The outcomes of this project confirmed the therapeutic potential of siRNA in combination with designer nanoparticles from lipopolymers as a delivery system. The new therapy we proposed, based on molecular targeting of cancer driving STAT5 gene, has shown promising results in cell models of acute lymphocytic leukemia (ALL). We see similarly successful results in a subset of patient-derived ALL samples as well, but the response was not uniformly positive in all patient samples.

MLL-rearranged (MLL-r) leukemia account for more than 70% of infant ALL (acute lymphoblastic leukemia) cases and 35%-50% of infant AML (acute myeloid leukemia) cases. The status quo to the treatment of MLL-r leukemia can be summarized as: little or no curative effect. The prevalence of these hematological disorders impacting the pediatric patients and the lack of effective treatments highlight the critical need for novel therapeutic strategies.

Immunotherapy has emerged as a powerful approach to treating cancer, but only a subset of patients respond, and the remainder suffer severe side effects without benefiting from the therapy. There is a critical need to understand the factors that limit success of this approach, and to develop strategies to enhance responsiveness. Most immunotherapies involve killing of tumor cells by cells of the immune system called "T cells". For T cells to attack tumors, the tumors must have a protein called MHC on their surface; if tumor cells have no MHC, they cannot be targeted by T cells.

Despite great progress in treating cancer in children, we are still not able to cure all patients, especially those who relapse or do not respond to standard therapy. In T-cell acute lymphoblastic leukemia (T-ALL), children have poor outcomes because of resistance to existing therapies. Therefore, there is an urgent need to identify new treatment strategies. Resistance is often due to outgrowth of cells with changes in their DNA (through genetic alterations) or due to ways of the leukemia cells to adapt epigenetically.

Sarcomas are malignant tumors that affect connective tissues. While generally rare, in patients with DICER1 syndrome, sarcomas are not rare. They primarily arise in the brain and the urogenital tract (e.g. cervix) at a young age, leading to potentially severe consequences. Existing treatments, namely surgery and systemic chemotherapy, do not often lead to positive outcomes. This is due to the inaccessibility of many of the tumors, their inherent chemoresistance and long-term secondary health issues that result from intervention, such as infertility.