota, Masaki; Minato, Akinori; Matsumoto, Masahiro; Tomisaki, Ikko; Fujisawa, Masato; Fujimoto, Naohiro

doi:10.2147/ott.s306345

Cited by 13 publications

(11 citation statements)

References 46 publications

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“…Notably, darolutamide was different in molecular structure from apalutamide and enzalutamide, leading to a different pharmaceutical outcome 3 . Although the treatment‐mediated manipulations on AR signaling initially show excellent anticancer effects, most tumors eventually recur and become fatal 2 . Several molecular mechanisms underlying the cellular resistance to AR‐signaling targeting therapies have been reported, including AR amplification and overexpression, AR mutations, AR co‐regulators, AR activation by intracellular signal transduction pathways, and AR variants 4–6 …”

Section: Introductionmentioning

confidence: 99%

“… 1 Recently, novel AR pathway inhibitors such as abiraterone, apalutamide, and enzalutamide in combination with androgen‐deprivation therapy have been proven to prolong survival for patients with metastatic hormone‐naïve prostate cancer. 2 In addition to apalutamide and enzalutamide, another second‐generation antiandrogen darolutamide has been shown to improve metastasis‐free survival and overall survival in nonmetastatic castration‐resistant prostate cancer. 3 Notably, darolutamide was different in molecular structure from apalutamide and enzalutamide, leading to a different pharmaceutical outcome.…”

Section: Introductionmentioning

confidence: 99%

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An oral first‐in‐class small molecule RSK inhibitor suppresses AR variants and tumor growth in prostate cancer

et al. 2022

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Ribosomal S6 kinase has been shown to play a key role in cellular resistance to endocrine therapy in prostate cancer through its regulation of YB‐1/androgen receptor (AR) signaling. PMD‐026, an oral first‐in‐class small molecule kinase inhibitor, is the first identified ribosomal S6 kinase inhibitor. This study investigated the effect of PMD‐026 on YB‐1/AR signaling and its antitumor effect in prostate cancer in vitro and in vivo. Castration‐resistant prostate cancer 22Rv1 cells that express high‐level AR variants were used in this study. The effect of PMD‐026 on YB‐1/AR signaling was investigated by quantitative real‐time PCR and western blot analysis. The effects of PMD‐026 on prostate cancer cells were investigated by cytotoxicity analysis, apoptosis assay, and cell cycle assay in vitro and a mouse castration model in vivo. PMD‐026 decreased YB‐1 phosphorylation as well as AR V7 mRNA and AR variant expressions in 22Rv1 cells. PMD‐026 suppressed cell proliferation alone and in combination with the second‐generation antiandrogens enzalutamide and darolutamide by inducing cellular apoptosis and G2/M arrest. In a mouse xenograft model, PMD‐026 suppressed tumor growth, and the combination of PMD‐026 and enzalutamide inhibited tumor growth more prominently than single treatments. Our results demonstrate an excellent antitumor effect of the novel ribosomal S6 kinase inhibitor PMD‐026 and the combination effect with the antiandrogen enzalutamide in castration‐resistant prostate cancer. These findings warrant a clinical trial of PMD‐026 in prostate cancer patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An oral first‐in‐class small molecule RSK inhibitor suppresses AR variants and tumor growth in prostate cancer

et al. 2022

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“…showed a possible treatment strategy for patients with mCSPC as per cancer and patient characteristics, as well as patient preference. 19 However, to date, the prognostic factors of upfront ARAT agents for Japanese patients with mCSPC have not been widely introduced into real‐world clinical practice. Collectively, further prognostication should be carried out to provide more precise information regarding the treatment of Japanese patients with mCSPC.…”

