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Exploiting Exosomal miRNA Signatures for Real-Time Monitoring of Tumor Microenvironment Dynamics and Therapy Adjustment

Jeya Chelliah B.Vsc Ph.D.

Exosomes, the nanoscale extracellular vesicles derived from the endosomal compartment of most eukaryotic cells, have emerged as significant players in intercellular communication. Through their cargo, which includes proteins, lipids, and various forms of RNA, exosomes influence numerous physiological and pathological processes. In the context of cancer, they have been shown to contribute to tumor progression, metastasis, and the sculpting of the tumor microenvironment (TME). This proposal aims to explore a novel research avenue in the utilization of exosomal miRNA signatures as dynamic biomarkers for real-time monitoring of the TME, enabling timely adjustments in cancer therapy.

Background:

Exosomes originate from the inward budding of endosomal membranes, leading to the formation of multivesicular bodies (MVBs). Upon fusion with the plasma membrane, these MVBs release exosomes into the extracellular space, where they can travel to distant sites. The fate of exosomes and their integration into recipient cells facilitate a range of functions, from modulating target cell behavior to transferring oncogenic factors. Their role in cancer has been extensively documented, yet the potential for using exosomal miRNA profiles as a real-time indicator of TME dynamics remains largely untapped.

Novel Research Idea:

Our research proposes a groundbreaking approach to cancer diagnosis, treatment, and monitoring by focusing on the temporal and spatial dynamics of exosomal miRNA signatures within the TME. We hypothesize that these signatures reflect the evolving landscape of the tumor and its microenvironment, providing insights into tumor progression, metastasis potential, and response to therapy. The objectives of this research are:

  1. Characterization of Exosomal miRNA Signatures: To identify and catalog miRNA signatures from exosomes isolated from various cancer types, at different stages, and under various treatment conditions.
  2. Correlation with TME Dynamics: To correlate specific exosomal miRNA patterns with changes in the TME, including angiogenesis, immune cell infiltration, and extracellular matrix remodeling.
  3. Real-Time Monitoring and Predictive Modeling: To develop a non-invasive, real-time monitoring system using liquid biopsies to assess the dynamic changes in exosomal miRNA signatures. This system will be integrated with predictive modeling to forecast tumor behavior and treatment outcomes.
  4. Therapeutic Adjustment Strategy Development: Based on the predictive models, we aim to design a decision-support system for clinicians to adjust therapeutic strategies dynamically in response to changes in the TME, as indicated by exosomal miRNA signatures.

Methodology:

This research will employ a multi-disciplinary approach, incorporating next-generation sequencing (NGS) for miRNA profiling, bioinformatics for data analysis and predictive modeling, and clinical trials to validate our findings. We will collaborate with oncologists to collect longitudinal samples from cancer patients undergoing treatment, allowing us to monitor the evolution of exosomal miRNA signatures in response to therapy.

Impact and Significance:

This novel research idea stands to revolutionize the field of oncology by providing a mechanism for the real-time assessment of the TME and enabling personalized, dynamic adjustments to cancer therapy. By understanding the intricate relationship between exosomal miRNA signatures and the TME, we can enhance the precision of cancer treatment, improve patient outcomes, and reduce the incidence of treatment resistance.

The exploration of exosomal miRNA signatures as a tool for the real-time monitoring of the TME represents an innovative and promising frontier in cancer research. This proposal outlines a comprehensive approach to harnessing the potential of exosomes in cancer diagnosis, treatment, and monitoring, paving the way for a new era of personalized oncology.

This research proposal aims to bridge the gap between our understanding of exosomal biology and the practical application of this knowledge in clinical oncology, offering a novel pathway to the dynamic management of cancer therapy.

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