Mrs Madhuri Sawant

Research project: Autophagic modulation of DNA damage signaling as a therapeutic avenue in Leukemia

Abstract

Acute Myeloid Leukemia, a type of Blood Cancer is dangerous and dreadful if untreated. The current treatment strategies involve various side effects and shows resistance towards the current therapeutics allowing the cancer to grow in-spite of appropriate treatment. Literature study demonstrates the link between DNA repair abnormalities in AML patients which can be exploited with DNA repair inhibitors. External and internal agents cause dangerous genomic attacks on all living organisms and are responsible for genomic lesions. A self-degradative mechanism known as Autophagy and DNA repair mechanism (to correct the damaged genes) are the biological pathways that maintain vital internal environment of cell. Autophagy exhibits both cytotoxic and cytoprotective functions under stressful conditions based on the extent of DNA damage and thus, accordingly DDR (DNA damage response) comes into action. This protective form of response promotes cancerous growth and is linked to the initiation progression and resistance towards the cancer therapy. Thus, inhibition of autophagic mechanism is studied and explored as a new therapeutic strategy to treat cancer. The aim of my PhD project is to find the hidden answers of how this regulatory mechanism can vary the genome correction mechanism (DNA Repair). The mechanism can be demonstrated by using autophagic inducers and inhibitors in AML cell lines to modulate DNA damage signally. Established DNA damage and repair assays will be conducted to further our understanding of genome stability in leukemogenesis, but also as a potential therapeutic strategy in combination with DNA repair inhibitors. Using the combinatorial treatment strategy i.e. modifying autophagic regulatory mechanism and suppressing the gene correction through inhibitors will I'll be able to investigate if it will open new gateway to finding out much effective cancer treatment