New drugs could also be deployed against lung and pancreatic cancers


A new anti-cancer drug may be effective against a wider range of cancers. Using a mouse model and samples taken from cancer patients, a team from the Technical University of Munich (TUM) has shown that a new class of drugs known as SHP2 inhibitors is hard-to-treat tumours such as lung and pancreatic cancers. The major role of this SHP2 inhibitors is that Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases Clinical trials currently underway had previously excluded patients with these cancers.


Lung and pancreatic cancer are referred to as KRAS tumors, as they allowed the same genetic error. This error means that the KRAS protein, involved in, among other things, cell division, no longer works properly and is always active. As a result, the cells divide out of control, leading to tumor formation. KRAS tumors make up about a third of all tumors in humans. The problem, however, is that the KRAS protein is also active and plays a crucial role in healthy cells, so that simply deactivating it with drugs is not an option.



SHP2 protein is essential for tumor growth

One strand of their work involves mice with a defective KRAS protein. When the team additionally removed the SHP2 protein from the mice, they no longer developed tumors. With these results, the research team was able to prove that SHP2 is essential for tumor formation and that SHP2 might also be a key drug target in aggressive KRAS tumors. The results were confirmed when they used recently developed SHP2 inhibitors in their mouse model. When the mice were given an SHP2 inhibitor, existing tumors grew more slowly and were easier to control.

Combination therapy helps fight resistance
The results could also solve another problem which arises when treating KRAS tumor: they frequently develop drug resistance. The team tested the new drug in combination with MEK inhibitors, a class of drugs which are already used therapeutically. "These drugs are effective, but many patients quickly develop resistant cancer cells," explained by Katrin Ciecielski, co-author of the paper. The study found that the new SHP2 inhibitors cause resistant cancer cells to revert to being susceptible to the old MEK inhibitors. A combination of these two drugs could therefore offer a new approach for treating drug-resistant tumors, suggests Hana Algül.

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