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A method of sensitization of cancer cells to EGFR inhibitors
Method allowing to increase sensitivity and/or overcome resistance to EGFR inhibitors in cancer cells through inhibition of palmitoyltransferase DHHC20.
Inappropriate activation of the epidermal growth factor receptor (EGFR) contributes to a variety of human malignancies and correlates with poor prognosis and resistance to therapy. Whereas therapy targeting EGFR is currently approved for non-small cell lung carcinomas (NSCLC), advanced colorectal cancer, glioma, pancreatic carcinoma and head and neck tumors; triple negative breast cancer and NSCLC often show resistance to currently available therapies.
Dr. Eric Witze’s lab at Penn has found that inhibition of palmitoyltransferase DHHC20 in cancer cells creates a dependence on EGFR signaling for cancer cell survival. Using a palmitoyltransferase inhibitor researchers demonstrated increased sensitivity to Gefitinib in EGFR-activated cancer cells as well as reversal of insensitivity to Gefitinib in lung cancer cells.
Sensitization of drug-resistant cancers
Potential reduction of the treatment doses and side-effects
Potential use in recurrent cancer patients
Combinational therapy combining EGFR inhibitors and DHHC20 inhibitors
Stage of Development:
In vitro data
Docket # 16-7601
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Associate Director, PSOM Licensing Group
University of Pennsylvania
Therapeutics & Vaccines
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