Novel Synergistic Targets for Combination Therapy in Philadelphia Chromosome-like Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is cancer of the blood and bone marrow and is the most common cause of cancer in children. Different kinds of ALL are caused by different genetic changes within the leukemia cells, and these changes affect how well children respond to chemotherapy. Although most children with ALL can be cured with regular chemotherapy, the Philadelphia chromosome-like (Ph-like) type of ALL is known to be very difficult to cure and often comes back (relapses). Ph-like ALL is now known to be very common, occurring in 15-25% of older children, adolescents, and adults with ALL. More effective (and also less toxic) treatments are clearly needed to cure children with this type of cancer. We have learned that Ph-like ALL is caused by genetic mutations that result in ‘miswired’ signaling networks inside leukemia cells and may be effectively treated by new medications that specifically target these miswired networks. My research aims to discover new therapies to cure children with Ph-like ALL by analyzing genetic data from patient samples. My goal is to find genetic changes specific to this high risk subtype of leukemia that can be targeted with new drugs that will be more effective against leukemia and possibly have fewer side effects on healthy cells in children’s bodies.
Project Goal:
My research project aims to discover new therapies to improve cure rates for children with Ph-like ALL by analyzing genetic data from patients’ leukemia samples with a goal of identifying genes that may be very susceptible to new targeted medicines and then testing combinations of new medicines in Ph-like ALL cell lines and specialized mouse models. I have examined genetic differences in a large number of leukemia samples from children with ALL and have found previously unidentified drug targets. I predict that using drugs against these targets will be more effective against leukemia cells while sparing healthy cells. In this project I will perform laboratory confirmation studies in leukemia cell lines and in patient leukemia cells grown in animal models. The results of my research project will help us develop effective targeted drug combinations to treat and hopefully cure more children with this high-risk leukemia subtype. The overall goal of my studies is to identify genetically-informed ‘precision medicine’ treatments for children, adolescents, and young adults with high-risk leukemias. This innovative approach towards discovering more optimal targeted therapy approaches is also widely applicable to other types of childhood cancers and represents an exciting method for developing precision medicine for children with cancer.
Project Update 2024:
The purpose of this project was to discover new therapies to improve treatment for children with a specific type of leukemia. We went about this by analyzing genetic data from patients’ leukemia samples in order to identify genes that may be more susceptible to new targeted medicines and then testing combinations of these medicines in cell lines and mouse models. Support from this ALSF Young Investigator grant has allowed us to test new drug combinations and perform laboratory confirmation studies in leukemia cell lines and in patient leukemia cells grown in animal models. Our studies during this funding period show that combining drugs that target specific changes identified in leukemia cells was very effective to decrease leukemia and well-tolerated in mouse models. We also found clinically relevant resistant subpopulations of leukemia cells that require specialized drugs to eliminate them, findings which are highly significant for patients. ALSF funding has been vital in helping me make efficient progress in experiments, and has helped us publish our results thus far in major peer-reviewed journals. ALSF support has also allowed me to compete successfully for additional grant funding to help continue to advance our understanding of leukemia biology, and to hopefully cure more children, adolescents, and young adults with this high-risk leukemia subtype. Our approach towards discovering more optimal targeted therapy approaches is also widely applicable to other types of childhood cancers and represents an exciting method for developing precision medicine for children with cancer.
