The Evolving Role of Enzalutamide on the Treatment of Prostate Cancer

Abstract

The field of prostate cancer has witnessed incredible progress in the last decade, owing to the approval of multiple survival-prolonging treatments for metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide is a nonsteroidal androgen receptor inhibitor that targets multiple steps in the androgen receptor signaling axis. It has been approved for the treatment of mCRPC both in the postdocetaxel and in the chemotherapy-naive settings. We summarize the milestones in the development of enzalutamide in patients with prostate cancer. Special focus is placed on the results of the STRIVE Phase II clinical trial comparing head to head enzalutamide and bicalutamide in patients with nonmetastatic and mCRPC who have failed androgen deprivation and in other ongoing trials in the same setting and in earlier disease phases.

Efficient Everolimus Treatment for Metastatic Castration Resistant Prostate Cancer with AKT1 Mutation: A Case Report

“… 15 According to previous studies, 16 we deduced that bicalutamide resistance was attributable to AR-Vs. Moreover, various clinical studies found that abiraterone and enzalutamide had no satisfactory long-term therapeutic effect in the mCRPC patients with AR-Vs. 17 These findings could explain the high-level PSA of the patient, especially for the late stage of treatment. It was also notable that the PI3K-AKT-mTOR signaling pathway was altered in almost 100% of advanced-stage PCas.…”

Therapeutic Strategies to Target the Androgen Receptor

“…A phase II study with apalutamide demonstrated durable activity in non-mCRPC, pre- and post-abiraterone acetate, and prednisone mCRPC arms with a median PSA level at week 12 decreasing to 85%, 88%, and 22%, respectively . Apalutamide in phase III trials of CRPC achieved median metastasis-free survival of 40 months compared with 16 months for the placebo . A common side effect of apalutamide is skin rash, which can be attributed to the cyano pyrimidine moiety, which is capable of attaching to cysteine residues in proteins through a reversible covalent bond …”

“…187 Apalutamide in phase III trials of CRPC achieved median metastasis-free survival of 40 months compared with 16 months for the placebo. 188 A common side effect of apalutamide is skin rash, which can be attributed to the cyano pyrimidine moiety, which is capable of attaching to cysteine residues in proteins through a reversible covalent bond. 189 JNJ-63576253 ( 110) is a clinical stage second-generation AR antagonist capable of overcoming a subset of enzalutamide and apalutamide resistance.…”

Review on Potential Targeted Therapy for Triple Negative Breast Cancer

“…Another phase II trial, evaluating new anti androgen receptor which is enzalutamide. Enzalutamide is antiandrogen that inhibit androgen receptor signalling pathway which will prevent transcription of androgen responsives gene (Nadal & Bellmunt, 2016). In this study 118 patients were received enzalutamide 160mg once per day until disease progression.…”