Researchers report that tumors can become resistant to drugs over time by learning to steal normal blood vessels from surrounding tissue in a process called vessel co-option. The process of new blood vessel growth, angiogenesis, is important for cancers to grow, and several antiangiogenic drugs have been developed to combat it. However, cancers often become resistant to these drugs through mechanisms that until now were poorly understood.
The study, published in the Journal of the National Cancer Institute by scientists from The Institute of Cancer Research, London, and Sunnybrook Research Institute, University of Toronto, shows it could be possible to treat cancers by designing new therapies that block both vessel co-option and angiogenesis. These may be more effective than existing treatments, which only block angiogenesis, according to the investigators, who used mice to examine how hepatocellular carcinoma can become resistant to an antiangiogenic drug called sorafenib.
The team discovered that tumors that responded to treatment initially relied mainly on growing their own blood vessels, but developed resistance to treatment by actively stealing the normal pre-existing blood vessels of the liver instead. The researchers believe their study may have implications not only for the treatment of liver cancer, but also for other cancer types, including metastatic breast cancer and metastatic bowel cancer.
The scientists also found that the switch to vessel co-option was reversible. On stopping treatment, the tumors switched back to using angiogenesis, providing a potential explanation as to why some patients can respond again to the same antiangiogenic drug after they have been off treatment for some time.
Because there are no existing drugs that target vessel co-option, the researchers also carried out experiments to identify how vessel co-option works. They discovered that the cancer cells increase their ability to move when they co-opt vessels, suggesting that targeting cancer cell movement might be used to block vessel co-option.
“Our study is the first to show that cancers can adapt to treatment by actively co-opting blood vessels from nearby tissues as a mechanism of drug resistance,” said Andrew Reynolds, Ph.D., leader of the Tumor Biology team at The Institute of Cancer Research. “In the future, we hope our results will lead to the development of new drug types that target vessel co-option. We believe that drugs which are designed to target vessel co-option could be particularly effective when used alongside existing therapies that block new blood vessel growth.
“Although the current study was focused on liver cancer in mice, we are also currently investigating whether our results are relevant for patients affected by breast and bowel cancer. Our research also emphasizes the importance of further studies to better understand the process of vessel co-option, which seems to play an important role in tumor growth but has been relatively under-studied.”