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World J Stem Cells. May 26, 2023; 15(5): 323-341
Published online May 26, 2023. doi: 10.4252/wjsc.v15.i5.323
Tissue-specific cancer stem/progenitor cells: Therapeutic implications
Amani Yehya, Joe Youssef, Sana Hachem, Jana Ismael, Wassim Abou-Kheir
Amani Yehya, Joe Youssef, Sana Hachem, Jana Ismael, Wassim Abou-Kheir, Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107-2020, Lebanon
Author contributions: Yehya A contributed conceptualization, investigation, methodology, visualization, and validation, wrote the original draft, and reviewed and edited the manuscript; Youssef J, Hachem S, and Ismael J contributed investigation, methodology, and validation, wrote the original draft, and reviewed and edited the manuscript; Abou-Kheir W contributed conceptualization, project administration, supervision, validation, and visualization, reviewed and edited the manuscript, and gave final approval; All authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wassim Abou-Kheir, MSc, PhD, Associate Professor, Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Bliss Street, Hamra, Beirut 1107-2020, Lebanon. wa12@aub.edu.lb
Received: December 28, 2022
Peer-review started: December 28, 2022
First decision: January 31, 2023
Revised: February 14, 2023
Accepted: April 12, 2023
Article in press: April 12, 2023
Published online: May 26, 2023
Abstract

Surgical resection, chemotherapy, and radiation are the standard therapeutic modalities for treating cancer. These approaches are intended to target the more mature and rapidly dividing cancer cells. However, they spare the relatively quiescent and intrinsically resistant cancer stem cells (CSCs) subpopulation residing within the tumor tissue. Thus, a temporary eradication is achieved and the tumor bulk tends to revert supported by CSCs' resistant features. Based on their unique expression profile, the identification, isolation, and selective targeting of CSCs hold great promise for challenging treatment failure and reducing the risk of cancer recurrence. Yet, targeting CSCs is limited mainly by the irrelevance of the utilized cancer models. A new era of targeted and personalized anti-cancer therapies has been developed with cancer patient-derived organoids (PDOs) as a tool for establishing pre-clinical tumor models. Herein, we discuss the updated and presently available tissue-specific CSC markers in five highly occurring solid tumors. Additionally, we highlight the advantage and relevance of the three-dimensional PDOs culture model as a platform for modeling cancer, evaluating the efficacy of CSC-based therapeutics, and predicting drug response in cancer patients.

Keywords: Cancer stem cells, Therapy resistance, Tissue-specific cancer stem cell markers, Patient-derived organoids, Pre-clinical cancer models

Core Tip: Therapeutic approaches targeting cancer stem cell (CSC) markers hold great promise toward developing effective anti-cancer treatment. Tissue-specific CSCs (TSCSCs) possess unique expression profile that allows for their identification, isolation, and targeting. TSCSCs, isolated from patient tumor tissues, were shown to form organ analogs or patient-derived organoids (PDOs) under specific culturing conditions in vitro. These models simulate the original tumor characteristics in a three-dimensional culture dish. As such, PDOs have the potential to be used in patient-specific in vitro drug clinical trials and proof-of-concept studies on CSC-targeted therapies.