Developing A novel target therapy for exon-20 EGFR mutated Lung Cancer

Introduction:

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), are used to treat a variety of cancers including non-small cell lung carcinoma (NSCLC). Lung cancer is the leading cause of death worldwide, with more than 1.7 million deaths annually. Response to TKIs in lung cancer can be subdivided into two groups. The first group includes patients carrying sensitizing EGFR mutations in their tumors and TKIs treatment can initially be very successful. Unfortunately, these patients will develop resistance within 10 to 14 months of treatment. The second group of patients accounting for approximately 10% of all cases of EGFR mutations (Yasuda et al., 2013) or 30,000 cases/year, presents primary mutations in EGFR that do not respond to treatment with TKIs. Most of these patients have primary in-frame insertion resistance mutations to TKIs in exon 20 of EGFR. As of today there are no approved treatment for this group of patients, representing a very strong unmet need. Our goal is to develop a treatment to patients carrying EGFR TKI-insensitive exon 20 mutations.

The Technology:

The structure of EGFR has been vastly published, with over 100 available structures, including the common exon 20 EGFR-insertion D770_N771insNPG. Using molecular dynamics simulations and quantum mechanical methods, small molecules (NCE) and cyclic-peptides will be employed to achieve our goal of designing novel molecules for inhibiting the tyrosine kinase domain of exon 20 mutated EGFR. Additionally, will be tested alternative technologies for inhibiting exon 20 EGFR mutated protein such as antisense which directly targeted the mutations.

Advantages:

• There is currently no approved medication for this population.
• Peled is an opinion leader in Lung cancer with a deep understanding of the medical needs, scientific aspects of the technology and access to both patients and biopharma collaborators.

Principle Investigator:

Prof. Nir Peled, MD PhD. the NIBN, the Faculty of Health Sciences, Ben-Gurion University of the Negev and Head, Oncology Division, Soroka Medical Center, Beer Sheva, Israel

For further information, please contact us at: E-mail: nibn@bgu.ac.il , Tel.: +972-8-647-7193