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Abstract

Traditional therapies do not kill cancer progenitor cells and drug-resistant cancer cells, causing cancer relapse. Interestingly, combination therapy, including epigenetic drugs, was effective against breast and ovarian cancers causing more than additive growth inhibition in various types of breast and ovarian cancer cells. Our recent analytical study suggests that breast and ovarian cancers possibly have similar epigenetic origin. Other studies have shown that combination therapy with epigenetic drugs reduced cancer relapse, sensitized drug resistant cancer cells, and killed cancer stem cells. These findings led us to hypothesize that initiation of cancer progenitor cell formation from predisposed cells requires an epigenetic switch. Further development of cancer involves mutations. This hypothesis contradicts current paradigm of carcinogenesis. CpG residue methylation in the upstream regions of genes is one of the epigenetic regulations involved in silencing of tumor suppressor genes in cancer cells. In addition, histone modifications, such as H3K4me, and H3K27me3, and other histone modifications regulate gene expression in concert with alterations in DNA methylation. Our system biology analysis revealed that DNA methyl transferase1 (DNMT1), the enzyme which maintains CpG residue methylation is allosterically activated in cancer cells. H3k9me3 recruits DNMT1 at the site of CpG methylation. It is possible that histone modification and CpG methylation work in a concert to regulate differential gene expression in carcinogenesis.

Biography

Email: ssarkarw@gmail.com