Novel Therapy of Heterogeneous B-cell Acute Lymphocytic Leukemia by Targeting Convergent Oncogenic Mediators STATs
B-cell acute lymphoblastic leukemia (B-ALL) is the most common leukemia among children. Although intensive chemotherapy is able to cure most children, approximately 20% of patients will relapse, not respond to most advanced therapy and eventually die. Multiple genetic abnormalities have been identified that cause the disease, but recent studies are highlighting a set of common mediators that are abnormally activated as a result of numerous genetic abnormalities. Diverse abnormalities converge on these mediators and affect the fate of the cancer cells. Addressing these central regulators, rather than various genetic normalities, could be a more effective approach to control a wide range of ALL abnormalities.
We propose that optimal way to achieve this is by using silencer molecules that are able to eradicate these central regulators from the cells. To realize this goal, we will develop and test nanoparticles that can deliver silencer molecules specifically to the cancer cells causing B-ALL in circulation. We plan to design the nanoparticles with the right antibodies to ‘seek’ the cancer cells; once bound and internalized by the cancer cells, the nanoparticles will release the silencer molecules, eradicating the central mediators of cancer growth and eventually the cancer cells. Our studies will create a therapeutic intervention that has the potential to eradicate leukemic cells that arise from different types of genetic abnormalities. Our therapy will have the potential to improve the effectiveness of treatment in high-risk B-ALL patients irrespective of genetic abnormality, preventing relapse and death.