Trike & Bike is a community fundraising initiative to support VeloSano. This series of youth bike rides provides a meaningful way for children to learn about fitness, fundraising & philanthropy. 1OO% of every dollar these children raise supports pediatric cancer research at Cleveland Clinic Children’s.

ALL CHILDHOOD CANCERS

Harry Lesmana, MD

Cleveland Clinic Children’s / Pediatric Institute

ALL CHILDHOOD CANCERS

Pediatric Pilot Award

Investigation of Childhood Cancer Predisposition Syndrome

The application of next generation sequencing has expanded our knowledge in the field of hereditary cancer predisposition. Multiple studies demonstrated that approximately 10-18% of all cancers are attributed to germline mutations due to cancer predisposition syndromes. However, a large proportion of pediatric-onset familial cancers remains without a known genetic cause. The primary goal of this study is to establish a clinical registry of systematically collected and validated clinical data from individuals with familial cancer and store their biological materials for genetic studies. We propose to use high throughput sequencing technology, including whole exome and/or whole genome and RNA sequencing, to identify novel genes predisposing to pediatric-onset cancer predisposition syndromes and to identify novel genes and/or genetic variants that influence clinical presentation (disease severity) in individuals with known cancer predisposition syndromes.
Identifying the faulty genes responsible for tumor formation in cancer-prone families makes it possible to offer genetic counseling and testing for at-risk family members, provide information about recurrence risk and inform clinical management through the institution of surveillance aimed at early cancer detection. If an identified genetic variant is determined to dysregulate pathways which would further compromise genetic integrity upon exposure to certain chemotherapeutic agents or radiation, then treatment could potentially be modified to mitigate excess toxicity or the risk for second therapy-induced neoplasms. Finally, the information gained will help us to better understand the pathways driving tumor formation and enable development of novel therapies.

IN OTHER WORDS

The goal of this study is to establish a Data Registry linked to a Biorepository of biological samples to facilitate genomic investigations of familial cancer.

LYMPHOMA

Hrishikesh Mehta

Cleveland Clinic Lerner Research Institute

BLOOD CANCER

Pediatric Pilot Award

Chemoprevention of Pediatric Leukemia Predisposition Syndromes Through Nonsense Suppression

Inherited bone marrow failure syndromes (IBMFS) constitute leukemia predisposition syndromes with a high rate of transformation to acute myeloid leukemia (AML). In children, AML has a 5 year survival rate of ~65%, but the prognosis of AML associated with IBMFS is poorer. Severe congenital neutropenia (SCN) and Shwachman Diamond Syndrome (SDS) are IBMFS with loss of neutrophil production. Over the years better disease management has led to increased survival, however development of AML is now the primary risk factor for death. The poor prognosis of AML makes it imperative to find novel treatment options that can prevent AML in vulnerable populations. I propose a novel approach to target both diseases prior to development of AML by taking advantage of a common factor in both diseases. I propose that suppressing the effect of nonsense mutations can be used to prevent AML. In SCN the nonsense mutations are acquired in the gene encoding the granulocyte colony stimulating factor receptor (CSF3R), while in SDS nonsense mutations make up majority of the germline mutations found in the Shwachman-Bodian-Diamond syndrome gene (SBDS). The result of these nonsense mutations are formation of truncated proteins that result in a pre-leukemic state. I propose that the nonsense mutations can be targeted using a nonsense suppression drug called Ataluren, which allows expression of the full-length neomorphic protein, instead of the truncated protein. Approved in Europe for the amelioration of Duchenne muscular dystrophy, Ataluren has not been evaluated in other conditions.

IN OTHER WORDS

Nonsense mutations result in truncated proteins that promote a pre-leukemic state in some children. Using a small molecule approach to manipulate the cellular protein making machinery to skip the nonsense mutations will promote normal full length protein. This approach will not only prevent development of cancer and treat the underlying disease.

MANY CANCER VARIETIES

Sarah Vij, MD

Cleveland Clinic Glickman Urological & Kidney Institute

MANY CANCER VARIETIES

Harry H. Esbenshade VeloSano Pilot Award

Fertility Potential Preservation in Boys Facing Infertility-Causing Diseases or Treatment Regimens with Testicular Tissue Freezing

Currently, no fertility preservation options are available for pre-pubertal boys who are not yet producing sperm. However, experimental techniques are currently being developed to provide future alternatives for patients that preserve their testicular tissue/cells. In order to take advantage of these and future technologies, patients must harvest and preserve their testicular tissue prior to disease or treatment associated with infertility. This study will harvest testicular tissue from eligible patients prior to undergoing therapy that will impact future fertility. Separate portions of the tissue will be banked for future research use and cryopreserved and maintained for participating patients as a resource for future elective procedures to attempt fertility restoration.

IN OTHER WORDS

Pre-pubescent boys undergoing cancer treatments do not presently have any fertility preservation techniques or therapies available. This study aims to harvest testicular tissue prior to gonadotoxic therapies for future utilization and research regarding future options for fatherhood. Additionally, this study will determine if undergoing testicular tissue cryopreservation reduces distress during and after cancer treatment.