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Researchers from the Technical University of Munich have recently announced a new type of treatment that targets drug-resistant tumors. They are testing a new class of drugs, known as SHP2 inhibitors, to treat KRAS tumors. KRAS is a gene that makes the protein SHP2. This KRAS protein plays a part in cell signaling pathways that control cell growth, cell maturation, and cell death. A mutated KRAS gene triggers the KRAS protein to become overly active. Cells with this protein will divide uncontrollably, which leads to tumor formation. The SHP2 inhibitor could potentially help save the lives of patients with pancreatic and lung cancers. Both these cancer types are classified as KRAS tumors.

Current Outlook for Lung and Pancreatic Cancers

According to the American Lung Association, the lung cancer five-year survival rate of 17.7% is lower than many other cancer sites. More than half of patients die within one year of being diagnosed because of drug-resistent tumors. The outlook for people with pancreatic cancer varies depending on the stage of the cancer and whether the patient has undergone surgery. Patients diagnosed earlier and have undergone surgery had a five-year survival rates of up to 60%.

Kathrin Ciecielski and Professor Hana Algül (right) discuss the results of the study. Credit: Andreas Heddergott / Technical University of Munich
Will researchers Kathrin Ciecielski, Professor Hana Algül, Alexandra Berninger and Dr. Lesina Marina from the Technical University of Munich (TUM) succeed in hunting down drug-resistant tumors?

Previously, clinical trials for the development of anti-cancer drugs did not include lung and pancreatic cancers. The genetic error that both these cancer types shared is the hyperactive protein. Neutralizing this hyperactive protein with drugs failed to work and deactivating the SHP2 protein is not a feasible option. The KRAS protein is also essential for the other healthy cells to function.

Professor Hana Algül, a Professor of Tumor Metabolism and Head of Gastrointestinal Oncology at Medizinische Klinik II at University Hospital rechts der Isar, shared:

It had previously been thought that the KRAS mutation exerted such severe effects that using other avenues of attack would be doomed to failure.

With the recently developed SHP2 inhibitor, researchers  found another way to win over these drug-resistant tumors.

How Does This New Drug-Resistant Tumors Drug Work?

The treatment plan has a two-pronged mission: remove the rogue protein and introduce the inhibiting drug. The Technical University of Munich (TUM) research team removed the SHP2 protein in one of their model mice. The mice then no longer developed tumors. The research presented more promise as the existing tumors grew more slowly and became easier to control when they introduced the recently developed SHP2 inhibitor.

Potentially, the results of this drug-resistant tumors research can help another issue when dealing with KRAS tumors, that is, the cancer cells becoming resistant to drugs. Katrin Ciecielski, co-researcher of the SHP2 inhibitor study, explains that a class of drugs called MEK inhibitors are available for therapeutic use. Ciecielski shares, “These drugs are effective, but many patients quickly develop resistant cancer cells.”

Hence, the TUM research team tested the SHP2 inhibitor drugs in combination with MEK inhibitors. They found that SHP2 inhibitors can revert MEK inhibitor-resistant cells back to its receptive state. This is another example of how precision medicine is re-shaping medicine and attacking drug-resistant tumors.

The newly developed SHP2 inhibitor drug is showing a lot of promise. Further tests and clinical trials are already underway. Researchers combining SHP2 and MEK inhibitors, with the mission of hunting down drug-resistant tumors, are making bold impacts in improving the lives of patients with KRAS tumors.

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