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Stem Cells as Target for Prostate cancer Therapy: Opportunities and Challenges

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Abstract

Cancer stem cells (CSCs) and cells in a cancer stem cell-like (CSCL) state have proven to be responsible for tumor initiation, growth, and relapse in Prostate Cancer (PCa) and other cancers; therefore, new strategies are being developed to target such cellular populations. TLR3 activation-based immunotherapy using Polyinosinic:Polycytidylic acid (PIC) has been proposed to be used as a concomitant strategy to first-line treatment. This strategy is based on the induction of apoptosis and an inflammatory response in tumor cells. In combination with retinoids like 9cRA, this treatment can induce CSCs differentiation and apoptosis. A limitation in the use of this combination is the common decreased expression of TLR3 and its main positive regulator p53. observed in many patients suffering of different cancer types such as PCa. Importantly, human exposure to certain toxicants, such as iAs, not only has proven to enrich CSCs population in an in vitro model of human epithelial prostate cells, but additionally, it can also lead to a decreased p53, TLR3 and RA receptor (RARβ), expression/activation and thus hinder this treatment efficacy. Therefore, here we point out the relevance of evaluating the TLR3 and P53 status in PCa patients before starting an immunotherapy based on the use of PIC +9cRA to determine whether they will be responsive to treatment. Additionally, the use of strategies to overcome the lower TLR3, RARβ or p53 expression in PCa patients, like the inclusion of drugs that increase p53 expression, is encouraged, to potentiate the use of PIC+RA based immunotherapy in these patients.

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Acknowledgements

Authors acknowledge the contribution of Jesús Gómez Montalvo, member of the RNA Metabolism and Extracellular Vesicles Consortium, National Institute of Genomic Medicine, (INMEGEN), Mexico City, for the rigorous analysis done from various databases to determine the expression of TLR3 and RARβ in clinical samples from patients with PCa.

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  1. Laboratorio de Inmunotoxicología, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Manuel Nava 6, Zona universitaria, 78240, San Luis Potosi, SLP, México

    Claudia Escudero-Lourdes & Ildemar Alvarado-Morales

  2. Mechanistic Toxicology Branch, DNTP, National Institute of Environmental Health Sciences, NIEHS, Durham, NC, 27709, USA

    Erik J. Tokar

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Dr. Claudia Escudero-Lourdes, identified the opportunity to make this review and set up the corresponding structure and specific objectives of the manuscript. She conducted the analysis and final writing of most part of the manuscript, designed the figures and prepared the revised version of it and the answer to the reviewers’ comments.

Dr. Ildemar Alvarado-Morales, under the supervision of the corresponding author, worked in the acquisition and extraction of information from literature, manage the references database, and shaped the final version of the images.

Dr. Erick Tokar, discussed the scientific and conceptual framework of the article and provided substantial contributions in stylistic/grammatical issues.

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Correspondence to Claudia Escudero-Lourdes.

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Escudero-Lourdes, C., Alvarado-Morales, I. & Tokar, E.J. Stem Cells as Target for Prostate cancer Therapy: Opportunities and Challenges. Stem Cell Rev and Rep 18, 2833–2851 (2022). https://doi.org/10.1007/s12015-022-10437-6

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