NCRI conference: making progress in treating ovarian cancer

Professor Stan Kaye addresses the NCRI conference

When the Institute of Cancer Research’s Professor Stan Kaye first started treating ovarian cancer patients in the 70s, survival rates were very low – only 15 per cent of women survived for five years or more after being diagnosed.

But as new treatments were discovered and moved into widespread use, that figure began to rise.

Nowadays, forty per cent of women survive for five or more years, and there are more improvements on the horizon.

At the NCRI conference, Professor Kaye took us on a guided tour of the history of ovarian cancer treatment, and looked at some of the exciting developments that he and others are working on.

Humble beginnings

The first major advance came with the use of cisplatin and then carboplatin – two drugs that Cancer Research UK helped develop. This was swiftly followed by the adoption of paclitaxel.

These chemotherapy drugs led to significant improvements in survival but, as Professor Kaye pointed out, one of the major advances was the recognition of the importance of high-class surgery.

In fact, a 2005 study of international approaches to surgery showed that proper ‘tumour-debulking’ surgery, carried out by trained ovarian cancer surgeons, was found to be at least as important in improving survival rates – a salient message in an era of ever-increasing drugs costs.

Understanding drug resistance

Drug resistance is a well known problem in ovarian cancer – many women initially respond well to a given treatment, only to relapse later. We’ve written before about ongoing research into this problem, and Professor Kaye highlighted several other avenues of research, particularly the work of Professor Bob Brown at the Institute of Cancer Research, who’s looking at the role of stem cells and a process called ‘mismatch repair’ in driving the drug resistance.

Targeted treatments

Professor Kaye then turned his attention to two new drugs that are currently being trialled in women with ovarian cancer – bevacizumab and olaparib.

Bevacizumab, also known as Avastin, is a drug that alters the growth of new blood vessels. It’s been tested for a variety of cancers, and has shown particular promise in ovarian cancer treatment, particularly when given during and after chemotherapy. Two large trials have been carried out so far, GOG-218 and ICON-7. Results from both trials were encouraging (and further results from ICON-7 are beingpresented later today), but there are many unanswered questions.

For a start, bevicizumab’s effects seemed to wear off soon after stopping treatment during the trial. In addition the drug is very expensive, so it’s crucial that researchers find out how to make the most of the drug’s ability to control the disease.

The second drug exciting Professor Kaye was olaparib – a name that will be familiar to regular readers of this blog. It’s a type of drug called a ‘PARP inhibitor’, which targets cancer cells that have a particular molecular defect; Cancer Research UK scientists have been heavily involved with the drugs’ development over the years.

Most of the focus on olaparib has been in treating breast cancer, but recently a few trials have looked at its potential for treating ovarian cancer. Professor Kaye flagged up one particular trial, presented at the ASCO 2010 conference in the US this summer. The trial followed 55 women with ovarian cancer who were given olaparib – eleven of them responded well to the drug for an average of 31 weeks, and the researchers saw a partial response in another three of the women.

But this means that 41 out of the 55 women got no benefit from the drug. Clearly there’s a real need for a quick, efficient test to work out who will and won’t respond to the drug – and Professor Kaye hinted that, excitingly, this was closer than we thought. And he talked about a large, randomised trial that will be presented at next years’ ASCO that “will be very important”.

Other promising avenues

In wrapping up, Prof Kaye briefly discussed two other promising avenues to target ovarian cancer. The first of these was the “PI3 Kinase” pathway – a signaling network inside our cells that is often hyperactive in ovarian cancer. Professor Kaye’s colleague at the ICR, Professor Paul Workman, has led a team that’s developed a molecule, called GDC-0941, which can dampen down this erratic signalling network, and this drug is now in clinical trials.

The final target of attack Professor Kaye discussed was a molecular receptor called the alpha-folate receptor which, again, is more common on the surface of ovarian cancer cells, and which appears to encourage them to grow. Several teams are developing ways to switch this receptor off, and again, many of these are now in trials.

Professor Kaye’s real hope for the future was not that any of these treatments might on their own be a ‘magic bullet’ for ovarian cancer. He thinks that, instead, they offer doctors an ever-growing ‘tool-kit’ of options with which to treat patients, and that the trick will be to work out how to match the right treatment to the right patient.

“Remembering who it’s for”

To close his talk, Professor Kaye reminded us all why we were here, and what cancer research was for, by reading an excerpt from a letter sent to him.

The letter was from an 80 year old woman who had just attended her grandson’s 6^th birthday party. She’d been diagnosed with ovarian cancer before he was born.

That, said Professor Kaye, is testament to the progress we’ve already made. Hopefully, if all goes to plan, many more such letters will be written in the future, as we reap the rewards of the research going on around the world today.

Henry