Help Fight Childhood Cancer

对抗儿童癌症

本项目是 IBM 公司主持的 World Community Grid 项目的子项目。

项目状态和成果

Information on the Help Fight Childhood Cancer project may be found on these pages, on the Chiba University Help Fight Childhood Cancer website (Japanese here) and on Chiba Cancer Center's Help Fight Childhood Cancer website (Japanese here). The latest status updates may also be found at this site. To discuss or ask questions about this project, please visit the Help Fight Childhood Cancer Forum.

任务

The mission of the Help Fight Childhood Cancer project is to find drugs that can disable three particular proteins associated with neuroblastoma, one of the most frequently occurring solid tumors in children. Identifying these drugs could potentially make the disease much more curable when combined with chemotherapy treatment.

意义

Neuroblastoma is one of the most common tumors occuring in early childhood and is the most common cause of death in children with solid cancer tumors. If this project is successful, it could dramatically increase the cure rate for neuroblastoma, providing the breakthrough for this disease that has eluded scientists thus far.

方法

Proteins (molecules which are a bound collection of atoms) are the building blocks of all life processes. They also play an important role in the progress of diseases such as cancer.

Scientists have identified three particular proteins involved with neuroblastoma, which if disabled, could make the disease much more curable by conventional methods such as chemotherapy. This project is performing virtual chemistry experiments between these proteins and each of the three million drug candidates that scientists believe could potentially block the proteins involved. A computer program called AutoDock will test if the shape of the protein and shape of each drug candidate fit together and bond in a suitable way to disable the protein.

This work consists of 9 million virtual chemistry experiments, each of which would take hours to perform on a single computer, totaling over 8,000 years of computer time. World Community Grid is performing these computations in parallel and is thus speeding up the effort dramatically. The project is expected to be completed in two years or less.

详细信息

World Community Grid and scientists at Chiba Cancer Center Research Institute and Chiba University are working together to develop novel drugs to treat neuroblastoma, one of the most frequently occurring solid tumors in children.

Neuroblastoma is one of the most frequently occurring solid tumors in children, especially in the first two years of life, when it accounts for 50% of all tumors. Neuroblastoma comprises 6-10% of all childhood cancers, and 15% of cancer deaths in children. It is the most common cause of death in children with solid cancer tumors. The cause of neuroblastoma is unknown, though most physicians believe that it is an accidental cell growth that occurs during normal development of the adrenal glands and sympathetic ganglia.

The clinical hallmark of neuroblastoma is the prospect for cure varying widely depending on age at diagnosis, extent of disease, and tumor biology. A subset of tumors will undergo spontaneous regression while others show relentless progression. Around half of all cases are currently classified as high-risk for disease relapse, with overall survival rates less than 40% despite intensive multimodal therapy. Despite many advances in the past three decades, neuroblastoma has remained an enigmatic challenge to clinical and basic scientists.

The rapid advancement in genetic research on cancer holds great promise for treating neuroblastoma. Genes linked to various cancers have been found, and scientists are currently developing effective therapeutic drugs aimed at some of the important molecular targets.

World Community Grid and The Help Fight Childhood Cancer Project World Community Grid, the Chiba Cancer Center Research Institute, and Chiba University are working together through the Help Fight Childhood Cancer project to develop novel drugs to treat this complex pediatric tumor.

It has been demonstrated repeatedly that the function of a protein molecule - a substance made up of many atoms – is related to its three-dimensional shape. Scientists are able to determine by experiment the shapes of a protein and of a drug separately, but not always for the two together. If scientists knew how a drug molecule interacts with a target protein, chemists could design even better drugs that would be more potent than existing drugs.

To that end, the project's researchers are using computational methods to identify new candidate drugs that have the right shape and chemical characteristics to block three proteins - TrkB, ALK and SCxx, which are expressed at high levels or abnormally mutated in aggressive neuroblastomas. If these proteins are disabled, scientists believe there should be a high cure rate using chemotherapy.

The researchers have prepared a library of three million compounds - or potential drug candidates (called ligands) - and will use World Community Grid to simulate laboratory experiments to test which of these compounds block these proteins. Simulations will be conducted using AutoDock (also used in World Community Grid's FightAIDS@Home and Discovering Dengue Druges – Together projects), a suite of tools that predict how large numbers of different small drug molecules might bind to TrkB, ALK and SCxx, so the best molecules can be found computationally, before they are selected and tested in the laboratory for efficacy against neuroblastoma.

In the absence of World Community Grid, researchers would have to undertake their investigation through individual docking simulations, which would take approximately 8,000 years to complete. With World Community Grid, analysis can be carried out for thousands of drug candidates in parallel, allowing high throughput screening to be conducted. Researchers estimate this will reduce the time required to about 2 years.

This added level of speed and sophistication could potentially enable researchers to identify new drug candidates for neuroblastoma, thereby facilitating discovery of prognostic clues, which are not apparent by human inspection or traditional analysis alone and could advance the fields of cancer biology, drug discovery and therapy planning.

相关链接

• 官方网站上关于对抗儿童癌症的介绍
• 本站论坛的 World Community Grid 项目讨论区