2021 Re-Engineering The Tumor Microenvironment Using Mechano-Therapeutics To Improve Cancer Therapy
Tumor growth at the expense of the host tissue is associated with the development and accumulation of mechanical forces within structural components of the tumor. These forces, known as solid stress, when directly applied to cancer and stromal (non-cancerous) cells can increase their metastatic potential, while when applied to tumor blood vessels, cause vessel compression and eventually collapse. Vessel compression/collapse in turn results in hypo-perfusion and thus, hypoxia and compromised intratumoral delivery of drugs. Hypoxia can also induce immuno-suppression, reducing the anti-tumor activity of immune cells, and drive metastasis to more oxygenated regions. Given the important role of mechanics in tumor progression and therapy, my research team has investigated the causes, consequences and remedies of solid stress, analysing the Mechanopathology of solid tumors. We found that solid stress is elevated in both murine and human tumors, and identified tumor extracellular matrix and cancer-associated fibroblasts as the main contributors to solid stress elevation and vessel compression. We further showed that re-purposing approved drugs, such as common anti-hypertensives, antihistamines, corticosteroids and anti-fibrotic drugs, can act as Mechanotherapeutics, alleviating solid and fluid stresses in tumors, decompressing tumor vessels and thus, improving significantly perfusion and the efficacy of chemotherapy, nanomedicine and immunotherapy in preclinical tumor models. There is now an urgent need to develop clinically applied Mechanical Biomarkers to characterize the mechanical and perfused state of a tumor prior treatment for prediction of cancer therapy as well as monitor changes in the tumor mechanical properties for optimal, patient-specific use of Mechanotherapeutics in humans. In my talk, I will summarize the work of my Cancer Biophysics Laboratory in this exciting and rapidly evolving field of the application of physical sciences and engineering in oncology
Triantafyllos Stylianopoulos is an Associate Professor of Mechanical Engineering and the Head of the Cancer Biophysics Laboratory at the University of Cyprus. He received a Diploma in Chemical Engineering from NTUA, Greece (2003) and a PhD also in Chemical Engineering with a focus on Multiscale Computational Biomechanics from the University of Minnesota (2008). During his postdoctoral training at the Massachusetts General Hospital and Harvard Medical School, he was specialized in experimental Cancer Research for the enhancement of drug delivery to solid tumors (2008-2010). Triantafyllos has published more than 110 articles in peer reviewed journals in the fields of tumor microenvironment, drug delivery and biomechanics. He has secured > €6.0M in research funding as a Principal Investigator, including two frontier grants by the European Research Council (ERC) that supports academic excellence in Europe: an ERC Starting Grant (ReEngineeringCancer, 2014-2018) and an ERC Consolidator Grant (Immuno-Predictor, 2020-2025). In 2016, he was awarded the Y.C. Fung Early Career Award by the Bioengineering Division of the American Society of Mechanical Engineers. He was also the recipient of the Most Cited article award (2014) and the Athanasiou ABME student award (2019) by the BioMedical Engineering Society of the USA for articles published in Annals of Biomedical Engineering. Triantafyllos has trained 12 post-doctoral fellows, 8 PhD students and more than 45 Master and undergraduate students.
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