RESEARCHERS have developed a promising new treatment strategy for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, addressing a major challenge in cancer therapy: drug resistance. Tyrosine kinase inhibitors (TKIs) have long been the standard treatment for EGFR-mutant NSCLC, but the emergence of drug-resistant mutations, such as T790M, often leads to treatment failure. Additionally, TKIs can cause severe side effects due to their non-specific inhibition of wild-type (WT) EGFR.
In a breakthrough study, scientists have designed customised antisense oligonucleotides (ASOs) that selectively target and inhibit specific EGFR mutations, including the common L858R and T790M mutations, without affecting WT EGFR. By using extracellular vesicles (EVs) as a delivery method, the researchers were able to effectively transport the ASOs directly to cancer cells, avoiding the toxicities associated with traditional treatments.
In preclinical models, the EGFR-targeting ASOs led to a substantial reduction in tumour growth in EGFR-mutant NSCLC, even in cases resistant to TKIs. These results suggest that ASOs could offer a more targeted and potent treatment option, providing a viable alternative for patients who have developed resistance to standard therapies. The research represents a promising step toward more effective and adaptable therapies for NSCLC.
Reference
Tran T et al. Customised design of antisense oligonucleotides targeting EGFR driver mutants for personalised treatment of non-small cell lung cancer. eBioMedicine. 2024;108:105356.
