Current uses and resistance mechanisms of enzalutamide in prostate cancer treatment
2
Issued Date
2024-01-01
Resource Type
ISSN
14737140
eISSN
17448328
Scopus ID
2-s2.0-85204599478
Pubmed ID
39275993
Journal Title
Expert Review of Anticancer Therapy
Rights Holder(s)
SCOPUS
Bibliographic Citation
Expert Review of Anticancer Therapy (2024)
Suggested Citation
Miller C.D., Likasitwatanakul P., Toye E., Hwang J.H., Antonarakis E.S. Current uses and resistance mechanisms of enzalutamide in prostate cancer treatment. Expert Review of Anticancer Therapy (2024). doi:10.1080/14737140.2024.2405103 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/101428
Title
Current uses and resistance mechanisms of enzalutamide in prostate cancer treatment
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
Introduction: Prostate cancer continues to be a major cause of morbidity and mortality for men worldwide. Enzalutamide, a second-generation non-steroidal antiandrogen that blocks androgen receptor (AR) transcriptional activity, is a treatment for biochemically recurrent, metastatic, castration-sensitive, and castration-resistant tumors. Unfortunately, most patients ultimately develop resistance to enzalutamide, making long-term treatment with this agent challenging. Areas covered: We performed a literature search of PubMed without date restrictions to investigate the literature surrounding enzalutamide and discuss the current uses of enzalutamide, proposed mechanisms driving resistance, and summarize current efforts to mitigate this resistance. Expert opinion: Enzalutamide is an effective prostate cancer therapy that is currently used in biochemically recurrent and metastatic disease and for both castration-sensitive and castration-resistant tumors. Unfortunately, resistance to enzalutamide occurs in each of these scenarios. In the clinical setting, enzalutamide-resistant tumors are either AR-driven or AR-indifferent. AR-dependent resistance mechanisms include genomic or epigenomic events that result in enhanced AR signaling. Tumors that do not require AR signaling instead may depend on alternative oncogenic pathways. There are numerous strategies to mitigate enzalutamide resistance, including concurrent use of PARP inhibitors or immune therapies. Additional work is required to uncover novel approaches to treat patients in the enzalutamide-resistant setting.