Project description
Smart drugs against cancer
Many chemotherapy regimens such as cisplatin target DNA, causing non-specific side effects in normal cells. Therefore, there is a pressing need for new, more specific and effective anti-cancer drugs. The EU-funded G4Redox project addresses this problem by developing compounds that leave double-stranded DNA intact and target transient G-quadruplex DNA structures that form during replication and transcription. Moreover, these drugs become activated only in the presence of low oxygen levels such as in the case of the tumour microenvironment. Researchers envision combining these drugs with other anti-cancer pharmaceuticals for a synergistic effect.
Objective
Cancer is the second leading cause of death globally. In spite of the great advances in cancer therapy over the past two decades, there is still a pressing need to develop new therapies with reduced side effects caused by conventional therapies. Historically, many chemotherapeutic approaches to treat cancer, have targeted DNA. But targeting genomic DNA has some disadvantages such as undesired side effects due to low selectivity of most chemotherapeutics (e.g. cisplatin and alkylating agents).
In this project I aim to address this problem via the development of ‘smart’ compounds that have the following features: (i) target G-quadruplex DNA structures instead of duplex DNA; this non-canonical DNA topologies form transiently during replication and transcription (as well as in the telomeric region) and have been identified as attractive targets for anticancer drugs (ii) developing compounds that are only activated in tumors and not in healthy tissue to achieve this, I have designed pro-drugs that are only activated in the hypoxic (low levels of oxygen) conditions present in tumors and only when activated can target G-quadruplex DNA (iii) my ‘smart’ compounds will not only target G-quadruplex DNA once activated but will release a second drug able to target other cancer molecular targets (e.g. topoisomerase I, COX-2) to cause a cumulative response of the chemotherapeutic agent. I expect to see significant synergism between the different chemotherapeutics released upon activation of the pro-drug. This synergy in the activities is expected to play an important role to overcome drug resistance. The multidisciplinary nature of the project is strong. The proposal includes both way transfer of knowledge between the host group at Imperial College of London and the candidate in new advanced skill sets and techniques. The proposed work will expand my experience, research competencies, and professional networks, enhancing the development of my career as an independent researcher.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
SW7 2AZ LONDON
United Kingdom