Cell's cytoskeleton may hold key to overcoming drug resistance in cancer

Oct 4 2007

Researchers have uncovered a new way in which a cell protein protects cancer cells from a wide range of chemotherapeutic drugs, identifying a possible target for improving treatment outcomes for patients.

A team of scientists at Children's Cancer Institute Australia for Medical Research (CCIA), led by Associate Professor Maria Kavallaris, discovered that the bIII-tubulin component of the cell's cytoskeleton could play an important role in resistance to a wide range of drugs used to treat lung, ovarian and breast cancers.

Advanced non-small cell lung carcinomas (NSCLC) account for more than 80 per cent of lung cancer cases. More than one million people are diagnosed with lung cancer every year, the most common cancer in the world and the leading cause of cancer deaths. Chemotherapy remains the most effective treatment option, involving a diverse range of drugs, often used in combination. However, the emergence of drug-resistant tumours in NSCLC means chemotherapy no longer holds the promise of a good outcome for many patients.

Increased expression of bIII-tubulin has been linked to drug resistance in NSCLC, ovarian and breast cancers. In the latest Cancer Research publication, Associate Professor Kavallaris and her team showed that blocking the expression of the bIII-tubulin gene in NSCLC cells led to an increase in their sensitivity to a range of chemotherapeutic drugs.

“Our results strongly suggest that the bIII-tubulin component is responsible for protecting NSCLC cells from the action of key chemotherapeutic drugs,” said Associate Professor Kavallaris.

“This is the first scientific evidence for the broader implications of abnormal expression of this protein.

“We now have new insight into a mechanism of drug resistance in NSCLC which has not previously been reported. This has important implications for improving the targeting and treatment of a number of cancers which are resistant to current chemotherapeutic drugs,” said Associate Professor Kavallaris.

http://www.ccia.org.au/