T-cell acute lymphoblastic leukemia (T-ALL) is a rare form of leukemia, accounting for about 15% of all cases of ALL. In one in five children, the disease comes back after treatment. Often in these children, the current standard treatment of intensive chemotherapy no longer works. New ways to treat the disease are therefore urgently needed.
More complete picture
To find new starting points for targeted therapy for children with recurrent T-ALL, Cordo’ investigated a new angle. She did this together with researchers from the Prinses Máxima Center and Amsterdam UMC. Cordo’ explains: ‘Previously, researchers often only looked at the genetic aspects related to T-ALL. However, an abnormality in the DNA is not the only way of activating the proteins that stimulate tumor cell growth. I investigated a new angle that shows more directly what is happening: kinase activity.'
Kinases activate proteins, they work like ‘switches’. In cancer, kinases are often derailed, kinases are often derailed and can favor tumor cell increase and adaptation. 'We were specifically looking for kinases with unusually high activity. These kinases might be what cancer cells use to grow, adapt and bypass chemotherapy.'
Cordo’ published results of her work, financed by KWF, in the journal Nature Communications. Cordo’: 'We analyzed all kinases in 11 different models, or subtypes of T-ALL. We found a number of kinases already known to be associated with the disease, including LCK and SRC.’ The researchers also discovered an overactive chain reaction lead by the kinases INSR/IGF-1R. Cordo': 'We found that blocking both LCK or SRC and INSR/IGF-1R with two drugs simultaneously was very effective in killing the cancer cells. Even at low concentrations of the drugs, the combination was more effective than either treatment on its own.'
Next steps
The early results show that this new approach for T-ALL provides leads for further research. 'I hope these results inspire other researchers to explore this further.' Cordo’ herself is focusing on a career path outside the laboratory. She started working at EMA, the European Medicines Agency. Here she is helping researchers carry out their work in such a way that innovative medicines can reach patients more quickly. 'Working within two research groups in two organizations, the Máxima and Amsterdam UMC, has taught me how to deal with different people and work cultures. I really like that I can now use that experience combined with my scientific knowledge to help other researchers achieve scientific breakthroughs faster.'