University of California San Francisco

University of California San Francisco

745 Parnassus Ave

San Francisco, CA 94143

United States

Role of CXCR4/CXCL12 in Inducing Chemotherapy Resistance in Pediatric T-Cell Acute Lymphoblastic Leukemia

Leukemia

Characterization of the Role of Chromosome 1p Deletion in MYCN-Amplified Neuroblastoma

Neuroblastoma

Pediatric Developmental Therapeutics Center of Excellence at UCSF

Leukemia, Neuroblastoma, General Pediatric Cancer

UCSF has an active Pediatric Cancer Developmental Therapeutics Program. The goals of the program are:

Blockade of p53 and Aurora A in Therapy Resistant Neuroblastoma

Neuroblastoma

High-risk MYCN-amplified neuroblastoma is typically responsive to therapy at diagnosis, becoming resistant to chemotherapy/radiation at relapse. Mirroring human disease, the well established TH-MYCN mouse model of neuroblastoma, developed in our lab, is responsive to conventional chemotherapy. To cure MYCN-amplified high-risk neuroblastoma, we propose to:

Targeting inhibitory phosphatase signaling in high-risk childhood ALL

Acute Lymphoblastic Leukemia (ALL)

About 25% of childhood B cell lineage acute lymphoblastic leukemias (ALL) carry oncogenic tyrosine kinases (e.g. JAK2/CRLF2, BCR-ABL and FLT3). Tyrosine kinase driven ALL (TKD-ALL) collectively define the group of patients with the highest risk and a high frequency of drug-resistance and relapse in children.

Blockade of MYCN in neuroblastoma

Neuroblastoma

Neuroblastoma is the third most common pediatric cancer. Amplification of MYCN is a strong independent predictor of poor patient outcome. MYCN represents an attractive target for therapy, as it is serves as a genetic marker for subset of high-risk neuroblastoma and it is expressed at relatively low levels in normal tissues. The ability to inhibit MYCN in patients however, presents a formidable challenge. Many proteins active in cancer (kinases) act by adding a phosphate to a target, thereby altering the activity of the modified target.

Investigation of Genetic and Molecular Mechanisms of Second Malignant Neoplasms in a Mouse Model

General Pediatric Cancer, Hodgkin Lymphoma, Osteosarcoma

Second malignant neoplasms (SMNs) are late complications arising after exposure to chemotherapy and radiotherapy, accounting for most of the ~90,000 new cancers that are diagnosed annually in the United States in persons who previously had a histologically distinct malignancy. Unfortunately, the incidence of SMNs is expected to grow as the at-risk population of cancer survivors increases. This prediction has been borne out with the improved survival of pediatric cancer patients over the last few decades and the increasing numbers of SMNs observed in this population.

Long-Term Morbidity in Survivors of Childhood Cancer with Down Syndrome

General Pediatric Cancer

This project will help to identify late toxicities and long-term follow-up needs specific to childhood cancer survivors with Down Syndrome (DS). Children with DS have a higher risk of certain cancers, particularly childhood leukemias. In recent years modified treatment regimens for leukemia patients with DS have been used because of acute toxicities and differences in overall survival. Nurses at the bedside and nurses involved in the care of survivors rely on information about treatment toxicities to help in the care and education of patients with DS and to guide their follow-up care.

131 I-MIBG Imaging and Therapy for Neuroblastoma: Infrastructure Proposal

Neuroblastoma

Neuroblastoma is a highly malignant tumor of children that arises in the peripheral sympathetic nervous system, and spreads widely to bones and bone marrow. The survival of children with metastatic neuroblastoma is less than 40%, despite intensive chemotherapy, radiation and bone marrow transplant. Metaiodobenzylguanidine (MIBG) is a chemical similar in structure to noradrenaline and specifically taken up by neuroblastoma, thus providing a means to detect tumor metastases and to deliver intravenous tumor-targeted radiation by attaching a radioactive iodine molecule.

A Pilot Study of the Feasibility and Acceptability of an Interactive Computerized Symptom Assessment Tool to Assess Disease and Treatment-Related Symptoms Experienced by Children with Cancer

General Pediatric Cancer

The use of Patient Report Outcomes in research and clinical care has increased substantially in recent years. Multiple challenges exist when researchers and clinicians collect symptom data from children. One goal of this research is to determine the feasibility and usefulness of a novel interactive computerized symptom assessment tool (SiSom) to be used in both clinical practice and research. The number and type of symptoms reported by children and their parents using a standardized symptom checklist will be compared to the SiSom system.

Alex's Lemonade Stand Foundation for Childhood Cancer