Circulating Tumor Cell–Based Molecular Classifier for Predicting Resistance to Abiraterone and Enzalutamide in Metastatic Castration-Resistant Prostate Cancer
| Autor: | Yugang Wang, James Henderson, Udit Singhal, Ganesh S. Palapattu, Alexander Zaslavsky, Zachery R. Reichert, Jae Seung Chung, Daniel E. Spratt, Yuanyuan Qiao, Russell S. Taichman, Daniel H. Hovelson, Todd M. Morgan, Scott A. Tomlins |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research LHRH luteinizing hormone-releasing hormone Kaplan-Meier Estimate CTC circulating tumor cell Prostate cancer chemistry.chemical_compound ARSI androgen receptor signaling inhibitors AUC area under the curve 0302 clinical medicine Circulating tumor cell Prostate Antineoplastic Combined Chemotherapy Protocols Medicine Neoplasm Metastasis Aged 80 and over Area under the curve Middle Aged Neoplastic Cells Circulating Prognosis 3. Good health Prostatic Neoplasms Castration-Resistant medicine.anatomical_structure Treatment Outcome EpCAM epithelial cell adhesion molecule 030220 oncology & carcinogenesis Benzamides Androstenes IRB institutional review board medicine.medical_specialty Original article EMT epithelial mesenchymal transition 03 medical and health sciences Internal medicine Nitriles Phenylthiohydantoin Biomarkers Tumor Enzalutamide Humans mCRPC metastatic castrate-resistant prostate cancer IQR interquartile range Aged Neoplasm Staging Proportional Hazards Models business.industry Gene Expression Profiling TSPAN8 Computational Biology medicine.disease HR hazard ratio Gene expression profiling Androgen receptor 030104 developmental biology chemistry Drug Resistance Neoplasm PFS progression free survival Neoplasm Grading business |
| Zdroj: | Neoplasia (New York, N.Y.) |
| ISSN: | 1476-5586 1522-8002 |
| Popis: | While circulating tumor cell (CTC)–based detection of AR-V7 has been demonstrated to predict patient response to second-generation androgen receptor therapies, the rarity of AR-V7 expression in metastatic castrate-resistant prostate cancer (mCRPC) suggests that other drivers of resistance exist. We sought to use a multiplex gene expression platform to interrogate CTCs and identify potential markers of resistance to abiraterone and enzalutamide. 37 patients with mCRPC initiating treatment with enzalutamide (n = 16) or abiraterone (n = 21) were prospectively enrolled for CTC collection and gene expression analysis using a panel of 89 prostate cancer–related genes. Gene expression from CTCs was correlated with PSA response and radioclinical progression-free survival (PFS) using Kaplan-Meier and Cox regression analyses. Twenty patients (54%) had detectable CTCs. At a median follow-up of 11.3 months, increased expression of the following genes was significantly associated with shorter PSA PFS and radioclinical PFS: AR, AR-V7, PSA, PSCA, TSPAN8, NKX3.1, and WNT5B. Additionally, high SPINK1 expression was associated with increased PFS. A predictive model including all eight genes gave an area under the curve (AUC) of 0.84 for PSA PFS and 0.86 for radioclinical PFS. In comparison, the AR-V7 only model resulted in AUC values of 0.65 and 0.64.These data demonstrate that clinically relevant information regarding gene expression can be obtained from whole blood using a CTC-based approach. Multigene classifiers in this setting may allow for the development of noninvasive predictive biomarkers to guide clinical management. |
| Databáze: | OpenAIRE |
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