Delta
G
New therapies from understanding ageing
Delta
G
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Cancer is the second most common killer in the Western World, and one of the most feared. Unlike heart disease and diabetes (between them the most common threats to health and life), diet, exercise and healthy living will do little to stave off cancer once the process starts. This is because cancer is a disease of uncontrolled cell proliferation: cell growth rather than cell death.
Conventional drug approaches to cancer target this cell growth, though inhibitors of DNA replication, cytotoxic agents that selectively affect growing cells, and the newer drugs such as Tarceva and Herceptin that target the molecular mechanisms that allow cancer cells to continue to grow when they are not meant to. Nearly all therapeutic approaches that are in research or in clinical trials, including those that target apoptotic mechanisms (such as bcl-2 or p53 pathways), those that target angiogenesis, and those that use sophisticated genetic constructs to target cells without normal replicative or apoptotic machinery, still 'go after' uncontrolled growth as a key distinguishing factor.
Delta G takes a new approach. It has been known for over 50 years that energy metabolism in cancer cells is abberant. The science behind Delta G has identified unique aspects of the switch from normal respiratory energy generation to 'fermentative' energetics that can be a unique target in cancer cells. Delta G is developing drugs that shoot at this target, attacking what cancer cells are rather than what they do. This is particularly relevant to the treatment of advanced cancers, which are often resistant to conventional therapy because they have 'evolved' resistance to most anti-cancer drugs, and are composed mostly of cells that are not dividing.
We are using rho-0 cells as models for the cells that cannot carry out oxidative phosphorylation at the cores of advanced tumours. Ian Holt, our collaborator at the MRC, is a leading expert in mitochondrial cell biology, and particularly in the generation of rho-0 cell lines. These cells can be used in conventional screens for new molecules.
We have identified two series of compounds that kill rho-0 cells spelectively compared to syngenic rho-+ cells. Based on these early hits, we are developing molecules that can be tested in models of late-stage cancer.
(Rho-0 vs rho-+ selective killing. Delta G data, September 2005
We are presently filing patents on many aspects of this technology. Expect more on this exciting science in early 2006!