According to the study's authors, around 40% of lung cancer patients are resistant to a specific targeted therapy drug known as erlotinib. The drug is an EGFR inhibitor and the therapy is meant to block non-small cell lung carcinoma tumors from growing.
The new study, published in the Journal of Clinical Investigation, showed that the over-expression of the Cripto-1 protein in patients could be what is making them resistant to the drug. Researchers demonstrated that blocking Cripto-1 signaling transduction in animals restored the ability of erlotinib to act on lung cancer cells. This blocking was accomplished using an Src inhibitor.
"This is a welcome finding because Cripto-1 belongs to a family of proteins that can be targeted by drugs that have already been developed," Dr. Giuseppe Giaccone, senior investigator on the study and an associate director for clinical research at Georgetown University's Lombardi Comprehensive Cancer Center. "Most patients using erlotinib exhibit either intrinsic or acquired resistance, so we frankly don't cure anyone with the drug, although we can extend lifespan. So if we can understand what is limiting the activity of the drug up front, I believe treatment of patients can be vastly improved."
Giaccone and his colleagues are currently setting up a clinical trial to test the method on human lung cancer patients. Though the specific Src inhibitor used in the study is no longer an option, the researchers say they will use the Src inhibitor AZD0424 in combination with erlotinib during the trial. Patients selected for the trial will have non-small cell lung cancer and have cancer cells with an EGFR mutation. Previous research has found these types of patients to be most sensitive to erlotinib.
"There has been very little investigation when a person never responds to an EGFR inhibitor - most research has been done on acquired resistance that occurs after the drug has shown some benefit," said Giaccone.
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