Patient-Derived Conditionally Reprogrammed Cells in Prostate Cancer Research

患者来源的条件性重编程细胞在前列腺癌研究中的应用

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作者:Abdalla Elbialy, Deepthi Kappala, Dhruv Desai, Peng Wang, Ahmed Fadiel, Shang-Jui Wang, Mina S Makary, Scott Lenobel, Akshay Sood, Michael Gong, Shawn Dason, Ahmad Shabsigh, Steven Clinton, Anil V Parwani, Nagireddy Putluri, Gennady Shvets, Jenny Li, Xuefeng Liu0

Abstract

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications of the conditional reprogramming (CR) cell culture approach, showcasing its capability to rapidly and effectively cultivate patient-derived normal and tumor cells. The CR strategy facilitates the acquisition of stem cell properties by primary cells, precisely recapitulating the human pathophysiology of PCa. This nuanced understanding enables the identification of novel therapeutics. Specifically, our discussion encompasses the utility of CR cells in elucidating PCa initiation and progression, unraveling the molecular pathogenesis of metastatic PCa, addressing health disparities, and advancing personalized medicine. Coupled with the tumor organoid approach and patient-derived xenografts (PDXs), CR cells present a promising avenue for comprehending cancer biology, exploring new treatment modalities, and advancing precision medicine in the context of PCa. These approaches have been used for two NCI initiatives (PDMR: patient-derived model repositories; HCMI: human cancer models initiatives).

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