A new study has found the mechanism behind the ability of obesity to promote cancer progression.
Massachusetts General Hospital (MGH) investigators described finding an association between obesity and an overabundance of a factor called PlGF (placental growth factor) and that PlGF’s binding to its receptor VEGFR-1, which is expressed on immune cells within tumors, promotes tumor progression.
Their findings in cellular and animal models, as well as in patient tumor samples, indicate that targeting the PlGF/ VEGFR-1 pathway may be particularly effective in obese patients.
Co-senior author Dai Fukumura said that they found that obesity increased infiltration of tumor-promoting immune cells and the growth and metastasis of pancreatic cancers.
Fukumura noted that blocking VEGFR-1 signaling shifted the immune environment towards prevention of tumor progression in obese but not in lean mice in both pancreatic and breast cancer models. They also found that PlGF was present in excess in obesity and that reduction of PlGF produced similar results to VEGFR-1 inhibition in the tumors of obese mice.
Lead author Joao Incio said that understanding the way that obesity affects pancreatic and other cancers may help us identify biomarkers, such as body weight and increased levels of PlGF, which could identify patients for whom anti-VEGFR-1 treatment would be most beneficial.
Incio added that people should incorporate body weight into the design of pre-clinical studies in order to better reflect the lack of response to novel targeted therapies such as anti-VEGF. Targeting inflammation holds the promise to improve the clinical outcome of a major subset of cancer patients.
The study is published online in the journal Clinical Cancer Research.