Resistance and DNA repair mechanisms of cancer stem cells: Potential molecular targets for therapy

Abstract

Cancer stem cells (CSCs) are small subpopulations of cells within tumors that are intricately related to both de novo and acquired resistance to conventional therapies leading to tumor recurrence and metastasis. A majority of cancers initially respond to chemotherapeutic agents, as well as radiation therapy, but eventually develop resistance. An increased understanding of CSCs has led to the discovery that current treatments target the differentiated cancer cells leaving the CSCs unscathed due to their robust signaling pathways. Further, maintenance of genomic fidelity is important for normal functioning and survival of cells, including cancer cells and the CSCs. In this chapter, we will discuss several such pathways/phenomena which help CSCs resist therapies. These include increased quiescence and up-regulated drug transporters, activated DNA repair mechanisms and activation of several key cellular signaling pathways (Fig. 3.1). A better understanding of these resistance pathways is a necessary prerequisite towards the ultimate goal of developing novel strategies specifically targeting CSCs. Better designed therapies could ultimately reverse their resistance and thereby eliminate the potential of tumor recurrence and metastasis.