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Autotaxin production may shield cancer cells from radiation therapy.
A natural healing mechanism of the body could be dampening the effects of radiation therapy on breast cancer, according to findings from a new study published by The FASEB Journal.
The authors found that irradiation of adipose breast tissue results in an inflammatory response that promotes healing in normal tissue; however, the response allows cancerous cells to survive.
The investigators seek to develop a way to inhibit this natural process.
"Patients often undergo 25 daily doses of radiotherapy to the whole breast after surgical removal of the tumor to ensure that any remaining breast cancer cells are destroyed," said researcher David Brindley, PhD, DSc. "During this treatment, the adipose tissue releases autotaxin, an enzyme that initiates a wound-healing response. This response ends up protecting the remaining cancer cells, allowing them to survive and avoid destruction."
In the study, the authors exposed human and rat adipose tissue to radiation at levels similar to what patients would experience during treatment. They discovered that exposure to radiation increased autotaxin production and the inflammatory wound healing response, according to the study.
“Cancer cells adopt a variety of strategies for avoiding the immune response in the body,” Dr Brindley said. “If we can block the autotaxin response, we think the body would then be more able to use its own immune system to attack residual cancer cells and to eliminate them, particularly when they are already damaged.”
The authors are currently testing an investigational autotaxin inhibitor to determine if the therapy would inhibit the wound healing response. They hypothesize that it would improve the efficacy of radiotherapy.
The experimental drug is also being tested in clinical trials for an inflammatory condition.
“The advantage of attacking the autotaxin as a target is that it is independent of the characteristic and mutations in the tumour [sic],” Dr Brinley said. “We are not targeting the cancer cell itself, but its environment, which should be similar in different tumours [sic]. We’re hopeful that our treatment will be applicable to all kinds of breast cancer and not just a particular subtype.”
The authors believe that an autotaxin inhibitor could be used to treat other types of cancer, such as thyroid cancer and glioblastoma. Additionally, they suggest that same strategy can be used to improve the efficacy of chemotherapy.
The authors said they next hope to move their studies into rodent animal models to determine if the approach works in vivo.
“This is not pie-in-the-sky thinking,” Dr Brindley concluded. “It has great promise.”