Biomarkers for Predicting Abiraterone Treatment Outcome and Selecting Alternative Therapies in Castration-Resistant Prostate Cancer.

Autor: Qin S; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Gao H; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Kim W; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.; Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA., Zhang H; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Gu Y; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Kalari KR; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Sinnwell JP; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Scholz JA; Department of Comparative Medicine, Mayo Clinic, Rochester, Minnesota, USA., Xie F; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Yin P; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.; Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA., Yu J; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Qin B; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Zhuang Y; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Wei L; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Tan W; Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida, USA., Bryce AH; Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, Arizona, USA., Weinshilboum RM; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., Wang L; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2022 Jun; Vol. 111 (6), pp. 1296-1306. Date of Electronic Publication: 2022 Apr 12.
DOI: 10.1002/cpt.2582
Abstrakt: Approximately one-third of patients with metastatic castration-resistant prostate cancer (CRPC) exhibited primary abiraterone resistance. To identify alternative treatment for abiraterone nonresponders, we performed drug discovery analyses using the L1000 database using differentially expressed genes identified in tumor biopsies and patient-derived xenograft (PDX) tumors between abiraterone responders and nonresponders enrolled in PROMOTE trial. This approach identified 3 drugs, including topoisomerase II (TOP2) inhibitor mitoxantrone, CDK4/6 inhibitor palbociclib, and pan-CDK inhibitor PHA-793887. These drugs significantly suppressed the growth of abiraterone-resistant cell lines and PDX models. Moreover, we identified 11 genes targeted by all 3 drugs that were associated with worse outcomes in both the PROMOTE and Stand Up To Cancer cohorts. This 11-gene panel might also function as biomarkers to select the 3 alternative therapies for this subgroup of patients with CRPC, warranting further clinical investigation.
(© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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