Lung Cancer Breakthrough: EVs for Precision Drug Delivery

On November 11, 2024, significant advancements in lung cancer treatment were reported by researchers from the NUS Yong Loo Lin School of Medicine. A groundbreaking study demonstrated the efficacy of using microcellular drones, specifically extracellular vesicles (EVs) derived from red blood cells, to deliver customized anti-cancer drugs directly to tumors, marking a promising development in precision medicine tailored for lung cancer patients.

Lung Cancer: An Urgent Medical Challenge

Lung cancer, particularly non-small cell lung cancer (NSCLC)—the predominant type among non-smokers—remains a leading cause of cancer mortality globally. The persistence and rapid emergence of drug resistance due to mutations in cancer cells have posed significant challenges, necessitating the exploration of novel therapeutic approaches.

Innovative Drug Delivery System

Research led by Assistant Professor Minh Le from the Institute for Digital Medicine (WisDM) and the Department of Pharmacology highlights a novel utilization of extracellular vesicles (EVs) as nanocarriers for delivering antisense oligonucleotides (ASOs) targeting mutations related to lung cancer.

What are Extracellular Vesicles?

Extracellular vesicles are nano-sized particles naturally released by cells. In this study, the researchers repurposed EVs derived from red blood cells to function as drug delivery systems:

• These EVs can carry antisense oligonucleotides that specifically inhibit the activity of mutated epidermal growth factor receptors (EGFRs), which are prevalent in NSCLC.
• The design of ASOs allows them to specifically bind and inhibit abnormal RNA activity, a key factor in cancer progression.

Methodology

The study involved several key steps:

1. Characterization of EVs: The researchers assessed the composition and loading efficiency of the RBCEVs and their capability to carry ASOs effectively.
2. Engineering Targeting Moieties: The EVs were modified with specific targeting molecules to enhance their ability to home in on cancer cells.
3. In Vitro Testing: The anti-cancer efficacy of ASO-loaded EVs was tested on various cancer cell models, including patient-derived cells.

Results and Findings

Implications for Precision Medicine

The innovative approach of utilizing EVs for drug delivery represents an important milestone in combating drug resistance encountered in standard cancer treatments.

• The flexibility of ASOs allows for rapid adaptation to target new mutations as they arise, a significant advantage in the evolving landscape of cancer therapy.
• This method could pave the way for individualized treatment strategies that are specifically tailored to the genetic makeup of each patient’s tumor.

“The ability to precisely eliminate mutant EGFR cancer cells while sparing normal tissues will enable customized treatment for individual patients.” – Associate Professor Tam Wai Leong, A*STAR GIS

Future Directions

Looking ahead, this research lays a foundation for further studies aimed at refining the delivery mechanisms and expanding the application of this technology in various cancer therapies. Key areas of focus include:

• Enhancing the stability and half-life of ASOs in circulation.
• Conducting clinical trials to evaluate safety and efficacy in human subjects.
• Exploring the potential of ASO-loaded EVs for targeting other cancer types beyond lung cancer.

Conclusion

The innovative use of extracellular vesicles as a delivery system for nucleic acid therapeutics positions this approach as a promising avenue in the fight against cancer, particularly in addressing the challenges of drug resistance and the implementation of personalized medicine.

Further Reading

More information can be found in the article by Trinh T.T. Tran et al. titled “Customized design of antisense oligonucleotides targeting EGFR driver mutants for personalised treatment of non-small cell lung cancer” published in eBioMedicine (2024).

[1] Lifespan.io