A new drug delivery system using nanoparticles has shown promise in overcoming drug resistance in non-small cell lung cancer (NSCLC). Researchers at the National University of Singapore (NUS), in collaboration with the Cancer Science Institute of Singapore (CSI Singapore) and other institutions, have developed a method to deliver antisense oligonucleotide (ASO) molecules directly to lung cancer cells using extracellular vesicles (EVs) derived from red blood cells.
Targeting Mutant EGFR with Precision
The team focused on mutant Epidermal Growth Factor Receptors (EGFRs), a major driver of lung cancer, particularly in Asian populations. According to Assistant Professor Minh Le, "Mutant Epidermal Growth Factor Receptors (EGFRs) are a major driver of lung cancer in the Asian population. Our focus was on targeting these EGFR mutations, which contribute to cancer's resistance to standard drugs known as tyrosine kinase inhibitors (TKIs)." The ASOs work by adhering to specific sections of ribonucleic acid (RNA) to inhibit irregular activity, which can be easily adapted to target unique genetic mutations within cancer cells.
Overcoming Delivery Challenges
ASOs degrade quickly in the bloodstream, leading to diluted effects at tumor sites. To overcome this, the team devised a novel method of direct delivery using extracellular vesicles (EVs) derived from human red blood cells. These EVs, primed with EGFR-targeting molecules, act as guided carriers, delivering ASOs specifically to the tumor site.
Promising Results in Lung Cancer Models
The ASO-loaded EVs showed significant anti-cancer activity in various lung cancer models, including patient-derived cells, by targeting and inhibiting mutant EGFR while sparing normal cells. This innovative design also demonstrated efficacy against TKI-resistant cancer cells, an advance that holds promise for patients with limited treatment options. Associate Professor Tam Wai Leong stated, "The use of extracellular vesicles as delivery vehicles for nucleic acid therapeutics introduces a powerful new modality in cancer treatment. This precise targeting of mutant EGFR cells, while leaving healthy tissue intact, represents a step forward in tackling cancer drug resistance and advancing personalized medicine."
Implications for Personalized Cancer Treatment
This research is a proof of concept for targeting the vulnerabilities of tumor cells with therapeutic RNA, opening new doors for precision cancer treatments. Professor Goh Boon Cher emphasized, "This research is a proof of concept for targeting the vulnerabilities of tumor cells with therapeutic RNA, opening new doors for precision cancer treatments."
