Strategic Investments in the

Strategic Development of Cancer Interventions

Our Goal Optimize the transfer, development, and delivery of highly effective molecularly targeted drugs and technologies to specifically prevent, detect, diagnose, and treat cancer.

One of NCI's key strategies to accelerate progress against cancer in the next decade is to optimize the development and speed the delivery of new targeted cancer diagnostics, therapies, and preventives to patients. Accomplishing our aggressive but achievable objectives in this area will require a truly seamless national system for taking new cancer drugs and diagnostics from preclinical development through commercialization.

While numerous academic laboratories are focused on cancer drug and biomarker discovery, the lack of a robust system and infrastructure for developing these new technologies means that many will never reach patients. Developing and obtaining regulatory approval for a single new therapeutic drug is estimated to take 10 to15 years at a cost of over $800 million. These barriers have prompted the Nation's pharmaceutical industries to focus their efforts primarily on markets of a billion dollars or more and, given the many types of cancer and the potential for large numbers of molecular targets for each, cancer does not represent a major market for most large pharmaceutical companies. Conversely, the biotechnology industry has embraced the cancer market and currently there are over 1,500 biotechnology companies, many of which are focused on the development of innovative interventions for cancer. Unfortunately, many of these companies do not succeed due to a lack of funding from the capital markets.

Strategically Expanding Ongoing Activities

NCI has critically examined the strategies and actions required to optimize the transfer of potentially paradigm shifting laboratory discoveries into and through development for targeted cancer drugs and technologies, and we have already undertaken specific activities to address some of the barriers. Current NCI investments such as the Cancer Genome Anatomy Project (CGAP), Academic Public-Private Partnership Programs (AP4s), the Specialized Programs of Research Excellence (SPOREs), Rapid Access to Intervention Development (RAID), Rapid Access to Preventive Intervention Development (RAPID), and the cancer Biomedical Informatics Grid (caBIG) are part of an overarching strategy to lower the risks associated with developing new cancer interventions. This strategy will be optimized by continued investments in advanced bioinformatics platforms, cancer imaging, and nanotechnology. (See Advanced Technologies.) All of these initiatives will drive an ever increasing need for a new, more responsive clinical trials system that is focused on the evaluation of targeted, safe agents and devices. (See An Integrated Clinical Trials System.) We will use new resources in Fiscal Year 2006 for strategic expansion of selected ongoing activities. We will:

Expand the number of new drug candidates arising from the National Cooperative Drug Discovery Groups (NCDDG) and the Drug Development Group (DDG).
Expand the RAID and RAPID programs through NCI's scale-up capabilities and increased use of existing resources in cancer and academic medical centers.
Fund up to six AP4s to discover new interventions for understudied malignancies and rapidly translate these discoveries to human clinical trials.

Speeding Development of Molecularly-Based Interventions

To further facilitate the creation of new molecularly-based diagnostics, therapeutics, and preventives and provide critical scientific support for areas such as combination therapies and molecular target discovery and validation, NCI must also make investments in new enterprise initiatives.

Biospecimen Initiative. In an era of exciting discovery about the genomic basis of cancer, researchers have identified lack of access to high quality biospecimens as rate limiting to progress in molecular medicine. To use sophisticated assay methods such as genomic sequencing and protein detection and measurement, a highly reliable source of biospecimens that are linked to validated clinical information is essential. With sufficient funding in Fiscal Year 2006, NCI will develop a pilot resource for an integrated system to collect biospecimen and clinical information and make it easily available to the scientific community. We will:

Provide a standardized system for specimen acquisition, annotation, processing, and storage to support genetic and proteomic research and biomarker discovery and validation.
Establish a state-of-the-art information system to link investigators to specimens and foster exchange of data across the research enterprise via the cancer Biomedical Informatics Grid (caBIG).
Provide a test-bed for broader applications of a new era system for biospecimen banking and clinical information management.

Cancer Genome Analysis Program. Now armed with the genomic code developed through the Human Genome Project, researchers are developing technologies that can rapidly and inexpensively sequence regions of genomic information as they seek to identify the genetic basis of each patient's cancer. For the patient and healthcare provider, this sets the stage for a revolutionary approach to cancer care in the next decade. Identifying the genomic code of patients at risk for cancer or aiding in the classification of cancer by the patterns of genes present in a tumor will bring an era of molecular medicine not yet explored.

The Cancer Genome Anatomy Project (CGAP) has provided the cancer research community with an invaluable source of state-of-the-art technologies, tools, and databases that has contributed significantly to our understanding of key genetic changes in cancerous versus normal cells. This information has provided cancer researchers with early direction in their search for molecularly-based targets for new cancer interventions. NCI will further extend the scale and scope of CGAP through a collaborative program that will systematically investigate and catalogue genetic abnormalities across several tumor types using a variety of approaches including gene re-sequencing and array technologies.

