The spread of cancer cells leads to what is called "solid stress," a phenomenon that can hinder the effectiveness of anticancer treatments. Now a team of researchers at Massachusetts General Hospital in Boston has identified factors that contribute to solid stress in tumors an discovered a way to lessen it. The study was published in Proceedings of the National Academy of Sciences.
A release from the hospital quotes lead author Rakesh Jain, PhD as saying, "Traditionally cancer research has focused on cancer cells and, more recently, on the biochemical microenvironment of tumors. Our work shows that the physical or mechanical microenvironment plays an equally important role in tumor progression and treatment resistance."
Jain and his colleagues have been forerunners in research about the impact of elevated fluid pressures that make it harder for drugs to penetrate and permeate tumors. Their earlier work showed that fluid pressures are relieved when "antiangiogenesis" drugs – medications that prevent the growth of new blood vessels -- normalize the abnormal blood vessels typical of solid tumors. The team found that this approach improves the effectiveness of other anticancer therapies but that the technique won't work if vessels have been "squeezed shut by solid stress in surrounding tissues."
That's why their current study involved the development of a strikingly simple way to measure solid stress in tumors as well as to identify factors that contribute to solid stress and to alleviate the pressure. According to the authors, "freshly excised tumors can be cut in a specific way that relaxes growth-induced stresses and causes the tissues to deform in a measurable way. Mathematical models can then calculate the stored stress based on the measured deformation and the tumor’s mechanical properties."
Beyond that, the investigators demonstrated that reducing solid stresses by "therapeutically depleting tumor-associated fibroblasts or extracellular matrix decompresses blood and lymphatic vessels, which increases tumor blood flow." In sum, the findings demonstrate a technique that can potentially serve as a rapid screen for stress-reducing and perfusion-enhancing drugs.
