Researchers at Vanderbilt University Medical Center, Nashville, and Massachusetts General Hospital Cancer Center, Charlestown are offering new insights into the mechanisms of tumor
The mechanism behind tumor resistance to a drug known as gefitinib may have been unraveled by researchers at Vanderbilt University Medical Center, Nashville, and Massachusetts General Hospital Cancer Center, Charlestown.
It is known that drugs targeting EGFR effectively treat certain types of cancer, including breast cancer, but despite initial success of the treatment, the tumor recurs in many patients and is resistant to the effects of the drug.The authors of the study said that these observations would explain why tumors become resistant to the effects of EGFR-targeted drugs. This information is essential if more effective therapies are to be developed.
Led by Carlos Arteaga and Jeffrey Engelman, the researchers generated cancer cells resistant to the effects of gefitinib and found that these cells were constantly sending signals from a protein on their surface known as IGF1R.
This indicated that two proteins known as IRS-1 and PI3K were always linked and if in case this association was disrupted, the cells once again became susceptible to the effects of gefitinib.
By researching further, the scientists showed that if mice with a human tumor were treated with gefitinib and a drug inhibiting IGF1R their tumors did not recur, whereas neither drug alone could prevent tumor recurrence.
Thus they recommended that drug combinations that target both EGFR and IGF1R might prove to be beneficial to individuals with cancers that are responsive to EGFR-targeted therapies.
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