Research from OICR Investigator Dr. Anastasia Tikhonova shines a light on the biology behind bone and blood health complications that arise after treatment with chemotherapy.
New OICR research has discovered the biological process behind common long-term side effects of chemotherapy and could offer a new strategy to improve quality of life for cancer survivors.
Chemotherapy remains one of the most common treatments for cancer. But while it’s effective at killing cancer cells, it can also harm other tissue in the body and cause potentially life-changing side effects.
A team of researchers led by OICR Investigator Dr. Anastasia Tikhonova and graduate student Ximing Li set out to explain why many cancer patients treated with chemotherapy struggle with bone and blood health complications for months and sometimes years after their treatment ends.
In a study published in leading hematology journal Blood, they found that a common chemotherapy called doxorubicin causes an immune response that leads to chronic inflammation in bone marrow and nearby cells. Healthy bone marrow helps produces most of the body’s blood and bones cells, but chronic inflammation disrupts its ability to produce blood-forming stem cells and support healthy bones. This can leave bones weaker and more susceptible to breaks and injuries.
“Bone marrow is more than a factory for blood cells, it is a complex environment that supports both blood formation and bone health,” says Tikhonova, a Senior Scientist at Princess Margaret Cancer Centre and Assistant Professor of Medical Biophysics at the University of Toronto. “What we found is that chemotherapy can leave this environment in a prolonged inflammatory state. Even after the chemotherapy is gone, the bone marrow may remain damaged and less able to support normal regeneration. Our goal is to find ways to protect that environment so patients can recover better after treatment.”
In the hopes of curbing potential bone and blood vessel damage in cancer patients, Tikhonova and the research team dug deeper into the process behind the damaging inflammation. They found that doxorubicin causes an immune cell called CD8+ T cells to produce increased levels of a protein called interferon-gamma. An inflammatory signalling protein, or cytokine, interferon-gamma normally helps coordinate immune responses to infections and other foreign substances. But when its levels are persistently elevated, it can also alter surrounding tissues.
Then they looked at whether they could stop that process. They blocked interferon-gamma signalling in mouse models and found that several features of the damaged bone marrow and surrounding microenvironment recovered partially. When they combined this approach with a treatment that promotes vascular recovery, it also reduced chemotherapy-associated skeletal damage.
While there isn’t a current clinically approved way to block interferon during chemotherapy in humans, Tikhonova hopes her team’s discovery provides a head start on a new strategy to improve quality of life.
“Chemotherapy still has an important role to play in cancer treatment, but we need to protect patients from the long-term side effects,” Tikhonova says. “Our study shows you can take a scientific approach to helping people stay healthy and enjoy life after their cancer treatment is over.”
