Office of Technology Transfer – University of Michigan

Small Molecule Inhibitors of ESC-Mediated Transcription

Technology #5129

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Researchers
Anna K. Mapp
Managed By
Stefan Koehler
Title: Senior Licensing Specialist, Health Technologies 734-764-4290

Targeting EGFR in cancer treatment

In 2010, 1.5 million people were diagnosed with breast cancer. It is the most common cancer and the principle cause of death from cancer in women worldwide. Head and neck cancer worldwide incidence exceeds half a million cases annually. EGFR (epidermal growth factor receptor) family of receptor tyrosine kinase proteins are overexpressed in about 30% of breast cancers and 90% of HNSCC (head and neck squamous cell carcinoma), and their increased expression is correlated with increased metastasis, resistance to chemotherapeutic agents, and shorter life expectancy. Although both monoclonal antibodies and small molecule TKIs (tyrosine kinase inhibitors) targeting EGFRs have been approved for treatment of cancer, there is still significant unmet clinical need for more efficacious therapies as TKIs do not fully inhibit activity of their targets at physiological doses and thus lead to activation of alternative receptors that lead to resistance development.

Small molecule ESX-Med23 inhibitor as a cancer treatment

Researchers at the University of Michigan developed a targeted cancer therapeutic that reduces expression of EGFR and ErbB2/Her2 receptors in breast and HNSCC cancer cells lines. A member of the ETS transcription factor family, ESX, interacts with transcriptional co-activator Med23 and activates transcription of EGFR and Her2 tyrosine kinases. Researchers designed a small molecule that effectively inhibits ESX*Med23 protein-protein interaction and inhibits cancer cell proliferation via reduction in EGFR expression. The compound shows positive synergy when combined with TKIs gefitinib and lapatinib and a non-specific HSP90 chaperone inhibitor geldanamycin. In addition to synergistic effects of the compound, it also increases selectivity of both TKIs and geldanamycin for cancer cells, thus lowering toxicity of individual agents when used in combination. Thus, ESX*Med23 interaction inhibitor shows great potential as a cancer therapeutic either alone or in combination with other currently approved therapies.

Applications and Advantages

Applications

  • New compound for treatment of EGFR+ tumors
  • New target validated for use in breast and HNSCC cancers

Advantages

  • New therapeutic target and small molecule inhibitor of this target
  • Shows efficacy alone and synergy when combined with approved drugs