Leukemic cells can feed themselves through increased secretion of hepatocyte growth factor (HGF), which then activates its receptor, MET, to promote growth. This autocrine loop allows the leukemic cells to sidestep therapeutic inhibition of MET, shows a report published online in this week’s Nature Medicine.
Thomas Look and colleagues use a type of genomic screen and identify abnormal HGF expression as a crucial factor for development of a class of acute leukemia in leukemia cell lines and clinical samples. The team show that treatment with MET inhibitors resulted in drug resistance owing to increased HGF expression to compensate for MET blockade.
The findings illustrate the potential relevance of considering adaptive responses by tumor cells when designing targeted therapies for cancer.