Technology Listings


Combination Therapy for the Treatment of Lung, Head, and Neck Cancers

Application

Combination of niclosamide and erlotinib to treat lung, head, and neck cancers as well as overcome resistance to alternative treatments.

Key Benefits
  • Anti-cancer treatment combines two existing and approved therapeutics.
  • Effective cancer treatment for erlotinib resistant patients.
Market Summary

Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective anti-cancer agents, a recent emergence of resistance to these therapies is a major clinical problem. The majority of patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC) show an initial response to these inhibitors but after approximately a year, resistance develops and efficacy decreases significantly.

Technical Summary

EGFR tyrosine kinase inhibitors such as erlotinib and gefitinib, are effective treatments for NSCLC; however these therapies lose efficacy over time. Emory researchers have found that erlotinib enhances phosphorylation of STAT3, a transcription factor that mediates the expression of a variety of genes in response to cell stimuli and plays a role in cell growth and apoptosis. This STAT3 phosphorylation increases STAT3 activation which leads to elevated levels of Bcl2/Bcl-XL, a survival signal linked to cancer, at both the mRNA and protein level, and the consequent loss of erlotinib sensitivity. To address this sensitivity loss, a potent STAT3 inhibitor, niclosamide, can be used in combination with erlotinib to block STAT3 phosphorylation and the resulting transcriptional activity. In this way, niclosamide would block erlotinib-induced activation of the STAT3/Bcl2/Bcl-XL survival pathway in lung cancer cells and lead to the reversal of erlotinib resistance in vitro and in vivo.

Developmental Stage
  • In vitro treatment of cells with niclosamide blocks erlotinib-induced activation of STAT3/Bcl2/Bcl-XL and reverses erlotinib resistance.
  • Combination treatment of erlotinib and niclosamide overcomes acquired erlotinib resistance in vivo in a xenograft mouse model of cancer.
Patent Information
Tech ID: 13192
Published: 12/10/2014
Category
Therapeutics

Contact
Hyeon (Sean) Kim
Licensing Associate
Emory University
hkim70@emory.edu

Inventor(s)
Xingming Deng
Rui Li
Fadlo Khuri
Taofeek Owonikoko

Keywords
Biologic
Oncology
Repurposed Drug
Small Molecule