Blocking Ran protein reverses resistance of lung and breast cancers
Researchers at the University of Bradford have discovered a way to prevent chemotherapy resistance in lung cancer by blocking a protein found in cancer cells.
Suppressing this protein, called Ran-GTP, also causes cancer cells already resistant to the first-line chemotherapy treatment, gefitinib, to become re-sensitised to the drug.
The research, led by Professor Mohamed El-Tanani (pictured), at Bradford’s Institute of Cancer Therapeutics in collaboration with Queen’s University Belfast, also found that Ran-GTP could be used to predict prognosis in breast cancer patients.
Key to the findings – published today (04 October) in Oncotarget – is the relationship between Ran-GTP and another protein called c-Met, which has previously been linked to several cancers. Overexpression of c-Met is known to cause chemotherapy resistance in breast and lung cancer and drugs which inhibit its activity are currently undergoing clinical trials for treatment of lung cancer. Professor El-Tanani believes the new research shows that targeting Ran-GTP could be a more effective approach.
“Much is known about the activity of c-Met and its impact on cancer, but our research is looking at things a step earlier, by focusing on the protein that regulates c-Met – Ran-GTP,” he says. “c-Met needs Ran-GTP to function, and in particular needs very high levels when it becomes over-expressed or mutates – as is the case in cancers. By blocking Ran-GTP, we were able to both undo the resistance caused by c-Met and prevent that resistance occurring. This shows that Ran-GTP could be a good therapeutic target for cancer treatment, particularly in lung and breast cancer.”