Targeting the Mechanisms of Resistance to Chemotherapy and Radiotherapy with the Cancer Stem Cell Hypothesis

TLDR

Cancer remains the second leading cause of death in the U.S., and its poor cure rates are driven by recurrence and metastasis linked to cancer stem cells that are resistant to chemotherapy and radiation, underscoring the need to understand their resistance mechanisms. The study aims to update evidence on CSCs’ role in cancer progression, summarize resistance mechanisms, and review promising drugs targeting CSCs to improve treatment outcomes. It reviews mechanisms of CSC resistance to chemo‑ and radiotherapy and evaluates preclinical/clinical agents designed to target these mechanisms.

Abstract

Despite advances in treatment, cancer remains the 2nd most common cause of death in the United States. Poor cure rates may result from the ability of cancer to recur and spread after initial therapies have seemingly eliminated detectable signs of disease. A growing body of evidence supports a role for cancer stem cells (CSCs) in tumor regrowth and spread after initial treatment. Thus, targeting CSCs in combination with traditional induction therapies may improve treatment outcomes and survival rates. Unfortunately, CSCs tend to be resistant to chemo- and radiation therapy, and a better understanding of the mechanisms underlying CSC resistance to treatment is necessary. This paper provides an update on evidence that supports a fundamental role for CSCs in cancer progression, summarizes potential mechanisms of CSC resistance to treatment, and discusses classes of drugs currently in preclinical or clinical testing that show promise at targeting CSCs.