In Fiscal Year 2006, NCI will support the first patient oriented research project aimed at systematically developing genomic data from cancer cells, to set the stage for a large scale program. Specimens will be collected from patients along with highly accurate and protected patient information. The tumor specimens will be carefully prepared for genomic sequencing using the most advanced genomic technology platforms available. In the pilot phase, researchers will search for abnormalities in the genetic code of a limited number of human tumor types. Several types of sequencing technologies will be applied to the same specimens to determine which methods are most efficient and yield the highest quality information. Researchers will also identify patterns of abnormal genes in the tumor specimens and investigate the basis of cancer and the stages of cancer development. With initial success, this project will be expanded to additional types of solid and hematologic tumors.

Sufficient resources in Fiscal Year 2006 will allow NCI to:

Develop a comprehensive database of genomic sequence data from a defined set of human tumor types.
Provide data analysis tools to help researchers begin to efficiently sift through millions of genomic codes to find relevant signals of cancer development.
Develop improved approaches to sequencing technology that will streamline its application into clinical medicine.
Provide new databases that will inform and drive the discovery of new targeted agents for cancer.

Building Capacity for Early Detection and Targeted Treatment

NCI will also apply new resources in Fiscal Year 2006 to strategic initiatives that build capacity for targeted intervention development, to help ensure that the numbers of new targeted drugs and devices, developed and ultimately approved for marketing through the FDA, increase exponentially in the next few years.

Biomarkers for Drug Discovery and Early Detection. Biomarkers include a number of biological molecules such as DNA and proteins, but one of the most promising areas for drug and device discovery and development is the field of proteomics. Recent breakthroughs are enabling scientists to identify patterns of protein markers associated with cancer initiation and progression and with particular cancers. Biomarkers in cancer research hold promise for making "personalized" medicine a reality. They have many potential applications including early diagnostic testing, monitoring response to treatment, detecting metastatic disease, and building "designer" therapies. When sufficiently validated, they will enable scientists to more rationally discover and develop drugs and quickly identify patients that will respond to specific therapeutic interventions. Biomarkers are also integral to new cancer detection strategies. In fact, proteomics may well hold the key to diagnosing cancer early and finding recurrence well before it becomes a threat. With increased resources in Fiscal Year 2006, NCI will develop a new Clinical Proteomics and Biomarker Discovery Program to:

Assess technologies central to biomarker discovery and integrate the best performers into an optimized platform against which new technologies can be tested.
Develop an open source suite of tools to facilitate the standardization of analysis across laboratories and allow meaningful comparison of results.
Establish and make publicly available a comprehensive database for storing the data from various biomarker projects.
Provide a central, virtual source for reagents with quality control and timely access to data on reagent performance and quality.

National Molecular Target Validation and Credentialing Program. Our increasing ability to "interrogate" the human genome to determine both the sequence and functions of genes and gene products is providing the foundation for new screening technologies designed to identify targeted drug candidates. These new technologies range from the use of small chemical probes (chemical genomics) to systems that detect specific pathway effects following perturbation with a candidate agent. These new systems will significantly enhance the amount of information that can be derived in early discovery concerning significant parameters such as toxicity. Another key barrier to capitalizing on the discovery and development of targeted cancer agents is the validation of molecular targets. We know that cancer may offer literally thousands of potential molecular targets, but it is critical that each molecular entity be validated in terms of its potential to become a robust target for the discovery and development of highly effective cancer drugs. With new resources in 2006, NCI will:

Make available to the community enhanced screening systems to better identify targeted agents for cancer.
Establish a pilot program to evaluate target validation strategies such as RNA interference (RNAi) and systems biology.

Streamlining Preclinical Development

Preclinical development of prospective drugs and diagnostic technologies will require enhanced infrastructure including more accurate, predictive, efficacy models; rational processes for selection of lead candidates; and new NCI capabilities for process scale-up, as described above. Often the most difficult phase of the development of cancer therapeutics and diagnostics is the preparation and presentation of the preclinical information required by the FDA to file an investigational new drug application (IND). The preclinical phase can be daunting and expensive, especially for academic investigators with limited resources. NCI will use new resources in Fiscal Year 2006 to provide support for preclinical development. We will:

Establish an integrated preclinical development program that places significant emphasis on new approaches to define the pharmacology, toxicology, distribution, and other significant parameters associated with the administration of small molecules and biologics.
Make available to the community new technologies such as pharmacogenomics and metabolomics as part of a new approach to preclinical development.

