Abstract:
Cancer is a global problem with a high mortality rate and morbidity rate affecting 8.2 million
cases annually). The current treatment regimens for cancer include chemotherapy, radiotherapy
and anticancer drugs. Apart from being cancer therapeutics they have a lot of side effects and
cause problems like chemoresistance, mutagenesis, radiation induced mutations, secondary
tumorgenesis, limiting patient quality of life and survival. Therefore we need to focus on
molecular targeted therapies for cancer boosting the immune system. The current project
focusses on the combinational therapy for cancer involving in silico drug design(ST6Gal I
inhibitors) and biological therapy (Newcastle disease mediated virotherapy) to effectively
combat cancer.
Aberrant glycosylation is the hallmark of cancer cells regulated by sialyltransferases enzymes in
the cells. Out of these enzymes ST6Gal 1 belonging to the ST family is overexpressed in more
than 20 cancer types having roles in invaseness, chemoresistance and malignancy. The insilico
part of the study focuses on the use of aromatic and flavonoid compounds with potent biological activity as ST6Gal I inhibitors. Structure based approach was used in the study and the compounds were docked in the binding cavity of the enzyme and ligand-protein interactions were computed to understand the binding affinity and interactions of these compounds with the target site so that target hit molecules and lead compounds could be isolated from this approach
and use as potent inhibitors against ST6Gal .
The second therapeutic regimen investigates the role of New castle disease virus Pakistani strain with the cancer cells and its interactions with the innate immunity; interferon and apoptosis
pathway was studied. NDV effectively replicated in Hela cells effectively utilizing the RIG-
1/MDA5 pathway. The type 1 interferon was induced leading to the activation of JAK /STAT pathway. NDVPv uses the extrinsic pathway of apoptosis using the Fas/L death receptor pathway using caspase 8 leading to intrinsic pathway of activation independent of NF-KB pathway.
