Lung cancer cells use molecular “guards” to protect the mutated EGFR gene and evade the effects of drugs. This conclusion emerged from a study by scientists at the ASTAR Institute of Molecular and Cell Biology (ASTAR IMCB).
Elchi.az reports that the research was published in the journal “Science Advances”.
EGFR mutations cause cells to grow uncontrollably and are found in up to 60 percent of lung adenocarcinoma cases, especially in Southeast Asia. Although targeted drugs are initially effective, almost all patients develop drug resistance over time.
Scientists have investigated why mutant EGFR proteins remain stable and active longer than normal proteins. It was found that cells enrich the environment with ATP — an energy molecule. ATP activates the P2Y2 receptor on the cell surface. This receptor attracts the integrin β1 protein, creating a “protective barrier” around the mutated EGFR. This barrier prevents the protein from falling into the cell’s “recycling center” and prevents its breakdown. As a result, the tumor continues to grow.
High levels of P2Y2 and integrin β1 were detected in tumor tissues of 29 patients with lung cancer.
“We have discovered that cancer cells use molecular ‘guards’ to protect the mutated protein from degradation,” said Dr. Gandi Buopati, co-author of the study.
Blocking this system in laboratory models resulted in almost complete loss of mutant EGFR. In addition, scientists have tested a natural substance found in broccoli and cabbage varieties – kaempferol. Daily treatment of drug-resistant tumors with kaempferol for 24 days significantly reduced their size, but did not affect cells with normal EGFR.
“By affecting P2Y2, we are targeting not only the mutation itself, but also the mechanism that protects its stability,” explained Professor Vanjin Hong.
According to the researchers, this approach can complement existing drugs, help prevent or weaken drug resistance, and open new opportunities for the treatment of lung cancer.
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