Cancer Stem Cells (CSCs) in Drug Resistance and their Therapeutic Implications in Cancer Treatment

Abstract

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are suggested to be responsible for drug resistance and cancer relapse due in part to their ability to self-renew themselves and differentiate into heterogeneous lineages of cancer cells. Thus, it is important to understand the characteristics and mechanisms by which CSCs display resistance to therapeutic agents. In this review, we highlight the key features and mechanisms that regulate CSC function in drug resistance as well as recent breakthroughs of therapeutic approaches for targeting CSCs. This promises new insights of CSCs in drug resistance and provides better therapeutic rationales to accompany novel anticancer therapeutics.

Figure 1

The origin of CSCs and combinational therapy of CSC targeting and bulk tumor ablation. CSCs could possibly have originated from either stem cells with mutation/oncogenic transformation, progenitors that have undergone mutation, or from differentiated cells or cancer cells that obtained stem-like properties by dedifferentiation. Thus, because of the plasticity of CSCs, it is suggested that combinational therapy of CSC targeting and bulk tumor ablation may have better therapeutic effects to improve the clinical outcomes of cancer patients.

Figure 2

Key signaling pathways and modifications of CSCs contributing to the resistance against chemotherapeutics. In order to survive during and after therapy, CSCs display many responses including EMT, self-renewal, tumor environment, quiescence, epigenetic modification, MDR, and so forth. The mechanisms by which CSCs contribute to resistance against therapeutics are summarized.