Grant: Travel Awards - Institute Community Support

Chronic myeloid leukemia (CML) is a white blood cell cancer that is treated with the chemotherapeutic agent Gleevec (imatinib mesylate, IM). However, only some patients respond to the treatment well while others do not, making cancer care ineffective and therefore warrants further research. Several studies are performed to understand why some patients respond better to Gleevec than others. One focus of the research is directed to the changed metabolic needs of cancer cells. Cancer cells have a high energy demand and use a recycling process called autophagy to survive starvation during chemotherapy resulting in cancer relapse. Autophagy is a process in which cells digest their organelles to reuse nutrients and thus energy. It occurs at low levels in healthy cells but is misused by cancer cells for more energy to fuel rapid growth. Here, we studied how autophagy is deregulated in CML cells compared to healthy individuals and if it could be a useful marker in predicting if a patient will likely respond to Gleevec therapy or not. We identified that key autophagy proteins are higher in CML than normal, such as ATG4, ATG5 and Beclin-1. Further, we found that there are differences in ATG4 and ATG5 levels between patients that respond to Gleevec vs. patients that do not respond. Interestingly, these characteristics are detectable in patients before any therapy and might thus be useful in the future for the prediction of patient's chemotherapy responses. Moreover, we showed that inhibiting autophagy (by decreasing ATG4 protein) makes CML cells sensitive to Gleevec and thus improves how effective the therapy is. These exciting results suggest that a combination of autophagy inhibition and Gleevec treatment might be a valid approach to improve cancer care for patients in the future.