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Last Updated: Wednesday, 11 July 2007, 07:52 GMT 08:52 UK
Fighting back against cancer
By Geraldine Fitzgerald
Producer, BBC Radio 4's Rise of Resistance

When Guardian columnist Dina Rabinovitch was diagnosed with breast cancer in 2004 she was prescribed the much sought-after drug Herceptin - but she had no idea that the drug could cease to have the desired effect.

"I had no sense of being resistant to cancer drugs," she said.

Dina Rabinovitch
Dina Rabinovitch failed to respond to treatment

"But as the cancer kept coming back I started to understand it in terms of antibiotics - or lice treatments, because of treating my kids for lice.

"You can have a treatment for a while and then you have to switch to something else. That's how I think of cancer treatment now."

Dina, author of "Take off your Party dress - when life's too busy for breast cancer", has a type of cancer, known as HER 2, which was traditionally more difficult to treat than other types of breast cancer.

Her oncologist was at a Florida conference where the findings of the first Herceptin trial were presented - and he was enthusiastic about what he had heard.

"I remember sitting in the room with him and he said: 'Oh, you've heard about it. I must tell you this is the first time in my experience we have seen results like this, where the line for recurrence was going down'."

Genetically unstable

Dina had 18 doses of Herceptin, but during that time her cancer came back twice.

With these new approaches we can search for mechanisms of resistance
Dr Lyndsay Harris
Yale University

"I proved to be one of the people who either have no response to Herceptin or it had some effect for six months or so, but the cancer came back and developed this resistance so the drug stopped helping me."

Cancer cells develop resistance because they are genetically unstable cells and through natural selection they evolve to evade the drugs in a variety of ways.

Herceptin works by interfering with one of the ways in which breast cancer cells divide and grow.

Some breast cancer cells divide and grow when a protein, known as human epidermal growth factor, attaches itself to another protein, HER2, found on the surface of some breast cancer cells.

Herceptin blocks this process by attaching itself to the HER2 protein so that the epidermal growth factor cannot reach the breast cancer cells and they cannot divide and grow.

Lyndsay Harris, associate professor of Medicine at Yale University, thinks women who develop resistance to Herceptin do so because the growth factor finds another protein on the surface of the cancer cell to attach itself to, undermining the effect of Herceptin.

Predicting resistance

Professor Harris believes that understanding the mechanisms cancers use to side step drugs will eventually enable doctors to predict resistance.

Herceptin
Herceptin can produce striking results

"We can look at tumour tissue from patients who have developed resistance to the therapy for markers of resistance," she said.

"The technology allows us to look at thousands of genes and proteins at the same time. With these new approaches we can search for mechanisms of resistance - and then determine for patients on particular therapies what is likely to be the mechanism of that resistance."

If Professor Harris' work goes well doctors will be able to change a patient's treatment as soon as their drugs begin to fail.

Small cell lung cancer is a cancer with the ability to develop resistance to many drugs.

Professor Michael Sekyl of Imperial College London has discovered there is a growth factor in the cancer cells which acts as a "master switch."

"This particular growth factor is able to turn on a master regulator inside cells which up regulates a series of molecules in the cells that stops them from dying when we give them the chemotherapy drug," he said.

"This isn't just one chemotherapy drug it's a multiple of chemotherapy drugs which would normally cause the death of the cells "

Professor Sekyl and his colleagues are working to develop a way to remove the master switch from the cell and reactivate chemotherapy.

Across the globe scientists like them are gaining a greater understanding of drug resistance. With each new discovery a new dawn of specifically tailored treatments comes ever closer.

Rise of Resistance is broadcast on 4 and 11 July, 2100 BST, BBC Radio 4.
Each episode is available for seven days after broadcast at Radio 4's
Listen again page.




SEE ALSO
Herceptin 'shown to save lives'
05 Jan 07 |  Health

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