Androgen Receptor, Resistensi Terapi, dan Pendekatan Terapeutik Baru pada Kanker Prostat
DOI:
https://doi.org/10.37287/jppp.v7i6.1064Keywords:
antagonis androgen, kanker prostat resisten kastrasi, kimera penargetan proteolisis, resistensi obat androgen, reseptor androgen, terapi target molekulerAbstract
Androgen receptor (AR) merupakan penggerak utama perkembangan kanker prostat dan tetap aktif meskipun kadar testosteron telah mencapai kondisi kastrasi. Resistensi terapi muncul melalui amplifikasi AR, mutasi ligand-binding domain (LBD), varian splice seperti AR-V7, bypass pathways (misalnya glucocorticoid receptor), serta aktivasi jalur non-AR seperti PI3K/AKT dan NF-κB. Tinjauan sistematis ini menganalisis mekanisme resistensi berbasis AR, peran jalur non-AR, serta efektivitas pendekatan terapeutik baru pada castration-resistant prostate cancer (CRPC). Systematic review dilakukan sesuai PRISMA 2020. PICO digunakan untuk merumuskan pertanyaan riset. Pencarian dilakukan pada PubMed, Scopus, Web of Science, dan Embase menggunakan kata kunci seperti “prostate cancer”, “castration-resistant prostate cancer”, “androgen receptor”, “AR-V7”, “antiandrogen resistance”, dan “novel AR-targeted therapy” dengan rentang publikasi 2015–2025. Screening dilakukan oleh dua reviewer independen. Kualitas studi dianalisis menggunakan RoB-2 dan Newcastle–Ottawa Scale. Dari 1.972 artikel yang teridentifikasi pada tahap awal, sebanyak 33 studi memenuhi kriteria inklusi dan disertakan dalam sintesis akhir. Lima tema utama ditemukan: (1) reaktivasi AR melalui amplifikasi, mutasi, dan AR-V7; (2) aktivasi jalur non-AR; (3) resistensi terhadap antiandrogen generasi baru; (4) terapi inovatif seperti PROTACs, AR-V7 degraders, N-terminal domain inhibitors, dan RNA interference; (5) pendekatan drug repurposing & strategi re-sensitisasi seperti Bipolar Androgen Therapy (BAT). Resistensi CRPC didorong oleh interaksi kompleks antara perubahan AR, jalur kompensasi non-AR, dan adaptasi epigenetik. Terapi multimodal berbasis biomarker menjadi arah masa depan pengelolaan CRPC.
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