FM Pekris, JW Baish , T. Stylianopoulos T, and RK Jain from the Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia , Cyprus, the Department of Biomedical Engineering, Bucknell University, Lewisburg, the Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia 1678, Cyprus and the Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, USA have just pubiseehd in the Proc Natl Acad Sci U S A. a article entitled : Role of vascular normalization in benefit from metronomic chemotherapy.
In this work, the authors integrate in a mathematical model the multiple mechanisms of metronomic chemotherapy , how these mechanisms are related to one another. They report that MC leads to an improved function of tumor vessels which turns out to be a key determinant of benefit from MC. Using multiple dosage schedules and incorporation interactions among cancer cells, stem-like cancer cells, immune cells, and the tumor vasculature, the authors have found that MC induces functional normalization of tumor blood vessels. This normalization results in turn in improved tumor perfusion and cascade decreased hypoxia, reprogramming of the immunosuppressive tumor microenvironment toward immunostimulation and also improved drug delivery and ultimately therapeutic outcomes. This mathematical model has valuable biological translation and enables evaluation of the relative importance of these mechanisms, and suggests guidelines for the optimal use of MC.