Pengaruh Variasi Gen CYP2D6 Terhadap Terapi Tamoxifen Pada Pasien Kanker Payudara di Kawasan Asia
DOI:
https://doi.org/10.46815/jk.v13i1.251Kata Kunci:
CYP2D6, Kanker Payudara, Variasi Genetik, Tamoxifen Personalized MedicineAbstrak
Kanker payudara merupakan salah satu kanker yang paling banyak diderita oleh masyarakat, terutama oleh wanita. Tamoxifen sering digunakan sebagai terapi lini pertama untuk kanker payudara serta mengurangi risiko kekambuhan pada kanker payudara ER+. Namun, respon yang dihasilkan dari pengobatan bervariasi, perbedaan respon ini terjadi karena adanya variabilitas genetik hasil polimorfisme pada DNA yang mengkode enzim metabolisme obat salah satunya yaitu gen CYP2D6. Tujuan dari review jurnal ini adalah untuk mengevaluasi dampak dari varian gen CYP2D6 terhadap efektivitas tamoxifen pada pengobatan kanker payudara. Literatur review dilakukan melalui situs PubMed, Google Scholar, dan BMC Cancer dengan menggunakan kata kunci yang relevan dan artikel tidak lebih dari 10 tahun terakhir (2014-2024) dengan kriteria inklusi dan ekslusi. Berdasarkan hasil review artikel dari berbagai jurnal penelitian ditemukan bahwa di kawasan Asia, variasi gen CYP2D6 alel *10 ditemukan paling sering, yang menghasilkan Intermediate metabolism (IM) pada terapi tamoxifen. Pasien dengan metabolisme IM cenderung memiliki respon terapeutik yang kurang optimal dan memerlukan penyesuian dosis tamoxifen. Sebaliknya, pasien dengan metabolisme normal (NM/EM) cenderung memiliki respon terapeutik yang lebih baik. Variabilitas genetik dalam gen CYP2D6 memengaruhi aktivitas enzim CYP2D6 yang berfungsi untuk mengkonversi tamoxifen menjadi bentuk aktifnya, yaitu endoxifen. Beberapa individu dapat memiliki aktivitas enzim yang rendah (Poor metabolizer), sedang (Intermediate metabolizer), normal (Extensive metabolizer), bahkan tinggi (Ultra-rapid metabolizer). Oleh karena itu, penyesuaian terapi tamoxifen berdasarkan informasi genetik pasien menjadi penting untuk mencapai pengobatan yang optimal, khususnya di kawasan Asia dimana variasi gen CYP2D6 alel *10 paling umum ditemukan dan menghasilkan metabolisme IM.
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