Kanaga Sabapathy; Suresh Mathivanan
Competition Sponsor: Ministry of Health and National Research Foundation of Singapore
Awardee year: 2021
Ageing results in increased propensity for cancer development, due to the accumulation of mutations over the life-time. Not surprisingly, cancer incidence is on the rise globally. If left unchecked, the outlook is dismal. Treatment modalities alone will be insufficient to tackle the impending “cancer tsunami”. This proposal is therefore driven by the need of the hour, and is aimed at establishing the concept of “molecular cancer prevention” to reduce cancer incidence in the ageing population. It is based on the idea of enhancing one’s own tumor-suppression mechanisms to prevent damaged cells from turning malignant. p53 is the master tumor-suppressor gene that prevents cancer development. Using mice expressing additional p53, we have shown that elevating p53 levels can indeed significantly delay the development of cancers. To translate these initial findings, we are proposing to provide exogenous p53 using extracellular vesicles (EVs) that we have developed, to increase an individual’s tumor-suppression capabilities. This, in essence, constitutes a prophylaxis model whereby the exogenous p53 will enhance the body’s vigilance against cancers. We will evaluate the efficacy of the p53EVs for their ability to induce a p53 response, establishing the proof-of-concept for a molecular cancer prevention strategy to keep the aged cancer-free.