A team led by Ludwig Harvard’s Rakesh Jain developed a new method of microscopy to image oxygen levels within cells and tissues in relation to blood vessels and applied it to observe the heterogeneity of oxygenation within tumors. The blood vessels that feed tumors tend to be very leaky, resulting in poor perfusion and oxygenation that contributes to resistance to both chemo and immunotherapies. Rakesh has proposed and extensively vetted the hypothesis that normalizing tumor blood vessels could help overcome the drug resistance of many solid tumors. He and his colleagues have shown that the blood supply to tumors is compromised by their leakiness and by compressive forces associated with the tumor mass. The former, they’ve shown, can be reversed with drugs that inhibit signaling through the vascular endothelial growth factor receptor (VEGFR)—which promotes angiogenesis—while the latter can be overcome with angiotensin system inhibitors. Both approaches have been or are currently being evaluated in clinical trials. In a May paper in Clinical Cancer Research, Rakesh and his colleagues reported that both the antiangiogenic blockade of VEGFR2 (using antibody DC101) and an angiotensin-receptor blocker (losartan) improve oxygenation in mouse tumor models, but to varying degrees depending on tumor type and dosage. Their findings also suggest that combining the two therapies is likely to achieve the best results.
Read the study: Multiphoton Phosphorescence Quenching Microscopy Reveals Kinetics of Tumor Oxygenation during Antiangiogenesis and Angiotensin Signaling Inhibition, Clinical Cancer Research, 2022 May 18 Epub
This article appeared in the September 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).