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Possible expansion of application area for cancer drug

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(22-06-2018, APA) - Around 1.6 million people die of lung cancer every year worldwide. For the treatment of advanced non-small cell lung cancer, “targeted therapy” with drugs was developed years ago that act on certain gene mutations. According to a Viennese cancer researcher, one of the drugs – afatinib – could expand its field of application. Herwig Moll, Emilio Casanova and their co-authors from the Ludwig Boltzmann Institute of Cancer Research and MedUni Vienna have now published a study in “Science Translational Medicine”. This work is done on mouse models.

The concept of “targeted therapy” was introduced into oncology years ago. Ultimately, this involves the (also genetic) analysis of tissue samples. The pharmaceutical industry has developed drugs that specifically block the growth of tumour cells when they have certain genetic mutations that make the disease more aggressive. One example of this is non-small cell lung carcinoma, which has a mutation in the receptor for the epidermal growth factor (EGFR). Such first-generation substances (erlotinib, gefitinib) have temporarily achieved good treatment success for some of the patients: In Austria, for example, around 13 percent of patients with a non-small cell lung carcinoma with EGFR mutation are affected.

However, significantly more patients have a mutation in the KRAS gene of the tumour cells. Depending on the study, the proportion is between 20 and 30 percent. However, since no drugs have been available to influence this, lung cancer patients have not yet been tested for such mutations. In the treatment of lung carcinomas with EGFR mutations, on the other hand, active substances of newer generations (e.g. afatinib, osimertinib) have been developed against which tumour cells can develop less resistance. Afatinib not only restrains EGF receptors (EGFR) but also inhibits the structurally related ErB2, ErB3 and ErB4 receptors on tumour cells.

Until now, the dogma was that the use of EGFR inhibitors in a mutation in the KRAS gene of tumour cells was ineffective and not sensible. This is exactly what the Viennese scientists are questioning with their new work with mouse models. It appears that complete blocking of EGFR and related ErB receptors (2, 3 and 4) also interferes with the KRAS signalling pathway. Mice showed slower growth of tumour cells and there was significantly longer survival of the animals.

The findings could speak in favour of clinical studies for patients with lung cancer and KRAS mutations using afatinib or other agents that block the four receptors. “We are pleased with the conclusion of our experiments: that afatinib can obviously be a rational therapy for a large number of lung cancer patients,” said Casanova. However, the principle can only be widely applied when positive results from clinical studies with patients are available. In this case, the field of application of such drugs could possibly be expanded.