Section: Discussionmentioning

confidence: 99%

Useful predictors of progression‐free survival for Japanese patients with LATITUDE‐high‐risk metastatic castration‐sensitive prostate cancer who received upfront abiraterone acetate

et al. 2021

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Objective Recently, hormonal therapy using abiraterone acetate, a second‐generation androgen receptor axis‐targeted agent, was reported to improve overall survival and progression‐free survival in men with LATITUDE‐high‐risk metastatic castration‐sensitive prostate cancer. This observational multicenter study aimed to assess the efficacy of upfront abiraterone acetate in Japanese patients with LATITUDE‐high‐risk metastatic castration‐sensitive prostate cancer. Methods The present study included 112 Japanese patients with LATITUDE‐high‐risk metastatic castration‐sensitive prostate cancer who received upfront abiraterone acetate at four institutions belonging to the Tokai Urologic Oncology Research Seminar group, between January 2018 and September 2020. Progression‐free survival and overall survival were assessed, and Cox regression analyses were carried out to evaluate the prognostic significance of upfront abiraterone acetate for progression‐free survival. Results Within a median follow‐up period of 13 months, the progression‐free survival and overall survival rates were 76.8% and 89.3%, respectively. Both univariate and multivariable Cox regression analyses showed that the presence of Gleason pattern 5, performance status and hemoglobin were independent predictors of progression‐free survival. The patients were subsequently divided into three groups as follows: group 1, 17 patients negative for these three independent progression‐free survival predictors; group 2, 49 patients with one positive independent progression‐free survival predictor; and group 3, 45 patients with two or three independent progression‐free survival predictors. Progression‐free survival was significantly different among these three groups (P < 0.001). Conclusion Upfront abiraterone acetate might provide satisfactory outcomes for Japanese patients with LATITUDE‐high‐risk metastatic castration‐sensitive prostate cancer. Gleason pattern 5, performance status and hemoglobin are potential predictors of progression‐free survival in Japanese patients with LATITUDE‐high‐risk metastatic castration‐sensitive prostate cancer who received upfront abiraterone acetate.

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“…Editorial Comment to Effect of upfront combination therapy on the overall survival of patients with metastatic castration-sensitive prostate cancer: A multicenter retrospective study Upfront combination therapy using docetaxel or androgen receptor pathway inhibitors (ARPIs) prolongs radiographic progression-free survival (PFS) and overall survival (OS) in phase III clinical trials, and it has become a standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC). 1 However, the survival benefit by upfront combination therapy for mHSPC needs to be confirmed in real-world data among Japanese patients. Recently, Naiki et al 2 have investigated the outcome between androgen deprivation therapy (ADT) with bicalutamide and upfront abiraterone for high-risk mHSPC among Japanese patients with their characteristics balanced, and have reported superior PFS by upfront abiraterone.…”

Section: Editorial Commentmentioning

confidence: 99%

“…Upfront combination therapy using docetaxel or androgen receptor pathway inhibitors (ARPIs) prolongs radiographic progression‐free survival (PFS) and overall survival (OS) in phase III clinical trials, and it has become a standard treatment for metastatic hormone‐sensitive prostate cancer (mHSPC) 1 . However, the survival benefit by upfront combination therapy for mHSPC needs to be confirmed in real‐world data among Japanese patients.…”

mentioning

confidence: 99%

Editorial Comment to Effect of upfront combination therapy on the overall survival of patients with metastatic castration‐sensitive prostate cancer: A multicenter retrospective study

Treatment Strategies for Metastatic Castration-Sensitive Prostate Cancer: From “All-Comers” to “Personalized” Approach

Cited by 13 publications

References 46 publications

An oral first‐in‐class small molecule RSK inhibitor suppresses AR variants and tumor growth in prostate cancer

An oral first‐in‐class small molecule RSK inhibitor suppresses AR variants and tumor growth in prostate cancer

Useful predictors of progression‐free survival for Japanese patients with LATITUDE‐high‐risk metastatic castration‐sensitive prostate cancer who received upfront abiraterone acetate

Editorial Comment to Effect of upfront combination therapy on the overall survival of patients with metastatic castration‐sensitive prostate cancer: A multicenter retrospective study

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