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Gene activity pattern could help select colorectal cancer treatments

French scientists have identified a pattern of gene activity that accurately predicts which colorectal cancer patients will respond best to which treatments. The findings could be used in future to develop a test to determine rapidly which drugs a patient should receive. The ...

French scientists have identified a pattern of gene activity that accurately predicts which colorectal cancer patients will respond best to which treatments. The findings could be used in future to develop a test to determine rapidly which drugs a patient should receive. The French team is the first to demonstrate the use of gene profiling in predicting responses to treatment in colorectal cancer patients. The findings were presented at the 20th Symposium on Molecular Targets and Cancer Therapeutics in Geneva, Switzerland on 22 October. If caught in the early stages, colorectal cancer can usually be treated successfully by surgery. However, in about half of all colorectal cancer patients the disease spreads to the liver, and these cases are much harder to treat. Usually, the first line of attack in these patients is a chemotherapy regime such as FOLFIRI, which comprises the drugs leucovorin, fluorouracil and irinotecan. Yet despite the arrival on the scene of new and better drugs, these regimes are ineffective in around half of all patients. Furthermore, even those tumours that initially respond well to treatment tend to become resistant to the drugs over time. Currently, there is no way to predict which patients will respond to the first-line treatments and which would do better with alternative treatment regimes. 'It is critical for the success of overall treatment to choose a chemotherapy regime that is most likely to induce a maximal response during the first course of treatment,' says Dr Maguy Del Rio of the Montpellier Cancer Research Institute in France. 'It is a major clinical challenge to identify a subset of patients who could benefit from a particular chemotherapy, and to identify those who will not and therefore need to be treated using an alternative treatment.' In this latest study, Dr Del Rio and her team studied the activity levels of a number of genes in samples taken from 19 patients with colon cancer that had spread to the liver. None of the patients had started on chemotherapy at the time of the trial. They identified a genetic 'signature' involving 11 genes that clearly identify which patients will respond well to treatment with FOLFIRI and which will not. On the basis of these results, the scientists developed a mathematical model that was able to classify the patients into the right group 100% of the time. 'The fact that we achieved 100% accuracy could be due to our small sample size of 19 patients,' admits Dr Del Rio. 'Obviously it is essential to validate and, if necessary, to improve the gene signature in a larger independent cohort of patients. Until it is properly validated, the gene signature cannot be used in the clinic.' However, once validated the findings could be turned into a test which could identify which patients will respond best to the most common treatments and which patients would benefit from different drugs. Patients identified as non-responders could be treated immediately with alternative regimes and newer, more advanced drugs. 'For patients with metastatic colorectal cancer, time is an important factor and to make a good first-line treatment choice could be decisive in the overall success of the treatment,' commented Dr Del Rio. According to figures from the International Agency for Research on Cancer, a part of the World Health Organization, there were around 300,000 cases of colorectal cancer in the EU in 2006, making it the third most common type of cancer behind breast and prostate cancer. In the same year, around 140,000 people died of the disease. Worldwide, some 945,000 new cases are diagnosed every year.

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