Strategic Development of Cancer Interventions Budget Increase Request for Fiscal Year 2006
Expanding ongoing activities Increased number of new drug candidates New interventions for understudied malignancies	$20.00 M
Speeding development of molecularly-based interventions National biospecimen resource Large scale cancer genome analysis program	40.00 M
Building capacity for early detection and targeted treatment Clinical biomarkers discovery & development program National molecular target validation/credentialing program	35.00 M
Streamlining preclinical development Infrastructure for preclinical development Molecular screening technology platforms	22.00 M
Management & Support	2.00 M
Total	$119.00 M

Readily Available Biospecimen Resources Are a Must for Cancer Research

Scientists depend on the availability of high quality biospecimens collected in a standard manner - e.g., blood and tissue samples - from cancer patients, as well as from healthy volunteers, to enable their research. Access to these high quality biospecimens is especially critical in areas such as genomics and proteomics investigations and for:

Investigating normal and malignant tissue microenvironments. (For additional information, see "Understanding the Tumor Microenviroment".)
Clarifying the underlying biological relationships between anti-tumor immune responses and autoimmune responses to immunotherapy. For additional information, see "Understanding the Tumor Microenviroment".)
Identifying and validating biomarkers of precancers for use in cancer screening and early detection. (For additional information, see "Research Network Advances Prevention and Early Detection".)
Developing and validating surrogate molecular endpoints for clinical trials. (For additional information, see "Speeding Agent Development and Biomarker Validation through Clinical Trails".)

NCI has historically supported a large number of "bio-banks," ranging from a few biospecimens in the hands of individual investigators to large collections that are available for broad use by the research community. We must act now to better standardize and coordinate the collection and storage of human biospecimens to allow more widespread and productive use of these precious resources. The collection of fresh tissue samples will be pivotal to genomics/proteomics research. These critical samples must be collected in full compliance with genetic privacy protection and annotated to include as much data as possible about the biospecimen and the case and be broadly available to researchers.

NCI has collaborated with others to develop a model for a national biospecimen network and accompanying database to begin to address the problem of standardization for biospecimens, access, data availability, and privacy protection. The network will be pre-competitive, regulatory-compliant, genetic privacy-protected, standardized, and inclusive. As we move ahead with this initiative, we will work to ensure that the common standards of collection and storage and peer-reviewed availability of specimens, specified by the national concept, are fully integrated into NCI's biospecimen resource banks. This model is in keeping with similar strategies being pursued in other countries such as the United Kingdom and Japan.

An NCI-FDA Partnership Is Paying Big Dividends in Targeted Cancer Drug and Device Development

Despite increased spending on biomedical research and development, there are fewer new medical products reaching consumers than at any time in more than a decade. Our Nation is also facing unprecedented challenges involving affordability and access to currently available treatments for all patients. To address these issues, the U. S. Food and Drug Administration (FDA) and NCI announced, in November 2003, the development of a system for submitting investigational new drug applications (INDs) electronically under NCI's cancer Biomedical Informatics Grid (caBIG) project. This will allow the FDA to review applications faster and get new treatments to patients more quickly and at lower cost. The eventual goal of the caBIG project is to have an entirely electronic system for the submission and evaluation of clinical information for cancer trials. As a first step, NCI and the FDA will work together to build tools that facilitate electronic interaction, focusing in particular on IND applications.

In July of 2004, the FDA created the Office on Oncology Drug Products, which will focus on a strong approach to the drug and therapeutic biologics review process. NCI will work with FDA through this and other mechanisms to develop processes to ensure that positive results are more quickly translated into new diagnostic or treatment options for patients. The formation of the FDA/NCI Interagency Oncology Task Force (IOTF) is one such initiative. This joint agreement will enhance the efficiency of clinical research and scientific evaluation of new cancer medications and allow researchers to share knowledge and resources. The IOTF is currently working to speed progress along the pipeline of targeted cancer interventions by:

Building a cadre of experts in the science of regulatory review of oncology technologies.
Establishing a senior leadership group to triage issues from NCI-supported investigators and consult on regulatory submissions.
Integrating common bioinformatics tools, including platforms for reporting clinical trials and electronic filing of INDs.
Identifying potential clinical endpoints, from areas such as functional imaging and biomarkers, for use in assessing the effectiveness of new agents in clinical trials.
Developing roadmaps for the future regulation of advanced technologies.

Another joint initiative is the Cancer Fellowship Training Program, which will develop a corps of physicians and scientists who are expert in clinical research, the regulatory process, and translation of research breakthroughs to clinical practice. New programs will make various training opportunities available for NCI researchers at the FDA, including training as product reviewers.

Previous Page | Next Page