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Genes instruct cells to do their jobs through making specific proteins. In our body, all cells store this what-to-do manual in a set of higher-order structures called chromosomes. When chromosomes break off, the broken pieces sometimes exchange their places to build new chromosomes. These errors, known as translocations, could have no effect on our bodies, but in many cases they might cause problems as severe as cancer. Dr. Su's research focuses on learning how chromosomal translocations promote tumor formation in children and young adults, as well as looking for clinically useful approaches to correct their pathogenic activities and cure these deadly diseases.

Dr. Kabanov and colleagues propose an entirely new way to treat medulloblastoma, the most common malignant pediatric brain tumor. Current treatment requires radiation followed by a year of chemotherapy, fails almost half the patients, and can leave survivors with lifelong brain injury. Tiny extracellular vesicles called exosomes produced by a type of immune cell called macrophages were discovered to travel from the bloodstream into brain tumors. Dr. Kabanov will load exosomes with an agonist of Toll-like receptor to reprogram medulloblastoma tumor associated myeloid cells and enhance their tumoricidal properties. If successful, the therapy will improve medulloblastoma treatment by replacing the current radiation and chemotherapy with the one that is less toxic and more effective.

The second year of this grant is funded by and named for the Miracles for Michael Fund, a St. Baldrick's Hero Fund created in memory of Michael Orbany who was diagnosed with medulloblastoma when he was 6 years old. After completing initial treatment, his cancer relapsed within a year and he passed away at the age of nine. Michael had unwavering faith and perseverance, wanting most of all to make others happy. This fund honors his tremendous strength to never ever give up.

The first year of this grant is funded by and named for the Strong & Courageous Hero Fund, established in honor of Jonah. It celebrates his survivorship from medulloblastoma and his goofy, loving, inclusive personality. This fund was inspired by Jonah’s desire to help other kids with cancer and supports research of brain tumors and the multitude of challenges facing survivors post treatment.

Beckwith-Wiedemann Syndrome (BWS) is a cancer predisposition syndrome and patients with BWS have a significantly increased risk of developing hepatoblastomas. The same genetic changes on chromosome 11 that cause BWS are found in 40% of hepatoblastomas. Dr. Kalish has previously shown that noncancerous liver and HB tissue from patients with BWS have distinct molecular signatures, suggesting the events that set up patients with BWS for HB are due to these changes on chromosome 11. Using the largest BWS collection of tissues worldwide, Dr. Kalish and colleagues will study the specific features of BWS and nonBWS liver cells and HB cells to determine how the changes of chromosome 11 lead to HB. Cell models derived from liver tissue will be used to test how these changes cause the transition from normal liver to HB. This work is a critical step in developing targeted therapies for patients with HB.

Children receiving bone marrow transplant can have serious complication such as bloodstream infections and graft versus host disease and some children die of these complications. Alteration of the bacteria in the gut by treatments including antibiotics is an important cause of these complications. In a previous study Dr. Davies and colleagues have tested the use of human milk to help keep gut bacteria healthy in very young children and found that this treatment worked. They are now studying a purified sugar from human milk, 2-FL that can be given easily as a medicine. Dr. Davies will also test a novel rapid urine test and a blood test to assess health of the gut bacteria during the study. Current tests require a stool sample and can take a long time. This trial will generate the data needed to perform a large-scale multi-center randomized clinical trial that will best prove how well this treatment works.

This grant is generously supported by the Rays of Hope Hero Fund which honors the memory of Rayanna Marrero. She was a happy 3-year-old when she was diagnosed with Acute Lymphoblastic Leukemia (ALL). She successfully battled ALL, but a treatment induced secondary cancer claimed her life at age eight. Rayanna had an amazing attitude and loved life. She, like so many kids facing childhood cancer, did not allow it to define who she was. This Hero Fund aspires to give hope to kids fighting cancer through research.

Pediatric Burkitt Lymphoma (BL) arises from errors during immune (B cell) development. Treatment failure is associated with dismal outcomes, and many pediatric BL survivors will suffer long-term toxicities from therapy, highlighting the need to explore opportunities to identify patients who may be cured with less intense therapies. Little is currently known about the biology of pediatric BL and clinical implications of specific mutations. Therefore, systematic analysis of tissue from children treated on clinical trials represents a unique opportunity to gain insights from valuable specimens to inform biologic risk-based chemotherapy and identify potential targeted therapeutic strategies. Dr. Allen will characterize intrinsic and acquired genetic factors that underlie pathogenesis and predict response to therapy in patients with pediatric BL who have completed treatment on COG clinical trials.

