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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. 

Problem:

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.

Solution:

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.

Advantages:

  • Sensitization of drug-resistant cancers
  • Potential reduction of the treatment doses and side-effects
  • Potential use in recurrent cancer patients

Applications:

Combinational therapy combining EGFR inhibitors and DHHC20 inhibitors

Stage of Development:

In vitro data

Desired Partnerships:

  • Collaboration
  • Co-development
  • Drug discovery

Patent Information:

Inventors:

Docket # 16-7601

For Information, Contact:

Linara Axanova Associate Director, PSOM Licensing Group
University of Pennsylvania
axanova@upenn.edu

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