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Review
. 2024 Jun 8;13(12):1005.
doi: 10.3390/cells13121005.

Patient-Derived Conditionally Reprogrammed Cells in Prostate Cancer Research

Abdalla Elbialy  1   2 , Deepthi Kappala  1 , Dhruv Desai  1 , Peng Wang  1 , Ahmed Fadiel  2 , Shang-Jui Wang  1   3 , Mina S Makary  1   4 , Scott Lenobel  1   5 , Akshay Sood  1   6 , Michael Gong  1   6 , Shawn Dason  1   6 , Ahmad Shabsigh  1   6 , Steven Clinton  1 , Anil V Parwani  1   7 , Nagireddy Putluri  8 , Gennady Shvets  9 , Jenny Li  1   7 , Xuefeng Liu  1   10
Affiliations
Review

Patient-Derived Conditionally Reprogrammed Cells in Prostate Cancer Research

Abdalla Elbialy et al. Cells. .

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).

Keywords: CR; PCa; patient-derived cells.

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Conflict of interest statement

Several patents for CR technology have been awarded to Georgetown University by the US Patent Office. The license for this technology has been given to a Maryland-based start-up company for commercialization. The inventor, X.L., and Georgetown University receive potential royalties and payments from the company. CR media and CR cells have been distributed by Propagenix, StemCell Technologies, Fisher Scientific, ATCC, etc. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1
Figure 1
Application of CR technology to study PCa.
Figure 2
Figure 2
Understanding of the health disparity in study of PCa. The diagram delineates the multifaceted contributors to health disparities in PCa, focusing on ethnic groups such as African American, European American, Asian American, and Hispanic and Latin American. It features critical research domains like marker discovery, pathways studies, and genomics studies, which are pivotal in both understanding and influencing these disparities. Beyond genetic predispositions, the diagram acknowledges that disparities are further exacerbated by social-economic, cultural, educational, and environmental factors. Additionally, it recognizes the inherent diversity of PCa presentations, with conditions like BPH, CRPC, and NEPC being indicative of the disease’s variable impact on health outcomes.
Figure 3
Figure 3
Personalized marker identification for precision medicine for the PCa. This figure illustrates the spectrum of PCa conditions—including BPH (benign prostatic hyperplasia), CRPC (castration-resistant PCa), and NEPC (neuroendocrine PCa)—and highlights the role of health disparities in the variation of disease states from one individual to another. It underscores the importance of personalized medicine research in identifying unique markers for each patient, with the goal of providing tailored treatments. The central box outlines the components of this research approach: (1) markers, (2) pathways, (3) omics (encompassing genomics, proteomics, and other related fields), (4) rapid models, (5) drug Screening, (6) animal Study, and (7) monitoring.
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