Selective Targeting of the L858R Mutation (EGFR) in Non-Small Cell Lung Cancer : A Mechanism for Advancing Targeted Chemotherapy and Minimizing Drug Resistance

I've been working on a small molecule based targed cancer therapy project for the past few months. The abstract is below.

Lung cancer remains one of today's most deadly and intractable cancers. Non- Small Cell Lung Cancer (NSCLC) accounts for roughly 85% of lung cancers, with an extremely poor survival rate. Past Findings implicate the EGF/EGFR signaling pathway in NSCLC, specifically L858R mutation occurrence in EGFR, suggesting that a targeted therapy through L858R-mutated EGFR may provide a promising approach to treatment. Therefore, this study attempts to identify a small molecule that would bind to L858R-mutated EGFR to potentially carry cytotoxic compounds into malignant cells. Using AutoDock Vina, 38000 small molecules were screened for ability to bind to non-functional sites on L858R-mutated EGFR (non-functional sites were used to reduce probability of acquired mutational resistance) but not wildtype EGFR, and a top candidate (ZINC000004070447) was identified. This candidate was then conjugated with Bovine Serum Albumin to simulate the molecules linkage with chemotherapy drugs, and the complexs efectiveness was tested through an ELISA. The results indicate that the identified molecule does not interfere with EGF/EGFR interactions and efectively targets only L858R-mutated EGFR. If proven to work in clinical trials, this research can provide a breakthrough in targeted cancer therapy and prevent acquired resistance to drugs

If you are intersted and would like to read more, the full research paper can be found here. If you would like to learn more about the project, feel free to email me!