Anticancer drug nintedanib found to be effective against malignant pleural mesothelioma

Researchers in Europe have found that the multi-target small molecule anticancer drug nintedanib shows promising effectiveness in halting the growth of human malignant pleural mesothelioma – a fatal thoracic tumour – in preclinical models.

Malignant pleural mesothelioma is a particularly aggressive tumour that occurs in the lining that covers the lungs. It typically results from exposure to asbestos. Standard anti-mesothelioma treatment includes surgery, chemotherapy, irradiation or multimodal therapy – a combination of these approaches. As these therapies have reached an efficacy plateau, new targeted approaches are needed to improve survival.

However, despite proven efficacy of molecularly targeted drugs across a wide spectrum of other cancer types, most mesothelioma patients have failed to benefit from this novel treatment paradigm. New research, however, suggests that by preventing the growth of new mesothelioma blood vessels, which starves tumours of nutrients and oxygen, the novel targeted medication nintedanib represents a promising candidate for helping patients with mesothelioma.

Commenting on the research, first author Viktoria Laszlo from the Division of Thoracic Surgery at the Medical University of Vienna, Austria, said: "Nintedanib, an inhibitor of molecules responsible for promoting mesothelioma growth and new tumour blood capillary development, is already approved for other fatal thoracic diseases such as idiopathic pulmonary fibrosis and lung adenocarcinoma.

Now we demonstrated, for the first time, that human mesothelioma cells express the target molecules of nintedanib and, furthermore, that this drug inhibits the growth and migration of mesothelioma cells."

"Moreover, we showed that nintedanib potently reduces the growth and vascularisation of human mesothelioma tumours implanted into the thoracic cavity of mice."

Study leaders Balazs Döme, Head of the Translational Thoracic Oncology Program at the Medical University of Vienna, Austria and Balazs Hegedus, Department of Thoracic Surgery, University Medicine Essen – Ruhrlandklinik, Germany, added: "Importantly, this antitumour effect of nintedanib in experimental animals was stronger than that of bevacizumab – the reference blood vessel growth (angiogenesis) inhibitor in clinical oncology – in the treatment of less vascularised mesotheliomas. A key message of these animal experiments is thus that nintedanib might be considered superior to bevacizumab as part of systemic anti-tumour therapy for patients with less ‘angiogenic’ mesotheliomas."

The study  is of clinical relevance as – together with the promising results of the LUME-Meso clinical trials evaluating nintedanib in combination with cisplatin-pemetrexed chemotherapy in mesothelioma patients – it might help nintedanib to become an integral part of the standard-of-care for patients with mesothelioma.

The study was published in the journal Clinical Cancer Research and the work was supported by the Boehringer Ingelheim RCV GmbH, Vienna, Austria.

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