Mechanisms of chemoresistance in cancer stem cells

TLDR

Chemotherapy is a standard treatment for many cancers, yet recurrence and death often occur because cancer stem cells (CSCs) drive resistance; various mechanisms of chemoresistance in CSCs have been identified. This review describes CSC chemoresistance mechanisms—including ABC transporters, ALDH activity, BCL2-related pathways, enhanced DNA damage response, and key signaling pathways—and evaluates studies proposing ways to overcome this resistance. The authors analyze these mechanisms by examining ABC transporter expression, ALDH activity, BCL2-related pathways, DNA damage response, and key signaling pathways, and assess potential therapeutic strategies. By elucidating how CSCs evade chemotherapy, more informed approaches to treatment can be developed, potentially improving clinical outcomes for cancer patients.

Abstract

Chemotherapy is one of the standard methods of treatment in many cancers. While chemotherapy is often capable of inducing cell death in tumors and reducing the tumor bulk, many cancer patients experience recurrence and ultimately death because of treatment failure. In recent years, cancer stem cells (CSCs) have gained intense interest as key tumor-initiating cells that may also play an integral role in recurrence following chemotherapy. As such, a number of mechanisms of chemoresistance have been identified in CSCs. In this review, we describe a number of these mechanisms of chemoresistance including ABC transporter expression, aldehyde dehydrogenase (ALDH) activity, B-cell lymphoma-2 (BCL2) related chemoresistance, enhanced DNA damage response and activation of key signaling pathways. Furthermore, we evaluate studies that demonstrate potential methods for overcoming chemoresistance and treating chemoresistant cancers that are driven by CSCs. By understanding how tumor-initiating cells such as CSCs escape chemotherapy, more informed approaches to treating cancer will develop and may improve clinical outcomes for cancer patients.