"The past decade has seen substantial advances in our understanding of cancer molecular biology and the technologies available to study it, emphasising the importance of the molecular mechanisms of carcinogenesis in cancer research. We now face having to therapeutically aim for many less common targets rather than a few all-cancer present targets. Effective single molecular targets therapies are generally not sufficient to elicit durable clinical responses and the development of drug resistance is an increasing problem. Consideration of only a single drug–target interaction in vivo has proven to be overly simplistic.
The ultimate goal of this proposal is to generate metallodrugs whose mechanism of action is understood and whose targets are identified. These multitargeting drugs would be a more realistic option by leading rational co-extinction strategies for specific cancers.
Current cross-discipline trainings make possible the alliance of inorganic chemistry with cell and molecular biology. The unprecedented potential for design of metallodrugs has not been overseen and medicinal bioinorganic chemistry is rapidly expanding.
This interdisciplinary proposal involves chemistry, biology and physics, with potential not only for the discovery of novel medicines for cancer treatment, but also for the development of new methodologies to modulate and deconvolute the technology behind the tumour cell machinery. By uncovering the operating principles and mechanisms of action of our metallodrugs at the nanoscale (i.e. subcellular level) we aim to inform on what biological context its destruction would lead to cell death and also to tumour regression.
These metallo-medicines will exploit the extraordinary features of transition metal complexes, in particular the capability for in tumour activation, and the possibility of being loaded into nanocarriers, conferring control on the drug reactivity, and thus minimising undesired side effects, often responsible for drug failure."
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