Why Taxol Works Better in Some Patients Than Others
the Cancer Headlines®
January 22, 2003
An intriguing clue as to why some
tumors respond less well than others to an important class of anti-cancer drugs
has been uncovered by scientists from Cancer Research UK and the Medical
Taxol and similar drugs target the
process of cell division and are used for treating a number of late stage
cancers, including breast and ovarian tumors. But researchers have found that
high levels of a molecule called AURORA-A within cancer cells could make Taxol
Their discovery – revealed in a
laboratory study published in the journal Cancer Cell, will now be tested
in cancer patients. If confirmed, it could be used to devise a test to predict
the effectiveness of Taxol-type drugs, allowing treatments to be planned for the
individual patient. The research could also pave the way for future cancer
Drug resistance is one of the biggest
problems facing cancer doctors. Supplementary drugs aimed at increasing the
effectiveness of chemotherapy could save many lives – but first scientists
need to identify the key mechanisms of drug resistance and find ways of
In the new study, headed by Professor
Ashok Venkitaraman, scientists from Cancer Research UK and the University of
Cambridge looked at the role of the AURORA-A molecule. AURORA-A is found at
higher than normal levels in up to half of breast and bowel tumors, as well as
in many other kinds of cancer.
Researchers genetically engineered
cervical cancer cells with the gene for AURORA-A in order to increase levels of
the molecule. When treated with Taxol, only about half as many engineered cells
were killed by the drug as non-engineered cells.
Professor Venkitaraman says:
"High amounts of AURORA-A seemed to make cancer cells less sensitive to
treatment. Testing tumors for the molecule might help us to predict how
effective Taxol treatment is likely to be. Of course, our findings will need to
be confirmed in cancer patients before it is clear that such a test will
"Our work raises the additional
possibility that new drugs which inactivate the molecule could boost the
response of cancer cells to treatment."
Scientists also investigated precisely
how the molecule might affect the response of cancer cells to Taxol treatment.
Normally, a cell can only divide if it
has correctly shared out all its genes, ensuring each new cell receives a
complete set. If there is a problem with the process of sharing out genes, an
alarm will be triggered and the cell will not divide. Drugs like Taxol work by
attacking the system responsible for sharing out genes and so triggering the
alarm, sending cancer cells to their deaths.
But in the study, cells with high
amounts of AURORA-A seemed to override the alarm and continue to divide, even
when their genes were not correctly shared out. This ability to ignore the alarm
could make them resistant to Taxol-type drugs.
Sir Paul Nurse, Chief Executive of
Cancer Research UK, noted: "This study gives us a better understanding of
the molecular basis of drug resistance and opens up real opportunities for
overcoming the problem.
"Taxol is a valuable drug for
many patients with late-stage cancer, so finding ways of improving its
effectiveness would be an important development."
Cancer Research UK (http://www.cancerresearchuk.org)
Cell, January 2003