Chemical modulation of cellular redox balance for cancer treatment

Platinum complexes, cisplatin, oxaliplatin and carboplatin, are the most widely used anticancer drugs. However, these DNA-targeting treatments are a low selectivity approach with deleterious consequences and a high incidence of resistance. The societal need for new anti-cancer drugs is very substantial, hence, the commercial demand for new anti-cancer agents is very high. Although targeted chemotherapeutics with novel mechanisms of action (for example kinase inhibitors) have been developed more recently, these often have a much narrower clinical utility than platinum-based drugs and generally suffer from rapid onset of resistance, which means that there is still a large unmet clinical need. Hence there is a wide interest in new metal-based drugs with alternative mechanisms of action.

The chemical scaffold offered by metal-based complexes has significant scope for molecular diversity and has the possibility of accessing chemical reactions beyond reach of organic molecules alone. Furthermore, these complexes could effectively be harnessed to target the redox balance in cancer cells and induce both oxidative and reductive stress, perturbing the cellular balance of reactive oxygen species. Cancer cells are primed for this intervention, because they are already redox-hyperactive and in most cases present malfunctioning mitochondria. Dysfunctional mitochondria are unable to control ROS generation efficiently. This allows metal-based complexes, to exert selective toxicity towards cancer cells over normal cells. The design of such drugs is relatively unexplored and, even more so, is their MoA at cellular level.

The research in my group aims to develop metal complexes which will target this redox balance in cancer cells. It includes the synthesis and characterisation of novel metal-complexes and the subsequent investigations of their cellular behaviours. Understanding the mechanism of action at cellular level will allow the development of an improved second generation of chemotherapeutics. This strategy offers a ground-breaking possibility to combat tumour resistance, reduce side-effects and expand the range of treatable cancers.

Person Specification: Applicants should have a background in synthetic organic or inorganic chemistry, or medicinal chemistry and/or biochemistry. They should be willing to extend their areas of expertise and get involved with cancer cell culture and general cell biology.

Informal enquiries should be directed to Dr. Isolda Romero-Canelón.
Email: [Email Address Removed]

To be considered for the studentship, please send the following documents to [Email Address Removed]:
- A detailed CV, including your nationality and country of birth;
- Names and addresses of two referees;
- A covering letter highlighting your research experience/capabilities;
- Copies of your degree certificates with transcripts;
- Evidence of your proficiency in the English language, if applicable.