(Vienna, 17th December 2014) A team of researchers from the MedUni Vienna has demonstrated for the first time that inhibiting a specific growth factor (FGF) in pleural cancer can reduce the tumour's aggressiveness and at the same time improve the effectiveness of concomitant chemo- or radiotherapy. This could represent a new approach to treatment.
Malignant pleural mesothelioma is an aggressive form of cancer of the pleura that is caused in many cases by contact with asbestos. In light of the increase in the number of new cases diagnosed, the limited treatment options available and the fact that this type of tumour is often resistant to chemotherapy and radiotherapy, a search for new forms of treatment is urgently needed.
The development and progression of tumours are determined by cell proliferation, migration to other parts of the body and cell death. Fibroblast growth factors (FGFs) and their receptors form part of a signalling system that controls these functions. If the control of these signals is faulty, cancer can develop. FGF receptors are therefore regarded as important interfaces for the development and progression of cancer, but also as potential points of attack for new types of treatment.
Alireza Hoda from the Clinical Department of Thoracic Surgery within the University Department of Surgery at the MedUni Vienna and Vienna General Hospital, a member of the Comprehensive Cancer Center (CCC) Vienna, and Karin Schelch from the Institute for Cancer Research (IKF) at the MedUni Vienna, also a member of the CCC, have for the first time demonstrated the crucial role of FCF receptors in pleural mesothelioma in their most recent work.
New approach to treatment determined
The interdisciplinary team of researchers was able to demonstrate over-expression, i.e. a massively increased presence, of the FGF receptor FGFR1 and growth factors (ligands) FGF2 and FGF18. It was also possible to confirm that stimulation with FGF2 leads to increased cell growth and an increase in cell migration and invasion. By contrast, if FGFR1 is blocked, there is a significant reduction in the tumour cells' survival period and ability to migrate. Comparable results were achieved with an alternative strategy: the expression of a dominant-negative FGFR1 in tumour cells.
Significantly less tumour growth was also observed in the mouse model both with the inhibitor and with the dominant-negative FGFR1. If, during the treatment of tumour cells, FGFR1 inhibition was combined with chemotherapy (with cisplatin) or radiotherapy, there was even an increase in the individual treatment effects.
The project was led by Michael Grusch, IKF, and carried out within the IKF and at the Medical University's Anna Spiegel Center for Translational Research.
Service: American Journal of Respiratory and Critical Care Medicine (AJRCCM) “Fibroblast Growth Factor Receptor Inhibition Is Active against Mesothelioma and Synergizes with Radio- and Chemotherapy”. Karin Schelch, Mir A. Hoda, Thomas Klikovits, Julia Münzker, Bahil Ghanim, Christina Wagner,Tamas Garay, Viktoria Laszlo, Ulrike Setinek, Balazs Dome, Martin Filipits, Christine Pirker, Petra Heffeter, Edgar Selzer, Jozsef Tovari, Szilvia Torok, Istvan Kenessey, Klaus Holzmann, Bettina Grasl-Kraupp, Brigitte Marian, Walter Klepetko, Walter Berger, Balazs Hegedus, and Michael Grusch Am J Respir Crit Care Med. 2014 Oct 1;190(7):763-72. doi: 10.1164/rccm.201404-0658OC.