A study conducted by researchers from the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences has identified the enzyme MTH1 as the “Achilles’ Heel” of malignant tumor cells. The vulnerability could be explored as a potential novel antitumor therapeutic approach.
In addition, researchers have also discovered the chemical mirror image of crizotinib, an existing anti-cancer drug, to be effective at inhibiting MTH1 activity. Findings from the study show that malignant tumor cells are vulnerable to imbalances in nucleotide metabolism. The research was conducted by the researchers from Vienna in collaboration with colleagues from Oxford and Stockholm.
“This paper represents a creative and original application of pharmacology, signal transduction biochemistry, and structural biology employed to make inroads into the therapy of cancers that have to date resisted effective treatment,” said Robert A. Weinberg, founding member of the Whitehead Institute for Biomedical Research, Professor of Biology at MIT in Cambridge, USA.
The researchers were able to demonstrate that MTH1 targeting drugs selectively induce DNA damage in cancer cells. The investigational anti-MTH1 drugs were also able to impair growth of aggressive, difficult to treat human tumors in model systems. MTH1 therefore, presents a therapeutic target that could herald a breakthrough in cancer therapy.
Scientific Director Giulio Superti-Furga, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, said, “The elucidation of the mode of action of drugs is one of the greatest strengths of CeMM, whose expertise and technology assets are world-class in this area. Without the support of public funding for basic research this first breakthrough would not have been possible, and therefore we are grateful to the taxpayers. However, the next challenges will be costly, and it would be a shame if we had to give up at this point in time. Therefore, we depend on a solid funding base and are, in addition, also seeking additional sponsors, philanthropists, organizations, and partners, who share our vision of a fight against diseases through innovative research, and who are interested in a continuation of our research.”
The study was published online by the scientific journal Nature earlier this month.