JOURNAL ARTICLE

Identification of the specific epigenetic alterations associated with chemo-resistance via reprogramming of cancer cells

Jong Joo Kim, Rajani Rai
Medical Hypotheses 2015, 85 (6): 710-4
26527497

BACKGROUND: Chemo-resistance is the main obstacle in cancer therapy, limiting the effectiveness of drug treatment. Epigenetics-mediated changes are suggested as a critical factor paying the chemo-resistance phenotype. Since epigenetic modulations are a reversible phenomenon, reversion of epigenetic changes represents a promising therapeutic approach for cancer. However, heterogeneity in epigenetic marks in tumor cells makes it difficult to identify the specific epigenetic aberrations contributing to chemo-resistance. Our hypothesis aimed to explore this issue to add therapeutic options for cancer.

PRESENTATION OF THE HYPOTHESIS: Epigenetic alterations, the main mediator of cellular reprogramming, occur rapidly upon exposure to chemotherapy. Recent studies have demonstrated that reprogramming resets/erases the epigenetic marks established during differentiation to specific somatic cell types. To overcome the heterogeneous nature of cancer cells, we will attempt to make homogenous cancer cell colonies by reprogramming. Comparison of the drug-resistant cancer cells obtained from these colonies to parent cancer cells and reprogrammed cancer cells is an effective way to determine the precise epigenetic alterations underlying specific chemo-resistance.

TESTING THE HYPOTHESIS: Cellular reprogramming of cancer cells led to generation of homogenous colonies. Following lineage specification and long term drug treatment, the obtained drug resistance cells will be compared with parent cancer cells for whole genome epigenetic signature.

IMPLICATIONS OF THE HYPOTHESIS: A key implication of this hypothesis is that determination of the usefulness of cellular reprogramming of cancer cells enabling the identification of specific epigenetic modulation associated with particular drug resistance will enable exploration of new research avenues for cancer treatment.

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