Outsmarting cancer - new results from novel enzyme inhibitors

Smart drugs that can break the chain of command between enzymes and the genes involved in cell division and cell death are a new way forward in tackling breast cancer, according to Dr Stephen Johnston, a consultant oncologist from The Royal Marsden Hospital, London, UK.

Presenting results from the worlds first phase II trial of R115777 (Zarnestra) in breast cancer, Dr. Johnston said that among 41 women with advanced cancer who had previously undergone chemotherapy or hormone treatment, four had a partial response from the new drug and in a further six the disease had been stabilised over a prolonged period. Trials are now planned combining R115777 with chemotherapy or hormone therapy, as laboratory studies indicate that the new drug acts synergistically with conventional treatments to boost their effectiveness.

R115777 is one of a novel drug class called farnesyl transferase inhibitors, he told a news briefing at the 3rd European Breast Cancer Conference in Barcelona. Farnesyl transferase is an enzyme that enables a protein called Ras to function and signal correctly within the cell. Ras plays a prominent part in many types of tumours. Although it is rarely directly mutated in breast cancer, Ras often receives signals from growth factors that make it function in an abnormal way, promoting the growth of breast cancer cells. Interrupting the cellular signals by targeting Ras breaks the chain of command between the growth factors and the nucleus of the cell and appears to inhibit the growth of the cancer cells. In addition, several other proteins involved in cell growth and motility may also be farnesylated and so may also be targets for farnesyl transferase inhibitors.

Another key enzyme the 26S proteasome is also in the firing line for smart drugs. Proteasome is a protein complex that modulates the behaviour of cells during the cell cycle. It regulates the levels of key proteins that control the fine balance between normal cell division

Contact: Margaret Willson
Federation of European Cancer Societies

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