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Does the genotype have an effect on EGF-R inhibitors?

Researchers at the University Hospital in Ulm are investigating whether patients’ genotypes interfere with the effect and tolerability of specific cancer medicaments. In a project, which is funded by the Wilhelm Sander Foundation with a total of 90,000 euros, the pharmacologist Julia Kirchheiner and the oncologist Thomas Seufferlein are investigating the pharmacogenetic importance of those drugs that inhibit the epidermal growth factor receptor (EGF-R). These drugs are used to inhibit the growth of tumours in targeted cancer therapies.

Cancer patients treated with inhibitors such as cetuximab, erlotinib, gefitinib or panitumumab usually suffer from large areas of skin rush and pimples during the first weeks of treatment. The strength of the skin’s reaction to the drugs cannot be anticipated and differs from patient to patient.

The degree of skin toxicity is directly related to the effectiveness of the drug

Undesired side effects of cancer drugs. (Photo: Work group Kirchheiner)
The undesired side effects of anti-cancer drugs, however, provide important information on the efficiency of cancer therapies. There is evidence that genetic variability in drug metabolising enzymes and drug targets influences the drug response and hence affects the treatment outcome. Studies have shown that EGF-R inhibitors had a much stronger effect in patients who developed skin alterations such as scurf, rash or pimples. The studies also showed that patients who received high inhibitor doses up until the time of the development of a skin rash, responded far better to the therapy than those patients who did not show any skin redness.

The project of the researchers from Ulm involves the investigation of 400 patients who are treated with EGF-R inhibitors. The researchers hope to identify the genetic factors that result in a more or less strong skin reaction. In addition, the researchers will use cell cultures from the skin samples of healthy volunteers with different genotypes in order to see how these variants affect cell signal transmission.

Learning to assess patients’ reactions

The project’s goal is to gain a better understanding of the functional importance of the variability in genes that affect the inhibition of EGF-R, in turn providing insights into how patients might respond to a certain EGF-R inhibitor. This might help in the selection of a drug dose that is best suited to the individual patient and to choose different therapeutic strategies for patients who have a pharmacogenetic profile that suggests a weaker drug effect.

Source: Wilhelm Sander Foundation - 13 August 2008, (P, wp 20 August 2008)
Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/does-the-genotype-have-an-effect-on-egf-r-inhibitors