Contribution of nuclear events in generation and maintenance of cancer stem cells: revisiting chemo-resistance

Abstract

While chemotherapy is often capable of reducing the tumor bulk, disease-free survival of patients is curtailed by recurrence because of chemoresistance. In fact, the cardinal reason of treatment failure can be attributed to chemoresistance, which involves a complex mechanism. In the present scenario, cancer stem cells (CSCs) have been identified to play a pivotal role in chemoresistance. A few reviews have discussed numerous mechanisms of chemoresistance in CSCs and the therapeutic strategies targeting stem cell signaling pathways. References are also there elaborating the applications of therapeutic nanoparticles and epigenetic drugs in targeting CSCs. However, there is a paucity of information in this area that should be explored and addressed. It is a well known fact that the nucleus harbors the entire genome of an organism and is the master regulator of all the genetic and epigenetic programs. In fact, majority of the features of CSCs evolve from cell nucleus. Here we review, the prevailing and emanating concepts of how the key nuclear events like (1) genetic regulation, (2) epigenetic regulation, (3) regulation by microRNAs (miRNA), and (4) DNA repair, can influence CSC properties like (a) induction of EMT (epithelial-mesenchymal transition), (b) self renewal, (c) drug resistance, (d) cellular plasticity, and (e) pluripotency, thereby finally aiding in chemoresistance and cancer recurrence. Information obtained from the discussion will help in revisiting chemoresistance and provide approaches for treating CSCs by targeting nuclear events, thereby improving the prognosis and survival rate of cancer patients in near future.