Tissue-specific cancer stem/progenitor cells: Therapeutic implications

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.

Key Words: 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.