Epidermal growth factor receptor (EGFR) is an essential driver of oncogenic signaling and EGFR inhibitors are some of the earliest examples of successful targeted therapies in multiple types of cancer including lung cancer. Their success as therapeutic targets is overshadowed by the inevitable drug resistance that develops. Overcoming resistance mechanisms requires a deeper understanding of EGFR regulation in cancer cells. Our team has shown that DHHC20 palmitoylates EGFR on the C-terminal domain (CTD) and that expression of a palmitoylation resistant mutant form of EGFR similarly inhibits Kras driven lung adenocarcinoma. Our overarching hypothesis is that palmitoylation rapidly terminates EGFR signaling and that synthetic peptides that mimic the palmitoylated CTD can inhibit EGFR kinase activity through a previously unknown mechanism. We have developed synthetic palmitoylated peptides, capable of inhibiting EGFR kinase activity in vitro and our optimizing them for activity. Notably these peptides are cell permeable and can modulate RTK mediated signaling in cells.

Cell permeable palmitoylated peptides as EGFR Inhibitors

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.