Scientists are developing and monitoring two approaches to correcting blood vessel abnormalities that complicate tumor treatment

Tumors send signals that disrupt normal blood flow, making them difficult to treat with any type of cancer treatment, including radiation and chemotherapy, targeted and immunotherapy. Impaired blood supply creates an environment with low oxygen content – hypoxia – which causes tumors to acquire aggressive characteristics and suppress immunity. To address this problem, a team led by researchers from the Massachusetts General Hospital (MGH) developed two approaches to repairing blood vessel tumors and improving their function. In addition, by developing a method for evaluating the effects of these approaches and testing it in a study published in Clinical studies of cancerJournal of the American Association for Cancer Research, the researchers found that each approach could help restore blood flow to improve chemotherapy access to cancer cells and alleviate hypoxia, and their combination may be particularly effective.

The method of evaluating scientists involves measurement oxygen level as an indicator of the degree of hypoxia and abnormal bleeding in tumors. “This study reports the development and application of a new microscopy system with unique characteristics,” says senior author Rakesh K. Jain, Ph.D., director of EL Steele’s Laboratory of Tumor Biology at MGH and radiation professor Andrew Werk Cook. Oncology at Harvard Medical School.

“First, this system is capable of creating images oxygen concentration both inside cells and in large volumes tumor fabrics in relation to blood vesselthat carry oxygen. Second, this system can detect oxygen concentrations in tumor tissues over time so that changes in oxygenation can be observed during therapy. ”

Jain and his colleagues used their microscopy system to study the effects of two approaches to repairing blood vessel abnormalities that reduce blood flow: one using antiangiogenic therapy aimed at blood vessel formation, and the other involving so-called angiotensino. inhibitors that can alleviate the compressive forces that occur in growing tumors that break down blood vessels of the tumor. An example of an angiotensin inhibitor is the drug losartan, approved for the treatment of high blood pressure.

“Our microscopy analyzes have shown that, although each approach alleviates hypoxia in tumors, the effects have been mixed – for example, giving different results depending on tumor type and dose,” says co-author John D. Martin, Ph.D. was a PhD student in Steele Laboratories during this study and is now a Research Fellow at Nanocarrier Co., Ltd. in Tokyo. Additional changes in blood vessels in response to these two approaches suggest the possibility of combining them to create a stronger effect.

“Understanding hypoxia in tumors – and how antiangiogenic therapy and losartan affect hypoxia – is important for disease progression and resistance to treatment,” says co-lead author Ryan Lanning, MD, PhD. during this study he was a student of Steele’s lab and is now an associate professor at the University of Colorado School of Medicine.

“Antiangiogenic therapy is used as the standard of care in some cases of lung, kidney, liver and endometrial cancer in combination with chemotherapy and immunotherapy. Similarly, losartan is in a clinical trial with chemotherapy and immunotherapy for pancreatic cancer the leadership of our MGH staff ”.