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Proteins help identify patients who will respond better to different treatments in certain cancers

American Association For Cancer Research (AACR) : 19 November, 2003  (Company News)
Scientists today presented studies of proteomic and genomic markers that could help oncologists devise better treatment approaches for specific patients, and may improve clinical outcomes. The studies were presented here today at the International Conference on Molecular Targets and Cancer Therapeutics organized by the American Association for Cancer Research, National Cancer Institute and European Organisation for Research and Treatment of Cancer.
Molecular marker expression phenotype is an independent prognostic factor for outcome in the chart head and neck cancer randomized trial: Abstract 733

A major clinical study of head and neck cancer patients found that molecular markers, the proteins that distinguish specific tumors, allowed doctors to identify patients who would respond better to radiotherapy than others. Investigators looked at molecular marker expression profiles in 402 patients with head and neck squamous cell carcinoma. The study focused on biological factors such as vascular density and the expression of proteins involved in the regulation of cell cycle progression, proliferation, or apoptosis (programmed cell death), which are known to affect the way that a tumor responds to radiotherapy.

'We are using new strategies for data analysis to exploit the potential of molecular markers,' said Francesca Buffa, PhD, of the Gray Cancer Institute in London. 'We hope that by tailoring cancer therapy to the biological behaviour of an individual patient's tumor, we will be able to improve the success of radiotherapy and provide increased clinical benefits to the patients,' she added.

Eight distinct groups of tumors, each with similar biological profiles, were identified within the patient group. Drs. Buffa, Soren Bentzen and their colleagues looked at whether it was possible to predict the outcome of radiotherapy based on these molecular profiles, when compared to more traditional characteristics such as the nodal stage and primary site of the tumor, and the patient's age and gender.

Responses were evaluated in a multivariate analysis of patient survival and time to local treatment failure. Two tumor profiles were identified that had clearly different clinical outcomes. One group of tumours had a better-than-average response to radiotherapy, with a success rate of 67 % percent at five years compared to a 52 percent overall success rate. A second group showed a very poor response to radiotherapy, with a success rate of 37 percent at five years. Furthermore, in a third group of tumors, strongly accelerated radiotherapy provided a significant clinical benefit. In this group a success rate of 66 percent at five years was seen for patients undergoing an accelerated version of radiotherapy, compared with a 33 percent success rate in patients undergoing conventional therapy.

High through-put molecular diagnosis of gliomas using direct-tissue MALDI-MS analysis: Abstract 1023

The 'molecular fingerprint,' or protein patterns, of the most common type of primary brain cancer can be used to classify tumors and predict their aggressiveness, scientists at the National Institutes of Health and Vanderbilt University report.

The researchers used mass spectrometry to develop profiles of proteins active in 60 human brain samples, including 19 normal tissue, 15 grade II, 11 grade III and 15 grade IV gliomas. The researchers identified more than 200 potential molecular markers that distinguished normal from malignant tissue and differentiated grade of tumor. With these protein profiles, they were also able to group tumors, with approximately 90 percent accuracy, according to survival rate (15 biopsies from patients who survived less than one year and 26 from patients who survived more than one year).

'This study is important because we show that the 'molecular fingerprint' of the tumor can be used to assess the progression of disease and more importantly predict how aggressively it will behave,' said Richard Caprioli, Ph.D., Stanley Cohen Professor of Biochemistry at Vanderbilt. 'This is the necessary step before we can get to truly predictive medicine, where we would analyze an individual's tumor, scientifically predict how it will behave and use that information to tailor treatment decisions.'

Each year, about 25,000 new gliomas are diagnosed, about half of which are particularly vicious, with a median survival of one year with aggressive therapy. Currently, diagnostic techniques do not distinguish between more aggressive and less aggressive tumors, which appear identical under the microscope.
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