Colon cancer: ASA on everyone’s lips

2. December 2013

Already for 45 years there has been evidence that acetylsalicylic acid can help in the battle against colon cancer. Which cancer patients appear to benefit from small, daily doses of aspirin has now been discovered by scientists.

At the European Cancer Congress, which ran from 27 September to 1 October in Amsterdam, scientists reported on why aspirin can clearly help some patients with colon cancer to survive for longer but not others. A surface protein on the malignant cells probably plays a crucial role here. The scientists point to HLA class 1 (Human Leukocyte Antigen class I), a cell surface protein which is produced by a number of genes, all of which are involved in the maintenance of the immune system.

Platelets camouflage cancer cells

Dr. Marlies Reimers of the University of Leiden in the Netherlands explained the background: “We suspect that platelets are involved in spreading cancer through the body. They virtually shield the cancer cells in the blood away from the immune system, such that the cells are able to settle in other organs undetected. ASA could be helping in unmasking these tumour cells by affecting platelet formation. Then the immune system can again recognise and eliminate the tumour cells”.

Retrospective study

Dr. Reimers and her colleagues as part of a retrospective study presented studies of patients who after their cancer diagnosis took ASA, were registered between 1998 and 2007 in the Eindhoven Cancer Index and were more than 70 years of age. They examined in 999 cases the extent to which the receptor surface of HLA-1 and the enzyme COX-2 were present in the patients. In addition, the researchers isolated DNA from 663 tumours, in order to investigate mutations in gene PIK3CA because both the presence of the enzyme COX-2, as well as mutations in the PIK3CA gene, have been implicated in the pathogenesis of colon cancer. It is also known that ASA inhibits the functioning of enzyme COX-2, which is present in about 70% of all colon tumours.

Surface protein HLA-1 obviously crucial

The evaluations of scientists showed that only those patients whose tumours carried HLA-1 on their surface benefited by taking low doses of aspirin (80 mg per day). If these patients took ASA, their probability of dying during the following four years decreased by half – compared with patients whose tumour cells also expressed HLA-1 but who took no ASA. In patients who had expressed no HLA-1 this effect did not occur. “HLA-1 might therefore become used as a biomarker, by which it can be determined which patients can benefit from the ASA intake after being given a cancer diagnosis”, says Dr. Reimers. “Our results also show that the presence of COX-2 and mutations in the PIK3CA gene are apparently not linked to ASA therapy”. Since then we had assumed exactly the opposite.

ASA: Preventative against colon polyps

However patients with a high COX-2 expression had no survival advantage over patients with low COX-2 presence. From this Dr. Reimers and her colleagues conclude that ASA acts in two different ways against colon cancer: on the one hand preventatively, on the other hand via the control of metastases. Reimers adds: “The first route runs via PIK3CA mutations and COX-2 expression. This path seems to be of importance in the prevention of colon cancer. Inheritance studies have shown that ASA can help to prevent the onset of colon cancer by reducing the formation of polyps in the intestine. Polyps are often the precursor of cancer and their formation has been associated with mutations in PIK3CA and the expression of COX-2”.

A look at the side effects of ASA

The second path has to do with the metastasis process and is causally linked to platelets, according to Reimers. “At the moment it’s still pure speculation, but it could well be that the interaction of platelets with HLA-positive tumour cells that circulate in the blood increases the metastatic potential of cancer cells. ASA disrupts this interaction and thereby prevents the formation of metastases which ultimately lead to death of the patient”. Scientists working under Dr. Reimers refer to further studies that could potentially support their findings. In the UK and Asia, a multicentre, randomised phase III study (ASCOLT Study) is running, which is already examining the effect of aspirin on patients with colon cancer. Despite all the hype it’s worth taking a look at the side effects of ASA. Shih-Wei Lai of the School of Medicine at the China Medical University in Taichung, Taiwan, emphasised in his comment on the study moreover that the risk of bleeding being caused by ASA should always be weighed against the potential benefits of the drug in colon cancer.

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