Innovative Approach in Singapore: Using Exosomes to Combat TKI-Resistant Cancer
In a groundbreaking development, researchers from the National Cancer Centre Singapore (NCCS) have successfully utilized exosomes to target resistant squamous cell cancer tumors. This pioneering study marks the first instance in Singapore where exosomes have been employed to combat TKI-resistant cancers, offering a beacon of hope for patients who previously had limited treatment options. The findings of this study were recently published in the prestigious journal Developmental Cell, signaling a significant milestone in cancer research.
At the heart of this research is the epidermal growth factor receptor (EGFR), a biomarker frequently implicated in various forms of cancer. EGFR-tyrosine kinase inhibitors (TKIs) are a class of drugs commonly used to target and treat cancers associated with EGFR. However, the effectiveness of EGFR-TKI treatments has been inconsistent, particularly in squamous cell cancers, which are known to be among the deadliest types of cancer worldwide. Despite the high prevalence of EGFR overexpression in these cancers, many patients do not respond to EGFR-targeting drugs, presenting a significant challenge for oncologists.
Professor Gopal Iyer, head of the Department of Head and Neck Surgery at NCCS, has been at the forefront of this research. His team primarily focuses on head and neck squamous cell cancers (HNSCC), where over 80-90% of tumors exhibit EGFR overexpression. Despite the widespread presence of this biomarker, Professor Iyer observed that a majority of patients did not respond to EGFR-targeting treatments. This observation prompted further investigation into the underlying mechanisms of resistance, leading to a pivotal discovery in 2017.
In 2017, Professor Iyer and his team identified a genetic mutation in a subset of HNSCC patients that rendered them sensitive to EGFR-TKIs. This mutation resulted in low levels of EGFR antisense RNA 1 (EGFR-AS1) and high levels of a specific isoform of EGFR known as isoform D. However, this mutation was found in only 3-5% of HNSCC patients, leaving the vast majority without an effective treatment option. This discovery set the stage for further research aimed at extending these findings to a broader patient population.
The most recent work by Professor Iyer’s team has revealed that the EGFR isoform D produced by sensitive tumors can be secreted. They demonstrated that this isoform is carried as cargo in exosomes, which are small particles secreted by living cells containing DNA, RNA, lipids, and proteins. These exosomes can influence the function and behavior of other cells they encounter. By producing large volumes of exosomes with high levels of EGFR isoform D, the team was able to transfer sensitivity to EGFR-TKIs to resistant cancer cells in both laboratory and mouse models.
This innovative approach has shown promising results, significantly increasing the sensitivity of resistant cancer cells to various types of EGFR-TKIs. The ability to transfer drug sensitivity through exosomes represents a novel and potentially transformative strategy in cancer treatment. The implications of this research are far-reaching, offering a new treatment avenue for a large group of cancer patients who previously had limited options. The team’s findings underscore the potential of exosomes as a therapeutic tool in overcoming drug resistance in cancer.
To bring this promising therapy closer to clinical application, the team plans to scale up exosome production for early-stage clinical trials. They are currently in discussions with industry and academic partners to facilitate this transition. The research has garnered support from the Singapore Ministry of Health through the National Medical Research Council, highlighting the importance and potential impact of this work. The National Cancer Centre Singapore continues to offer world-class care and conduct cutting-edge research in collaboration with both local and international partners.
The journey to this groundbreaking discovery began with the identification of a genetic mutation in 2015 that made some squamous cell carcinomas curable with a lung cancer drug. Building on this initial finding, the team developed a method to improve treatment effectiveness for tumors in the nose and larynx area. This method involves introducing a protein into the bloodstream of patients, which has shown promising results in laboratory animals and is set to undergo clinical trials soon. The experimental therapy targets squamous cell carcinomas in the nose and larynx area, leveraging the protein isoform D carried by exosomes.
The significance of exosomes in this context cannot be overstated. These small particles play a crucial role in cell-to-cell communication and have been implicated in the development and progression of various diseases, including cancer. By harnessing the natural properties of exosomes, researchers can potentially manipulate the cellular environment to favor therapeutic outcomes. The ability to deliver specific proteins, such as EGFR isoform D, directly to resistant cancer cells opens up new avenues for targeted therapy, reducing the likelihood of adverse side effects associated with conventional treatments.
The potential of this research extends beyond just head and neck cancers. The principles underlying the use of exosomes to transfer drug sensitivity could be applied to other types of cancer as well. The versatility of exosomes as delivery vehicles makes them an attractive option for various therapeutic applications. Future research will likely explore the broader applicability of this approach, potentially revolutionizing the way we treat resistant cancers across different cancer types.
As the team moves forward with clinical trials, the collaboration with industry partners will be crucial in scaling up production and ensuring the feasibility of this therapy in a clinical setting. The transition from laboratory research to clinical application is a complex process that requires meticulous planning and coordination. However, the potential benefits for patients make this endeavor worthwhile. If successful, this therapy could significantly improve the prognosis for patients with TKI-resistant cancers, offering new hope where there was little before.
In conclusion, the innovative use of exosomes to combat TKI-resistant cancer represents a significant advancement in cancer research. The work of Professor Gopal Iyer and his team at the National Cancer Centre Singapore has opened up new possibilities for treating resistant cancers, particularly head and neck squamous cell carcinomas. By leveraging the natural properties of exosomes, the team has developed a novel approach that could potentially transform cancer treatment. As this research progresses towards clinical trials, it holds the promise of offering new hope to a larger population of cancer patients, ultimately improving outcomes and quality of life.
The continued support from the Singapore Ministry of Health and collaborations with industry and academic partners will be instrumental in bringing this promising therapy to fruition. The National Cancer Centre Singapore remains at the forefront of cancer research, dedicated to advancing our understanding of cancer and developing innovative treatments. The use of exosomes to overcome drug resistance is a testament to the power of scientific innovation and collaboration in the fight against cancer.