Precision Targeting in Metastatic Castration-Resistant Prostate Cancer: Advancements in Personalized Therapeutics

Authors

  • ALI HASSAN SALIM KIDIYA Intern, Dr. B. R Ambedkar Medical college and hospital
  • Arshiya ummey Medical Student, University Of Perpetual Help System DALTA, Philippines
  • Naga Sai Gouthami Gurujala Medical graduate, Nri Medical College, India
  • Srijamya MD. ASMC, Lakhimpur Kheri, Uttar Pradesh, India.

Keywords:

Mevrometostat, EZH2 gene, Enzalutamide, Synergism, Hormone resistance

Abstract

Background: 

Castration-resistant prostate cancer continues to be an incurable and aggressive

condition. Enzalutamide; an antiandrogen, shows better radiographic progression-free

survival and overall survival in men with metastatic castration-resistant prostate cancer

and reduces risk of progression or death by 68%. Gene EZH2 activity in prostate cancer

is linked to promote progression and resistance to hormone therapies. Mevrometostat

targets this EZH2 gene. Therefore, this combination can be beneficial to maximise the

results.

 

Objective:

To explore the safety and efficacy of mevrometostat (PF-06821497), an LSD1 inhibitor,

combined with enzalutamide in patients with metastatic castration-resistant prostate

cancer who have progressed after prior androgen receptors–targeted therapy.

 

Methodology:

A randomized open label, phase 3 trial was conducted in patients with metastatic castration resistant prostate cancer. The primary aim of the study is to evaluate the Radiographic Progression free Survival. The secondary targets include overall survival, time to pain progression, pharmacokinetics, ct DNA and patient-reported outcomes.

 

Results:

In the randomized dose-expansion cohorts, 81 patients were assessed (41 received mevrometostat combined with enzalutamide, while 40 were given enzalutamide alone). The baseline characteristics were similar (median age around 70 years; ECOG performance status of 0-1, many had prior abiraterone treatment). The median radiographic progression-free survival (rPFS) was 14.3 months (95% CI, 7.5-Non Estimable) for the combination of mevrometostat and enzalutamide, compared to 6.2 months (95% CI, 4.1-13.9) for enzalutamide alone (hazard ratio 0.51; 90% CI, 0.28-0.95), suggesting a roughly 49% reduction in the radiological progression and risk of death with an average follow-up of about 9.6 months.

 

Conclusion:

Dual EZH2 and AR inhibition in metastatic castration prostate cancer with mevrometostat and enzalutamide shows synergism in overcoming resistance and improving therapeutic outcomes through activating the immune pathways.

References

1. Ligon, J.A., Anand, S., Singh, S. et al. Genomic landscape and precision therapy in prostate cancer: current status and future directions. npj Precis. Onc. 10, 172 (2026). https://doi.org/10.1038/s41698-026-01368-3

2. Ferretti S, Mercinelli C, Marandino L, Litterio G, Marchioni M, Schips L. Metastatic Castration-Resistant Prostate Cancer: Insights on Current Therapy and Promising Experimental Drugs. Res Rep Urol. 2023 Jun 26;15:243-259. doi: 10.2147/RRU.S385257. PMID: 37396015; PMCID: PMC10312338.

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Published

2026-08-19

How to Cite

KIDIYA, A. H. S., Arshiya ummey, Naga Sai Gouthami Gurujala, & Srijamya. (2026). Precision Targeting in Metastatic Castration-Resistant Prostate Cancer: Advancements in Personalized Therapeutics. International Journal of Medical Students. Retrieved from https://ijms.pitt.edu/IJMS/article/view/4866

Issue

Forthcoming

Section

Abstracts of the WCMSR

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Copyright (c) 2026 ALI HASSAN SALIM KIDIYA, Arshiya ummey, Naga Sai Gouthami Gurujala, Srijamya

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