Chemical Biology Consortium: Recovery Act Investment Report
Public Health Burden of Cancer
Cancer is the second leading cause of death in the United States after heart disease. In 2009, it is estimated that nearly 1.5 million new cases of invasive cancer will be diagnosed in this country and more than 560,000 people will die of the disease.
The CBC is an integrated network of chemical biologists and molecular oncologists from government, industry, and academia that will address unmet needs in therapeutic oncology by focusing on areas such as "undruggable" targets and under-represented malignancies. An undruggable target is one that is considered promising from a therapeutic perspective but, from a chemical perspective, cannot be targeted currently because of limitations in established approaches to drug discovery. Under-represented malignancies are cancers that, for a number of reasons, have not previously been the focus of specific drug development efforts, e.g., pediatric cancers. The mission of the CBC is to increase the flow of early-stage drug candidates into NCI's drug development pipeline. In fulfilling this mission, CBC participants will:
- Choose "high-risk" targets that are of low interest to pharmaceutical companies.
- Re-engineer investigators' existing assay methods into high-throughput (large-volume) drug screens.
- Develop screening "hits" into lead agents.
- Invite expert medicinal chemists to review data and design optimized analogs.
- Select promising candidates based on established development milestones.
- Promote candidates with targeted activity to the clinic.
The CBC differs from the current NCI drug-discovery model in that the CBC will select targets, actively screen for agents that affect these targets, and optimize the "drug-like" properties of hits, rather than focus on developing new agents submitted by outside investigators.
The CBC drug discovery and development process consists of five distinct stages, from screening through clinical evaluation of candidate drugs. Inherent in each stage are "Stage Gates"—milestones that support the transition of a molecule to the next stage—and guidelines that can be applied consistently across projects to provide critical go/no-go decision points. This approach is essential to NCI's ability to dynamically manage its pipeline and appropriately allocate finite resources. Project data generated by CBC participants will be shared through a communal Web-based bioinformatics database, as these data will be critical for informed scientific decision-making.
CBC and ARRA
ARRA funding is supporting the efforts of the CBC in two major areas:
- Development of a chemical repository for CBC: To increase the probability of identifying agents worthy of further investigation, it is necessary to augment available trans-NIH chemical libraries with chemicals and libraries that can only be obtained from external sources. To address this need, the CBC has received ARRA funding to help build a Small Molecule Repository (SMR). The major operations of the SMR will include the following: 1) identifying and acquiring small molecule compounds; 2) applying a standard regimen for quality-control; 3) handling, storing, and, maintaining the compound collection within established guidelines; 4) distributing compound screening plates (96, 384, and 1536 sample-well formats) to CBC centers; and 5) depositing the chemical structures of acquired compounds into the CBC database. The SMR project will enable the NCI to develop a state of the art repository to support CBC's chemical-screening operation at numerous centers across the United States. It will also lead to the creation of new jobs.(1, 2, 3, 4, 5, 6)
Development of a functional biology workspace for CBC: The CBC will require enterprise-wide software systems to manage data, documents, projects, and project portfolios. The data will be available to team members and the CBC Senior Management Committee to support resource management and scientific decision making.(7)
- HHSN261200800001E N01CO-2008-00001 — SAIC-Frederick, Inc. (MD)
- N02CM62224 — Ash Stevens (MI)
- N02CM62225 — SRI International (CA)
- N02CM62228 — Research Triangle Institute (NC)
- N02CM62223 — Alchem Laboratories Corporation (FL)
- N02CM52209 — Starks Associates, Inc. (NY)
- HHSN261200800001E N01CO-2008-00001 — SAIC-Frederick (MD)