Missing protein provides clue to ovarian cancer drug success

Dec 10 2007

Scientists have discovered a protein which could improve the success rate of the tumour shrinking drug paclitaxel, in the treatment of ovarian cancer, a study reveals in Cancer Cell.

The researchers, funded by Cancer Research UK and the Medical Research Council, found that the loss of a protein called TGFBI caused paclitaxel to fail.

Paclitaxel, part of a family of drugs called taxanes – originally derived from yew trees – is a common chemotherapy treatment for ovarian cancer. However, only 50 per cent of patients respond well to the therapy.

The authors, based at Cambridge Research Institute, at Cambridge University, examined ovarian cancer cell lines and data from 20 patients in a prospective trial. Those who showed no response to the drug had less TGFBI in their pre-treatment samples compared to those whose condition improved. Studies after treatment revealed that death of cancer cells occurred where levels of TGFBI were high.

Ovarian cancer is one of the hardest cancers to detect at an early stage and is the fourth most common cancer in women, with 7,000 cases diagnosed in the UK each year. The study suggests that patients who lack the protein could be spared from chemotherapy which will not benefit them.

Lead researcher and clinician, Dr James Brenton, said: "TGFBI is lost in one third of primary ovarian cancers and it is possible that this protein could be used as a biomarker for selecting patients likely to respond to this class of drug.

"Our findings offer hope not only for improved ovarian cancer treatment, it may also lead to improvements in the success rate of other taxane drugs used to treat lung and breast cancer."

Dr Ahmed Ashour Ahmed, Cancer Research UK clinician scientist, and first author of the paper, said: "Our work reveals that some proteins that surround cancer cells such as TGFBI send messages to microtubules, the backbone of the cell, sensitising them to paclitaxel. Deciphering the code by which these messages are sent will enable the discovery of new treatments that will simulate the coded messages leading to a significant improvement in paclitaxel response."

Prof Herbie Newell, Cancer Research UK's director of translational research, said: "We are entering a period of cancer treatment where more drugs are targeted at those people who will benefit the most. This personalised medicine approach potentially means treatments will be more effective with fewer side effects. This is really important for diseases like ovarian cancer that can be challenging to treat."

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