Illustration of extracellular vesicles in cancerIntroduction

Extracellular vesicles (EVs) are small membrane-bound particles secreted by cells that play a crucial role in intercellular communication. Their ability to transfer bioactive molecules such as proteins, lipids, and nucleic acids between cells has positioned them as significant players in both physiological and pathological processes, including cancer. Three recently published articles have shown the impact of EVs on cancers, their roles in promoting cancer cell survival, potential as therapeutic agents, and their innovative use in non-invasive cancer detection.

The Dual Role of Extracellular Vesicles in Cancer Progression and Therapy

Survival Mechanisms in Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of malignant B-cells within the blood, bone marrow, lymph nodes, and spleen. These CLL-B-cells are notably resistant to apoptosis and exhibit low proliferation rates. The tumor microenvironment (TME) plays a significant role in this resistance, providing survival signals through interactions with various accessory cells, including mesenchymal stromal cells (MSC), nurse-like cells (NLCs), and T cells.

In a study published in the journal Cancer Gene Therapy, researchers from the University of Limoges demonstrated that EVs derived from nurse-like cells and M2-polarized THP1 macrophages are rapidly internalized by CLL-B-cells, leading to decreased apoptosis and increased proliferation. The transcriptomic analysis revealed upregulation of anti-apoptotic genes such as BCL-2 and APRIL, along with increased expression of proteins involved in apoptosis regulation, including IGFBP-2, CD40, p53, and BCL-2. These findings suggest that EVs from the TME, particularly those from NLCs and M2-THP1 cells, significantly contribute to the survival and proliferation of CLL-B-cells. Targeting EV-mediated communication in the TME could thus be a promising therapeutic strategy for CLL.

Therapeutic Potential in Pancreatic Cancer

In contrast to their role in promoting cancer cell survival in CLL, EVs can also be engineered to enhance cancer therapy. A study published in the journal Signal Transduction and Targeted Therapy, led by researchers from the Second Affiliated Hospital of Nanjing Medical University, China, explored the use of engineered extracellular vesicles for targeted reprogramming of cancer-associated fibroblasts (CAFs) in pancreatic cancer. These fibroblasts play a pivotal role in the desmoplastic reaction, contributing to the dense stromal environment that characterizes pancreatic tumors and impedes therapeutic efficacy.

The study utilized EVs engineered to deliver specific cargo that could reprogram CAFs, transforming them from a tumor-promoting to a tumor-suppressing phenotype. These reprogrammed CAFs exhibited reduced proliferation and increased sensitivity to chemotherapy, highlighting the potential of EVs as a delivery system for therapeutic agents in cancer treatment.

Revolutionizing Liver Cancer Detection: AI-Driven Blood Test

A novel AI-driven blood test developed by Mursla Bio leverages advanced analysis of liver-derived extracellular vesicles (EVs) for non-invasive liver cancer surveillance, marking a significant leap in early detection and monitoring. This innovative approach utilizes the Nano-Extracellular Omics Sensing (NEXOS) platform, which combines electrical and optical detection methods to achieve ultrasensitive and phenotypic characterization of small EV sub-types and their protein epitope counts. By precisely examining rare tissue-specific EVs in the bloodstream, the test detects critical biological materials such as DNA, RNA, proteins, and lipids from the liver. The AI-empowered biomarker discovery platform identifies disease biosignatures, including early indicators of liver cancer, offering enhanced specificity and accuracy over traditional screening techniques like ultrasound. This real-time, non-invasive alternative to tissue biopsies promises to improve early diagnosis and patient outcomes, facilitating personalized treatment strategies and better clinical care.

EVs in the Spotlight: Biomarkers, Drug Delivery, and Personalized Medicine

The multifaceted nature of EVs in cancer paves the way for exciting advancements in cancer diagnosis and treatment. EVs hold promise as biomarkers for cancer detection and monitoring disease progression. Additionally, targeting EVs or their cargo offers a novel therapeutic approach. The ability to engineer EVs for specific functions opens doors to personalized cancer therapies. By tailoring these engineered EVs to target a patient’s unique tumor microenvironment, clinicians can potentially achieve more effective and targeted treatment strategies.

Conclusion

Extracellular vesicles represent a double-edged sword in the realm of cancer biology. Their ability to promote cancer cell survival in hematological malignancies like CLL highlights the need for therapeutic strategies that target EV-mediated communication. On the other hand, their potential as carriers for therapeutic agents in solid tumors such as pancreatic cancer offers a promising avenue for enhancing cancer treatment. Moreover, the development of AI-driven blood tests for non-invasive liver cancer detection showcases the innovative applications of EVs in oncology. As our understanding of EVs continues to grow, so too will their potential to transform cancer therapy, offering hope for more effective and targeted treatments in the future.

References

  1. Ikhlef L, Ratti N, Durand S, et al. Extracellular vesicles from type-2 macrophages increase the survival of chronic lymphocytic leukemia cells ex vivo. Cancer Gene Ther (2024). https://doi.org/10.1038/s41417-024-00802-7
  2. Zhou P, Du X, Jia W, et al. Engineered extracellular vesicles for targeted reprogramming of cancer-associated fibroblasts to potentiate therapy of pancreatic cancer. Sig Transduct Target Ther 9, 151 (2024). https://doi.org/10.1038/s41392-024-01872-7
  3. Dias T, Figueiras R, Vagueiro S, et al. An electro-optical platform for the ultrasensitive detection of small extracellular vesicle sub-types and their protein epitope counts. iScience 27, 109866 (2024). https://doi.org/10.1016/j.isci.2024.109866

Need Help or Have Questions on Assays for EVs

How Can We Help You with Your Projects?

Contact us to discuss the specifics of your project. Our team of experienced scientists is ready to assist you with tailored solutions to meet your unique needs. Whether you need help with assay development, FDA IND stability study, lot release approval, or other scientific endeavors, we are here to support you.

How Long Does It Take to Get Started?

We will initiate your project as soon as the proposal is approved and signed by you. Our streamlined process ensures a quick start, minimizing delays and maximizing efficiency.

Can You Help with Assay Development and Validation for FDA IND Lot Release and Stability Study Approval?

Yes, we have over 30 years of expertise in developing and validating cell-based assays for FDA IND lot release or stability study approval. Our team can also liaise directly with the FDA on your behalf, ensuring a smooth and compliant process. Please contact us to learn more about how we can assist you with your assay development and FDA approval needs.

Do You Need a Custom or Tailored Assay?

MarinBio scientists are experienced and creative in designing, developing, and validating assays. Some of the assays we perform are listed below, but there are many more that we have created, developed, and validated. Give us a call so that we may help you.

ADD THE CONTACT US FORM HERE