Research Projects

Cancer is one of the leading causes of death despite the tremendous advancements in the treatment strategies. In general, cancer treatments are directed to eliminate the rapidly proliferating abnormal cells by means of chemotherapy, surgery and radiation. However conventional treatments with general chemotherapeutic agents are less effective owing to low specificity and high toxicity issues. Therefore, targeted therapy which promises more specificity and less side effects has been preferred. Targeted therapy can discrete cancer cells from normal cells based on tumour markers and thereby improve specificity and cytotoxicity to normal cells. Targeted therapy involves the use of specific inhibitors or antibodies (immunotherapy) to selectively recognise and interact with the corresponding target proteins which are expressed or over expressed in cancers in comparison with their normal counterparts. However, targeted therapy has been found to impart varying degree of sensitivity in patients. In addition, initial responders to targeted therapeutic regimes are found to become insensitive due to acquired drug resistance and thus leading to treatment failure. Aggressive tumor cells have found to undergo cellular modifications in response to intrinsic and acquired mutations over time in to a heterogenous lump. Glycosylation is a key cellular mechanism regulating such cellular modifications. Altered glycosylation in terms of exaggerated expression of glycoproteins, glycosphingolipids and proteoglycans, has been well documented to promote aberrant proliferation of cells, loss of contact inhibition, promoting intratumor heterogeneity, metastasis and therapy resistance. Thus, strategies to regulate glycosylation can be considered as a potential therapeutic target to alleviate therapy resistance of aggressive cancers. In addition, altered glycosylation of tumor cell resident surface proteins have found to impart therapy resistance towards targeted therapeutic strategies directed against this protein. In this background, here we propose to validate the potential of already existing glycosylation inhibitors as possible anti-cancer agents to sensitise such therapy resistant aggressive cancer subtypes subjected to targeted therapeutics. We will also evaluate the toxicity imparted by these agents in cancer cells to assess their potential to serve as drug candidates in combination with conventional or targeted therapy. The major enzymes implicated in glycosylation include glycosyltransferase and glycosidase. The present study also expects to identify novel glycosyltransferase and glycosidase inhibitors from natural sources and synthetic methods as glycosylation inhibitors.