Drug resistance in cancer therapy: the Pandora's Box of cancer stem cells

Abstract

Drug resistance is the main culprit of failure in cancer therapy that may lead to cancer relapse. This resistance mostly originates from rare, but impactful presence of cancer stem cells (CSCs). Ability to self-renewal and differentiation into heterogeneous cancer cells, and harboring morphologically and phenotypically distinct cells are prominent features of CSCs. Also, CSCs substantially contribute to metastatic dissemination. They possess several mechanisms that help them to survive even after exposure to chemotherapy drugs. Although chemotherapy is able to destroy the bulk of tumor cells, CSCs are left almost intact, and make tumor entity resistant to treatment. Eradication of a tumor mass needs complete removal of tumor cells as well as CSCs. Therefore, it is important to elucidate key features underlying drug resistance raised by CSCs in order to apply effective treatment strategies. However, the challenging point that threatens safety and specificity of chemotherapy is the common characteristics between CSCs and normal peers such as signaling pathways and markers. In the present study, we tried to present a comprehensive appraisal on CSCs, mechanisms of their drug resistance, and recent therapeutic methods targeting this type of noxious cells.

RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer

“…A reduction in RUNX1 transcriptional activity significantly improves the efficacy of Px and Enza in forced suspension culture (Figure 6). Under these conditions we had to use higher doses of all the drugs, including RUNX1 inhibitor, to achieve a reduction in cell viability rate similar to the one obtained in standard adherent cultures (Figure 6), validating the already known concept that CSC populations are more resistant to treatment [42]. S3.…”

New anti-cancer explorations based on metal ions

“…At the same time, external energy can realize the controlled release of nano-drugs based on metal ions and mediate synergistic treatment. Besides, it has been confirmed that most tumor cells are not resistant to metal ions [ 282 ], which enables metal ions to apply to multi-course treatment. Further, the metal ion-mediated cancer diagnosis is conducive to monitoring and controlling the therapeutic process, improving treatment efficiency.…”

AQP5 complements LGR5 to determine the fates of gastric cancer stem cells through regulating ULK1 ubiquitination

“…Moreover, these CSCs acquire multidrug resistance, thus protecting themselves from most traditional chemotherapeutic agents. As a result, this small subpopulation of persistent cells forms more aggressive and chemoresistant tumors, resulting in the failure of cancer therapy [ 9 ]. Thus, identifying and targeting these rare cancer cells are believed to be important for understanding the etiology of cancer and developing a novel therapeutic strategy for cancer therapy [ 10 ].…”