Cause of tumor resistance to angiogenesis inhibitors identified

Angiogenesis -- the formation of new blood vessels from existing ones -- significantly contributes to tumor growth, since tumors need oxygen and nutrients to progress. Several drugs are aimed at inhibiting angiogenesis. However, the benefit of this specialised cancer treatment does not always last long and certain types of cancer hardly respond to it, if at all. This resistance to angiogenesis inhibitors is a widespread problem in everyday clinical practice.

The scientists involved in the study have now shown that penetration of these angiogenesis inhibitors within the tumor tissue is very variable. This means that only a few cancer cells are reached by an effective concentration of the drug.

In the international study, tumors were treated with five different angiogenesis inhibitors in a mouse model. Using a new imaging process (Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging; MALDI-MSI), the scientists were able to measure the concentration and distribution of the cancer drug in the tumor tissue and correlate them with the drug's efficacy.

Lead investigator Balazs Döme, Head of the Translational Thoracic Oncology programme at the Division of Thoracic Surgery at the Medical University of Vienna, says: "Previous research into the mechanisms of resistance to angiogenesis inhibitors predominantly focused on molecular factors. By focusing on the inhomogenous and therefore suboptimal distribution of the active agents in the tumor tissue, our team was able to identify an important mechanism that explains why angiogenesis inhibitors are sometimes ineffective in clinical use."

Joint lead investigator György Marko-Varga, Head of the Clinical Protein Research and Imaging research group at the Division of Biomedical Research of Lund University in Sweden adds: "The diminished efficacy of this cancer treatment is also probably due to the fact that it was previously impossible to reliably image the distribution of the drugs in the tumor tissue. Our new method therefore offers cancer researchers and oncologists the opportunity to gain a better understanding of how these drugs behave and how they are distributed in the body and the tumor tissue."

The results of this study, which have been published in the journal Theranostics, should subsequently lead to the development of new treatment strategies to improve the distribution and efficacy of angiogenesis inhibitors in tumor tissue in the future.