This grant is funded by and named for Jack's Pack - We Still Have His Back, a St. Baldrick's Hero Fund. Jack Klein was a ten year old who loved life, laughing and monkeys. During his illness, his community of family and friends near and far rallied around him under the moniker "Jack's Pack". Their slogan was "We have Jack's Back". After Jack succumbed to Burkitt's Lymphoma, his "pack" focused their energy and efforts to funding a cure...just as Jack would have wanted.

Each year, approximately 1000 Americans aged 20 years or younger are diagnosed with acute myeloid leukemia (AML). Currently, even the most effective targeted drug BCL2 inhibitor-venetoclax (VEN) cannot eradicate all leukemia cells. The remaining cells cause disease recurrence and result in a very low overall survival rate for AML patients. In preliminary studies, Dr. Li found that targeting an enzyme called ADSS2 promotes pediatric AML cells sensitivity to VEN induced mitochondrial apoptosis, resulting in a synthetic lethality. This study will ask how ADSS2 preserves AML cells fitness and test the effectiveness of a first-in-class ADSS2 inhibitor combined with VEN or other BCL2 family protein MCL1 inhibitor in models of AML. If successful, this could lead to a clinical trial with potential impact for childhood AML patients.

Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors of infancy. Standard therapies lead to severe toxicities and poor overall survival. Dr. Raabe aims to identify novel therapies to reduce toxicities and improve survival. Dr. Raabe and colleagues found that cancer cells rely on activation of the integrative stress response (ISR) to maintain cell equilibrium and survival. However, if the ISR is activated too intensely or for too long, cells undergo apoptosis and die. Paxalisib and gemcitabine are medications that induce considerable cell stress, further activating the integrative stress response, and extending survival in models of AT/RT. Dr. Raabe is investigating how these medications act together to target cell stress pathways and their impact on survival in models of AT/RT. The findings will translate directly through the International Pacific Pediatric Neuro-Oncology Consortium (PNOC) into a new clinical trial treating children with relapsed or refractory AT/RT.

This grant is named for Hannah’s Heroes, a St. Baldrick’s Hero Fund created in honor of Hannah Meeson and pays tribute to her fight by raising awareness and funding for all childhood cancers because kids like Hannah “are worth fighting for.”

This institution is a member of a research consortium which is being funded by St. Baldrick's: Treehouse Childhood Cancer Project. For a description of this project, see the consortium grant made to the lead institution: University of California, Santa Cruz, Santa Cruz, CA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Treehouse Childhood Cancer Project. For a description of this project, see the consortium grant made to the lead institution: University of California, Santa Cruz, Santa Cruz, CA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Treehouse Childhood Cancer Project. For a description of this project, see the consortium grant made to the lead institution: University of California, Santa Cruz, Santa Cruz, CA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Treehouse Childhood Cancer Project. For a description of this project, see the consortium grant made to the lead institution: University of California, Santa Cruz, Santa Cruz, CA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Treehouse Childhood Cancer Project. For a description of this project, see the consortium grant made to the lead institution: University of California, Santa Cruz, Santa Cruz, CA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Treehouse Childhood Cancer Project. For a description of this project, see the consortium grant made to the lead institution: University of California, Santa Cruz, Santa Cruz, CA.

Analyzing the genetic code of each patient's cancer enables researchers to identify specific errors that fuel the cancer in that patient. While the genetic code of patients in the clinics analyzed, it is currently difficult to analyze each patient in the context of all other patients. The Treehouse Consortium enables real-time sharing of pediatric cancer data generated by studies and clinical trials across the world, uniting data from diverse sources into a compendium of unprecedented scale. This group developed and made available to others methods to compare each child's cancer against over 12,000 childhood and adult tumors to improve treatment decisions. Fund administered by University of California, Santa Cruz.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Precision–based Therapy for Childhood Leukemia. For a description of this project, see the consortium grant made to the lead institution: Dana–Farber Cancer Institute, Boston, MA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Precision–based Therapy for Childhood Leukemia. For a description of this project, see the consortium grant made to the lead institution: Dana–Farber Cancer Institute, Boston, MA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Precision–based Therapy for Childhood Leukemia. For a description of this project, see the consortium grant made to the lead institution: Dana–Farber Cancer Institute, Boston, MA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Precision–based Therapy for Childhood Leukemia. For a description of this project, see the consortium grant made to the lead institution: Dana–Farber Cancer Institute, Boston, MA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Precision–based Therapy for Childhood Leukemia. For a description of this project, see the consortium grant made to the lead institution: Dana–Farber Cancer Institute, Boston, MA.

This institution is a member of a research consortium which is being funded by St. Baldrick's: Precision–based Therapy for Childhood Leukemia. For a description of this project, see the consortium grant made to the lead institution: Dana–Farber Cancer Institute, Boston, MA.