Antiangiogenic drugs are effective in some cancers, where they help to reverse the tumour hypoxia (oxygen deficiency) that encourages tumour growth. However, treatment resistance is a serious problem.
As reported in Cell Reports (online, 9 June 2016)
, a team of researchers explored the mechanisms of resistance to antiangiogenic multi-tyrosine kinase inhibitors (TKIs) in mouse models of lung and breast cancer.
They showed that when TKIs correct hypoxia, tumour cells downregulate glycolysis and become reliant on mitochondrial metabolism for energy and continued growth. Adding the antidiabetic drug phenformin, which is a mitochondrial blocker, to treatment resulted in a reduction in tumour growth.
The team, from the Spanish National Cancer Research Centre, is now designing a phase I trial to explore the safety and efficacy of combined TKI and phenformin treatment.