Dana-Farber Cancer Institute

Dana-Farber Cancer Institute

44 Binney Street

Boston, MA 2115

United States

Molecular Basis of ALK Inhibition Resistance in High-risk Neuroblastoma

Background

Neuroblastoma is an embryonal tumor responsible for 15% of pediatric cancer deaths. Survival rate for high-risk neuroblastoma, which affects the majority of patients, is still dismal despite the use of aggressive therapy. Relapse occurs in over half of patients, with no current prospect for a cure. Therefore, understanding the cause of relapse is critical for enabling the development of effective treatments.

Identification of FDA-approved Drugs that are Selectively Active Against Hematopoietic Stem and Progenitor Cells with Inactivating Mutations of TET2

Leukemia

Background

Targeting CDK12 in Neuroblastoma Cells

Neuroblastoma

Background

Neuroblastoma (NB) is the leading cause of cancer-related death in children. Despite intensive treatment regimens approximately 50-60% of patients with high-risk neuroblastoma will eventually relapse, emphasizing the need for novel treatment approaches.

Control of Medulloblastoma through the Regulation of Tumor Debris

Brain Tumors, Medulloblastoma

Background

Defining Genomic Consequences of Chromothripsis Using a CRISPR-based Chromosome Labeling System

Osteosarcoma

Background

Emerging evidence suggests that many cancers experience episodes of very rapid mutation. One example is a newly discovered mutagenic event called chromothripsis, in which one of the 46 DNA molecules (chromosomes) in the cell is heavily damaged, causing some segments of the chromosome to become scrambled, while others are lost altogether. Chromothripsis has been described in many cancers, but is particularly common in some pediatric cancers including sarcomas and gliomas.

Therapeutic Reactivation of p53 to Overcome Apoptotic Resistance in Pediatric Leukemia

Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML)

p53 is a renowned tumor suppressor gene that is frequently mutated or deleted in cancer, resulting in the development, persistence, and chemoresistance of human cancers. In surveying the broad spectrum of cancers for genetic modification of p53, we have identified a series of pediatric leukemias that maintain expression of wild-type p53 despite the attendant risks to tumor cell survival. We hypothesized that mechanisms other than p53 mutation and deletion could be operational to neutralize p53 activity in these contexts, including negative regulation of p53 by HDM2 and/or HDMX.

Regulation of Tumor Debris Mediated Inflammation as a Therapeutic Modality in Medulloblastoma

Medulloblastoma

Background

Radiation and chemotherapy is the standard for most patients with cancer. The goal is to kill as many of the tumor cells as possible before resistance develops and the tumor stops responding. Our recent work has discovered that the release of the cellular content (cellular debris) of dead tumor cells into the tumor microenvironment provides the necessary factors that stimulate surviving tumor cells to grow.

Novel Nanoscale Phosphoproteomic Discovery of Therapeutic Targets in AML Stem Cells

Leukemia, Acute Myeloid Leukemia (AML)

Dr. Wang has moved and will be continuing his research at City of Hope's Beckman Research Institute in Duarte, CA. http://www.leowanglab.org/

Background

Acute myeloid leukemia (AML) is difficult to treat, relapses easily, and is often fatal. This is largely due to the existence of rare leukemia stem cells (LSCs), which are able to propagate the disease but are resistant to chemotherapy. Developing therapies that specifically target LSCs will improve AML cure rates dramatically.

The Role of DEF and SSU Processome in Neuroblastoma Pathogenesis

Neuroblastoma

Background

Neuroblastoma is the most common solid tumor of childhood, which accounts for 15% of childhood cancer deaths. Changes in the nucleolus and ribosome biogenesis are known to occur in malignant cells, which is due to the key role of the ribosome in cell growth and proliferation. In my graduate work, I have shown that a nucleolar factor Def plays a role in ribosomal RNA processing during zebrafish development as a component of the SSU processome.

Elucidating Mechanisms Driving Renal Medullary Carcinomas to Deliver a Rational Approach to Cancer Directed Therapy

Renal Cell Carcinoma

Background

Through the natural history of patients with sickle cell trait or disease, we have learned that they are at risk of a rare cancer, renal medullary carcinoma. With a very poor prognosis, it is critical that we understand the molecular underpinnings of this disease in order to devise improved therapeutic options. Unfortunately, there are no models available to study this cancer in the laboratory.

Alex's Lemonade Stand Foundation for Childhood Cancer