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Enhanced efficacy of bioactive compounds: Targeting isoprenylation in cancer cells to mediate apoptosis.

Collaborator: Prof. M T Camilleri Podesta

The mevalonate pathway has a central role in signal transduction regulating cell survival and apoptosis. The rate limiting enzyme in this pathway is HMG CoA reductase (Hmgcr), which is regulated at multiple levels. In a wide variety of cancers, isoprenoids are potent inducers of cell apoptosis. However, effective doses were poorly tolerated in clinical studies. The main objective of this project is to optimise anti-cancer treatment with isoprenoids by establishing a combinatory treatment. The scientific innovation involves the proposed combination therapy of isoprenoids and rapamycin (immunosuppressant and anti-cancer drug CCI-779). Rapamycin will enforce apoptosis induction upon treatment of cancer cells with isoprenoids, hence enhancing therapeutic index.
The main objective of this project is to optimise anti-cancer treatment with isoprenoids by establishing a combinatory treatment. To achieve this objective, we propose an approach in which we address the molecular and cellular basis to enhance the effectiveness of anticancer drugs by a combination of therapies aimed at specific induction of apoptosis in cancer cells.

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Last Updated: 12 December 2008

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