Mechanisms of chemoresistance in cancer stem cells

Our understanding of cancer has changed over the years, owing to rapid advances in oncology research. The disease itself is not only characterized as a mass of excessive, uncontrolled growth of abnormal cells but is also defined by the dynamic alterations in the genome that cause cancer [1]. Left unchecked, cancer progression leads to disruption of normal biological processes via cellular invasion into local adjacent tissues and distal organs through metastasis. In addition to conventional cancer treatments such as surgery, radiation and cytotoxic chemotherapy, more selective treatments based on increased understanding of tumor biology and specific tumor subtypes have also become available [2]. Even with these advances in cancer therapy, chemotherapy remains an important component of cancer treatment. Currently, the complete elimination of cancer continues to elude oncologists as 90% of drug failures in metastatic cancers are attributed to chemoresistance [3]. Understanding the mechanisms by which chemoresistance can occur is important to developing novel therapeutic approaches to treating cancer.In some cases, intrinsic chemoresistance may result in the survival of a population of tumor cells that subsequently leads to recurrence following treatment. This may be particularly true for tumors that are composed of a heterogeneous population of cells. For heterogenous tumors, the tumor initiating potential and drug sensitivity of different tumor cells within the same tumor bulk has yielded two models of cancer initiation: the stochastic model and the hierarchical model [4]. The stochastic model proposes that there is no variation in tumor initiating potential among different tumor subpopulations and that tumor cell growth is dependent on immune response, microenvironment and intrinsic gene regulatory signals. In contrast, the hierarchical concept suggests that different subpopulations of cells within a tumor have varying levels or absence of tumor initiating potential.