Key Takeaways:
- The critical balance of oxygen in human cells is regulated by an intricate oxygen-sensing process in the body.
- When cancer cells hijack the process, they can fuel their own growth and gain the ability to metastasize and resist chemotherapy and radiation treatment.
- The difference in oxygen levels between cancer cells and normal cells has inspired the development of a new class of medicine for cancer.
Normal human cells need just the right amount of oxygen — not too much and not too little — to survive and stay healthy. This critical balance is regulated by an intricate oxygen-sensing process in the body, the discovery of which earned the 2019 Nobel Prize in Medicine shared by Dana-Farber scientist William G. Kaelin, Jr., MD, and two other researchers. This mechanism enables people to adapt to living at high altitudes and bring more oxygen to cells during exercise — but it can also be hijacked by cancer cells for their own survival.
Cancer cells often are starved of oxygen — a condition called hypoxia. One instance where this might occur is when enlarging tumors outgrow the network of blood vessels that supplies tumor cells with oxygen. A key component of the body’s oxygen-sensing system is a set of molecular hypoxia-inducible factors, or HIFs, which can respond to a need for more oxygen by turning on genes and proteins that recruit new networks of blood vessels.
Cancer cells in a growing tumor can adapt to oxygen deprivation by hijacking these HIFs. The HIFs can initiate the formation of new blood vessels to improve oxygen delivery. In addition, the HIFs change how cancer cells metabolize glucose (sugar) so that it can still be used to make energy even in the absence of oxygen.
Consequently, a first-in-class anticancer drug called belzutifan, discovered based on Dana-Farber science, was developed to thwart tumor growth by directly blocking HIF activity. Belzutifan has been approved by the U.S. Food and Drug Administration for the treatment of Von Hippel-Lindau disease and advanced kidney cancer.
Belzutifan is currently being studied in clinical trials led by Dana-Farber’s Toni K. Choueiri, MD, in combination with other therapies, such as immunotherapy. Choueiri is also exploring the possibility that the drug can be used earlier in kidney cancer treatment or can be effective in staving off relapse. Further, next-generation HIF2a inhibitors are also being studied in early-stage clinical trials to assess their safety and effectiveness.
Does oxygen cause cancers to grow or spread?
The complex relationship between oxygen and cancer has been a subject of ongoing research as well as a source of mistaken ideas. One persistent myth is that surgery, by exposing cancers to oxygen in the ambient air, will accelerate cancer spread and lead to worse outcomes. This belief fosters worry about undergoing cancer surgery.
“Exposure to air will not make tumors grow faster or cause cancer to spread to other parts of the body,” the National Cancer Institute says.
Hyperbaric oxygen therapy for cancer
Another unproven idea about oxygen and cancer is that, since many tumors thrive in oxygen-deprived (hypoxic) conditions, giving cancer cells extra oxygen might shut them down or even kill them. That’s the notion behind hyperbaric oxygen therapy — oxygen administered to a patient in a chamber under high pressure to increase its concentration in the blood, as is sometimes done to improve wound healing.
According to the U.S. Food and Drug Administration, there is no evidence that this treatment is effective in treating cancer and a long list of other conditions for which it has at times been suggested.
Other forms of “oxygen therapy” for cancer that have been tried over many years include giving oxygen-containing substances like ozone or hydrogen peroxide, by injection or orally. The American Cancer Society has said “there is no scientific evidence that hydrogen peroxide is a safe, effective, or useful cancer treatment” and may cause harm.
