Microtubule stability linked to increased sensitivity to paclitaxel

Sep 2 2011

SCIENTISTS have discovered how blocking key cell signalling proteins could help boost the success rate of the tumour-shrinking drug paclitaxel, according to a study published in the journal Cancer Research today.

Paclitaxel is one of a family of drugs originally derived from yew trees that block the growth of cancer by interfering with microtubules - structures that help chromosomes to separate during cell division. It's commonly used to treat breast and ovarian cancer, but some tumours can become resistant over time and start growing again.

The international team of researchers, - funded by Cancer Research UK, the University of Oxford and, the Camilla Samuel Fund, and the University of Texas M.D. Anderson Cancer Center - found that blocking certain proteins stabilised the microtubules and made ovarian cancer cells more sensitive to paclitaxel.

Lead researcher Dr Ahmed Ahmed, based at the University of Oxford, said: "Our work provides further evidence for the important link between the stability of microtubules, the backbone of the cell, and sensitivity to paclitaxel. And because the proteins we've identified share the same target as paclitaxel, it raises the prospect of developing more specific drugs that sensitise cancer cells to paclitaxel without damaging the surrounding tissues."

Previous research by Dr Ahmed and colleagues found that the loss of a protein called TGFBI - which sends messages that stabilise the microtubules - caused paclitaxel to fail.

So to test the theory that microtubule stability may be essential for paclitaxel response, the researchers systematically blocked other signalling proteins in ovarian cancer cells growing in the lab, to see which might alter paclitaxel response.

Senior Author Dr Robert Bast, vice president of translational research at the University of Texas MD Anderson Cancer Centre, said: "Our study has revealed several new proteins involved in microtubule stability that could be potential targets for drugs to improve the sensitivity of cancer cells to paclitaxel, without damaging healthy cells."

Dr Julie Sharp, senior science information manager at Cancer Research UK, said: "Overcoming drug resistance is a key challenge for our researchers. Unravelling the genetic basis of cancer to find out what determines whether a patient will respond to treatment will help us take a more targeted approach to tackle this problem. This approach could lead to fewer side effects and provide a lifeline for patients who have stopped responding to conventional treatments."

Source: Cancer Research UK