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. As of today there are no approved treatment for this latter group of patients, representing a very strong unmet need. Our goal is to develop a treatment to patients carrying EGFR TKI-insensitive mutations.
The structure of EGFR has been previously published, with over 100 available structures. 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 TK domain of insensitive mutated EGFR. Additionally, will be tested alternative technologies for inhibiting specific EGFR mutated protein such as antisense which directly targeted the mutations.
- There is currently no approved medication for this population.
- Prof. Peled is key 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.
Prof. Nir Peled, MD, PhD, NIBN, the Faculty of Health Sciences, Ben-Gurion University of the Negev and Head, Oncology Division, Soroka Medical Center, Beer Sheva, Israel