Clinical Efficacy of Enzalutamide vs Bicalutamide Combined With Androgen Deprivation Therapy in Men With Metastatic Hormone-Sensitive Prostate Cancer

Vaishampayan, Ulka N.; Heilbrun, Lance K.; Monk, Paul; Tejwani, Sheela; Sonpavde, Guru; Hwang, Clara; Smith, Daryn; Jasti, Pallavi; Dobson, Kimberlee; Dickow, Brenda; Heath, Elisabeth I.; Semaan, Louie; Cher, Michael L.; Fontana, Joseph A.; Chinni, Sreenivasa R.

doi:10.1001/jamanetworkopen.2020.34633

Cited by 34 publications

(27 citation statements)

References 21 publications

(43 reference statements)

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“…The second-generation antiandrogens viz . enzalutamide, apalutamide and darolutamide, as well as inhibitors of androgen biosynthesis such as abiraterone acetate, improve upon this mechanism [ 8 ] . Changes in the function of AR signaling result in tumor suppression to tumor promotion, where the disease eventually progresses to the emergence of castration-resistant prostate cancer (CRPC) [ 9 ] .…”

Section: Introductionmentioning

confidence: 99%

Role of prostate cancer stem-like cells in the development of antiandrogen resistance

et al. 2022

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Androgen deprivation therapy (ADT) is the standard of care treatment for advance stage prostate cancer. Treatment with ADT develops resistance in multiple ways leading to the development of castration-resistant prostate cancer (CRPC). Present research establishes that prostate cancer stem-like cells (CSCs) play a central role in the development of treatment resistance followed by disease progression. Prostate CSCs are capable of self-renewal, differentiation, and regenerating tumor heterogeneity. The stemness properties in prostate CSCs arise due to various factors such as androgen receptor mutation and variants, epigenetic and genetic modifications leading to alteration in the tumor microenvironment, changes in ATP-binding cassette (ABC) transporters, and adaptations in molecular signaling pathways. ADT reprograms prostate tumor cellular machinery leading to the expression of various stem cell markers such as Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1), Prominin 1 (PROM1/CD133), Indian blood group (CD44), SRY-Box Transcription Factor 2 (Sox2), POU Class 5 Homeobox 1(POU5F1/Oct4), Nanog and ABC transporters. These markers indicate enhanced self-renewal and stemness stimulating CRPC evolution, metastatic colonization, and resistance to antiandrogens. In this review, we discuss the role of ADT in prostate CSCs differentiation and acquisition of CRPC, their isolation, identification and characterization, as well as the factors and pathways contributing to CSCs expansion and therapeutic opportunities.

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Section: Introductionmentioning

confidence: 99%

Role of prostate cancer stem-like cells in the development of antiandrogen resistance

et al. 2022

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“…Furthermore, an in‐depth analysis of TME composition and activity in AA patients, specifically those that received sipuleucel‐T, could open a myriad of opportunities for researching the biology behind survival advantage in this population. Recent dedicated studies focused on AA patients, such as a trial evaluating enzalutamide vs bicalutamide use in mCRPC, 136 are a promising start. However, representation of AA patients in prostate cancer and oncology clinical trials remains scarce and not reflective of the general population.…”

Section: Discussionmentioning

confidence: 99%

Immune mechanisms behind prostate cancer in men of African ancestry: A review

et al. 2022

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Background: Men of African ancestry (AA) with prostate cancer suffer from worse outcomes. However, a recent analysis of patients treated with the dendritic cell vaccine sipuleucel-T for prostate cancer suggested that AA patients could have improved outcomes relative to whites. Methods:We conducted a focused literature review of Medline-indexed articles and clinical trials listed on clinicaltrials.gov. Results:We identify several studies pointing to enrichment of inflammatory cellular infiltrates and cytokine signaling among AA patients with prostate cancer. We outline potential genomic and transcriptomic alterations that may contribute to immunogenicity. Last, we investigate differences in host immunity and vaccine responsiveness that may be enhanced in AA patients.Conclusions: AA patients with prostate cancer may be enriched for an immunogenic phenotype. Dedicated studies are needed to better understand the immune mechanisms that contribute to existing cancer disparities and test immune-based therapies in this population.

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“…As second-generation androgen receptor inhibitors, they have already been recommended by the latest EAU guidelines ( Cornford et al, 2021 ). Numerous studies have demonstrated that the second-generation androgen receptor inhibitor is associated with improved outcomes compared with bicalutamide in CRPC ( Penson et al, 2016 ; Naiki et al, 2021 ; Ueda et al, 2021 ; Vaishampayan et al, 2021 ). Therefore, the drug sensitivity of Abiraterone and Enzalutamide between high- and low-risk groups needs to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Gene Signature to Aid Treatment Decisions by Integrated Analysis of Mutated Genes Between Primary and Metastatic Prostate Cancer

Xiao

Chen

et al. 2022

Front. Genet.

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Prostate cancer is one of the most common malignancies in males. Despite the recent development of advanced diagnostic platforms and treatment, patients with metastatic disease still have a poor five-year survival rate. Cancer metastasis is correlated with the characteristics of the tumor microenvironment and is significantly associated with patient prognosis. In this study, we obtained mutated genes with significant differences between primary and metastatic prostate cancer from the COSMIC database. Unsupervised consensus clustering was used based on the 1,051 genes obtained, and two PCa clusters were identified, which exhibited different prognostic outcomes and immune characteristics. Next, we generated a scoring system and evaluated the prognostic value of riskscore and its potential to aid treatment decisions in clinical practice. The riskscore could be applied to predict patients’ response to immunotherapy and sensitivity to Docetaxel. In conclusion, this study performed an integrated analysis of mutated genes between primary and metastatic prostate cancer and provides a novel assessment scheme to precisely select treatment strategies.

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Clinical Efficacy of Enzalutamide vs Bicalutamide Combined With Androgen Deprivation Therapy in Men With Metastatic Hormone-Sensitive Prostate Cancer

Cited by 34 publications

References 21 publications

Role of prostate cancer stem-like cells in the development of antiandrogen resistance

Role of prostate cancer stem-like cells in the development of antiandrogen resistance

Immune mechanisms behind prostate cancer in men of African ancestry: A review

Identification of a Gene Signature to Aid Treatment Decisions by Integrated Analysis of Mutated Genes Between Primary and Metastatic Prostate Cancer

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