HomeNerviano Researchers’ Contribution in Building Anticancer Drug Actions Atlas

Nerviano Researchers’ Contribution in Building Anticancer Drug Actions Atlas

Nerviano, Italy, 05.04.2018

New data are now available to support Research and Innovation in oncology. This is the most complete study carried out, up to date, on kinases and over 240 inhibitors and it illustrates how new opportunities for cancer treatment could arise from some kinase inhibitors already approved or currently in clinical development phase.

The study is a multi-center project that has involved four experienced researchers from Nerviano Campus, highly regarded in the field of kinase biochemistry and structural chemistry – area in which the Center has developed a leading expertise through the development of a dedicated Kinase Platform.

Coordinated by the Technical University of Munich and now published in Science, the study is a complete analysis of 243 kinase inhibitors, drugs that block enzymes involved in all tumor transformations. The international team of scientists, IT specialists and doctors has developed a unique approach in order to identify which kinases and which interactions within tumor cells are specifically involved in the inhibitors’ activity, regardless of their current pharmacological indication. The purpose was to create an atlas to support research and development of new cancer drugs and to find new applications for already approved treatments.

In addition, the study is also the largest comparative study of anticancer molecules in different pathological contexts, positioned much closer to cancer biology than traditional biochemical analyses because it considers patients tumor tissues in addition to cell lines. Scientists analyzed the entire cellular content of leukemias, brain, lung and colon cancers in response to inhibitors, systematically mapping the drugs‘ spectrum of binding partners, while the pathophysiological cellular context.

The contribution of Nerviano Researchers is focused on the comprehensive structural characterization of various MELK inhibitors binding their target protein, an extension of Nerviano’s pioneering crystallography work (resolving the first crystallographic structure of MELK, published  in 2013).

Lasting several years, this study produced a vast atlas of drug actions, a unique data and analysis resource available to scientists, researchers and clinical oncologists through the databases of ProteomicsDB and the Cancer Proteome Analysis Platform (DKTK German Cancer Consortium), where they can deduce the interaction profiles between a drug and its pharmacological targets, as well as new collateral inhibitory activities to be investigated. This large volume of data, a huge source of reading and interpretation, illustrates how the information may be used in basic research, drug discovery, or clinical decision-making.


References & Editorials

‘The target landscape of clinical kinase drugs’, S. Klaeger et al., Science 358, 1148 (2017)

‘The Landscape of Kinase Inhibitors’,  By Derek Lowe, January 16, 2018