Executive Summary : | A multidisciplinary research group at TIFR-Mumbai aims to improve the cancer selectivity, drug efficacy, and safety profile of platinum anticancer drugs and drug candidates by harnessing the cancer targeting properties of the natural product bleomycin-A5. The group aims to address key questions such as the conjugation of the sugar unit of bleomycin-A5 to platinum drugs, the development of next-generation cancer targeting vectors, and the improvement of sugar-mediated delivery in platinum chemotherapy. Cancer is the second leading cause of mortality worldwide, and chemotherapy is the front-line treatment choice for many cancers. However, platinum-based drugs have numerous shortcomings, such as a lack of tumor selectivity, sub-optimal dose accumulation, and severe toxic side effects such as neuro- and nephrotoxicity. To address these shortcomings, the group plans to harness the cancer targeting ability of the naturally occurring glycopeptidic anticancer agent Bleomycin A5. They propose synthesizing bioconjugates of clinical platinum anticancer drugs and novel platinum drug candidates with the truncated sugar unit, which is responsible for high cancer-seeking abilities of Bleomycin A5. These novel conjugates are expected to accumulate selectively in cancer cells, avoiding accumulation in healthy tissue, improving efficacy and reducing adverse side effects. The outcomes and knowledge obtained from this project would be a significant leap forward for the entire field of drug discovery and development, as well as the potential development of a new class of safe anticancer drugs. |