Exosomes, which are excreted by all live cells, contain cell components such as DNA, RNA, lipids, and proteins. When they are released into the bloodstream, they can influence the function and behavior of other cells they encounter.
Exosome therapy is an exciting and innovative area of medical research, as it has been shown that this communication plays a role in the development of various diseases, including cancer, neurological diseases, and inflammatory diseases.
In a recent study, clinician-scientists and researchers at the National Carcinoma Centre Singapore (NCCS) demonstrated the use of exosomes to effectively target squamous cell carcinoma tumors that are typically resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).
This study is the first to use exosomes to target TKI-resistant tumors in Singapore. The researchers published the results in the journal Developmental Cell (1✔ ✔Trusted Source
Therapeutic application of extracellular vesicular EGFR isoform d as a co-drug to target squamous cell cancers with tyrosine kinase inhibitors.
EGFR, or epidermal growth factor receptor, is a biomarker commonly associated with cancer. EGFR-TKIs are a class of medications frequently used to target EGFR for cancer treatment. However, TKIs do not work on many tumors with high EGFR levels, and their effectiveness has been inconsistent.
One of the biggest groups of EGFR-implicated cancers is squamous cell cancer, one of the deadliest cancers worldwide. Professor Gopal Iyer, Head of the Department of Head and Neck Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and NCCS, treats head and neck squamous cell cancers (HNSCC) in which over 80-90% of tumours have overexpressed EGFR. While treating patients in the clinic at NCCS, he observed that the majority do not respond to drugs targeting EGFR. In 2017, Prof Iyer and his research team identified mutations in a rare subset of HNSCC patients that conferred sensitivity to EGFR-TKIs.
The mutation resulted in several changes:
- Low expression of EGFR-AS1
- High expression of EGFR isoform D
Only 3 to 5% of HNSCC harbor these mutations leaving the rest of the patient group without an effective treatment.
Exosomes in Cancer Treatment
Since the initial discovery in 2017, Prof Iyer and the team have worked on extending their initial findings for application to a larger group of patients. In their most recent work, they found that the EGFR isoform D produced by sensitive tumours had certain characteristics that allowed it to be secreted.
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Using patient-derived HSNCC cell lines in the lab, they were able to show that EGFR isoform is carried as cargo in exosomes, and these were taken up by adjacent cancer cells and made sensitive to TKIs.
The team then tested whether this characteristic of sensitivity conferred by high levels of the EGFR isoform D was transferrable from a sensitive cancer to a resistant cancer. They produced large volumes of exosomes producing EGFR isoform D in the lab and treated many cell lines that were resistant to TKIs.
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The exosomal treatment was able to increase the sensitivity of the resistant cell lines to many different types of TKIs. Remarkably, they were able to achieve the same result in vivo using a mouse model, confirming that it is possible to target EGFR TKI-resistant tumours with this strategy.
Opening Exosomes Treasure Chest
On what this means for patients, Professor Iyer, who is also Head of the translational research Division of Medical Sciences at NCCS commented, “Our findings provide new hope for patients as we can potentially target a large population who previously had a poor prognosis for their cancer. We’re excited to partner with industry to move this research to the next phase so that we can start offering therapeutic solutions to our patients in the clinic.”
He also shared what the findings meant for the field of cancer research, “We have opened a treasure chest of how exosomes can potentially be applied to transfer treatment-sensitivity for other cancers. The possibilities are endless for the future of exosomes as yet another weapon in the fight against cancer!”
The research team plans to scale up exosome production so that the findings can be taken into early-stage clinical trials. They are currently in discussions with various industry and academic partners to achieve this goal.
Reference:
- Therapeutic application of extracellular vesicular EGFR isoform d as a co-drug to target squamous cell cancers with tyrosine kinase inhibitors.- (https:www.cell.com/developmental-cell/abstract/S1534-5807(24)00442-8 )
Source-Eurekalert
