Colorectal Cancer Stem Cells and Targeted Agents

Abstract

Since their discovery, cancer stem cells have become a hot topic in cancer therapy research. These cells possess stem cell-like self-renewal and differentiation capacities and are important factors that dominate cancer metastasis, therapy-resistance and recurrence. Worse, their inherent characteristics make them difficult to eliminate. Colorectal cancer is the third-most common cancer and the second leading cause of cancer death worldwide. Targeting colorectal cancer stem cells (CR-CSCs) can inhibit colorectal cancer metastasis, enhance therapeutic efficacy and reduce recurrence. Here, we introduced the origin, biomarker proteins, identification, cultivation and research techniques of CR-CSCs, and we summarized the signaling pathways that regulate the stemness of CR-CSCs, such as Wnt, JAK/STAT3, Notch and Hh signaling pathway. In addition to these, we also reviewed recent anti-CR-CSC drugs targeting signaling pathways, biomarkers and other regulators. These will help researchers gain insight into the current agents targeting to CR-CSCs, explore new cancer drugs and propose potential therapies.

Integration of single-cell sequencing and bulk RNA-seq to identify and develop a prognostic signature related to colorectal cancer stem cells

“…The increasing incidence of CRC can be linked to diverse factors such as economic development, lifestyle choices, environmental changes, and genetic predisposition 87 . Within this context, CRCSCs represent a subset of cancer cells characterized by robust proliferation and limited differentiation abilities 88 . These cells propel tumor progression, support immune escape, and foster drug resistance through complex interactions and signaling pathways within the tumor microenvironment (TME), thereby influencing CRC's vulnerability to recurrence 89 .…”

The Impact of Cancer Stem Cells in Colorectal Cancer

“…These strategies utilize viruses engineered to selectively annihilate tumor cells while sparing healthy tissue, sparking targeted immune responses against CSCs. Viruses tailored with a CD133-targeting sequence, for instance, have successfully purged CD133+ CSCs, demonstrating a promising reduction in tumor proliferation in xenograft studies [108,109].…”

“…Similarly, targeting the Hh and Notch pathways, pivotal for tissue development and cellular differentiation, respectively, with specific inhibitors modifies CSC behavior and therapy responsiveness. In the same vein, interventions against the PI3K/Akt/mTOR and JAK/STAT3 pathways, linked to cancer progression and metastasis, are pursued to dampen CSC proliferation and stemness [64,108,109].…”

“…Inhibiting pathways like GLUT1 or the KRAS-JNK axis presents a viable strategy to diminish CSC stemness and resistance, charting a new course for combatting CRC. Emerging therapeutic strategies, including clinical trials investigating the synergistic use of metformin and CSC-targeted dendritic cell vaccines, illuminate the potential to develop cutting-edge immunotherapies [108,109].…”