Professor Andrew Szczeklik from Poland and Professor Graeme Hankey from Western Australia will present the latest findings on aspirin resistance at the XXth Congress of the International Society of Thrombosis and Haemostasis today.

"There are at least two possible explanations for the aspirin-resistance phenomenon," said Professor Szczeklik. "One is high levels of blood cholesterol, which can in itself promote coagulation events in the blood stream. In patients with high cholesterol levels, aspirin in in normal doses has hardly any anti-clotting effects, whereas treatment with a statin (inhibitor of cholesterol) significantly reduces blood clotting. In patients with coronary heart disease, aspirin exerts it anti-coagulant effects only when blood cholesterol is in the 'normal' range."

Szczeklik went onto say, "A patients genetic make-up may alter their response to aspirin resistance.. For example, in coronary heart disease patients carrying one particular gene are resistant to the anti-coagulant action of aspirin and are at increased risk of an acute coronary event."

Perth researcher, Professor Graeme Hankey, has shown that patients who show evidence of aspirin resistance do respond well to another drug called Clopidogrel.

"Clopidogrel had anti-clotting and anti-inflammatory effects in patients with diseased arteries. These effects were greatest in the aspirin-resistant patients," said Hankey.

"The use of aspirin has risen dramatically in Australia in the late 1990's. This is why it is vital that aspirin resistance is considered when implementing anti-clotting therapy. Present data indicate that this particularly applies to survivors of a heart attack or unstable angina, patients receiving bypass surgery as well as people with high cholesterol," reported Hankey.

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"This tumor model was generated in such a way that it closely mimicked acquired resistance to gefitinib and EMP-1 was identified as a surface biomarker whose expression correlated with the development of resistance to gefitinib," Agus said. "Molecular diagnostics, such as this, are extremely important as we attempt to personalize cancer treatments in the next decade."

To confirm whether or not EMP-1 was present in patients with non small-cell lung cancer who were being treated with gefitinib in clinical trials, the investigators examined tumor samples from 39 patients. They found that none of the patients who responded to treatment with gefitinib expressed EMP-1. Alternatively, EMP-1 was present in 14 patients (28 percent) who had non small-cell lung cancer that had either stabilized or progressed. Importantly, however, one patient who initially did not express EMP-1 and had responded to treatment with gefitinib, later acquired resistance to the drug, and EMP-1 was significantly expressed when the cancer recurred.

"This tells us that the absence of EMP-1 does not completely predict whether a person won't stop responding to gefitinib. However, it appears that testing for the presence of EMP-1 at the outset of treatment may help physicians predict which patients won't benefit from the drug," Jain explained. "Importantly, we found that EMP-1 is not only a marker for patients who won't respond to gefitinib, but also for those who will later develop resistance to the drug."

To confirm that EMP-1 was also present in patients with types of non small-cell lung cancer that do not respond to gefitinib, the investigators examined tumor samples from patients with adenocarcinoma and squamous cell carcinoma. They found that EMP-1 was expressed in 66 percent of the squamous cell carcinomas and 40.9 percent of those with adenocarcinoma, confirming that the presence of EMP-1 is directly linked to Iressa-resistance.

"This is an important new tool in the treatment of lung cancer which needs to be confirmed in ongoing large clinical trials," said Ronald Natale, M.D., an oncologist at the Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute and a principal investigator on clinical trials with gefitinib, including the Iressa Dose Evaluation in Advanced Lung Cancer Trial 2 (IDEAL 2) that provided the basis for the initial approval of Iressa by the FDA.

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