Message From the DCTD Director

Dr. James H. Doroshow, Director,
NCI Division of Cancer Treatment and Diagnosis

The Division of Cancer Treatment and Diagnosis (DCTD) focuses its activities on developing novel diagnostics and therapies for cancer. DCTD staff members, along with colleagues throughout the National Cancer Institute (NCI), academia, and industry, are working to generate a seamless pipeline of biomarkers and therapeutics that runs the gamut from initial efforts in drug discovery through late-stage clinical trials. New cancer imaging techniques play a critical role in support of this pipeline as advances in image-guided diagnosis and image-guided therapies continue to emerge.

A primary goal of NCI’s DCTD is to decrease the time necessary to bring anticancer drugs and biomarkers to the clinic while enhancing our ability to predict which treatments will be most useful for each patient. At the core of this objective is the implementation of the recommendations of the NCI’s Clinical Trials and Operational Efficiency Working Groups and the Institute of Medicine’s report on the NCI’s Clinical Cooperative Group Program. The implementation process has, to date, resulted in the reorganization of the NCI’s Cooperative Groups into a National Clinical Trials Network comprised of one pediatric and up to four adult clinical trials organizations linked to a common menu of clinical trials; such a menu will make every study available to all participating institutions and practices nationwide. This has been possible because of the initiation of a common data management system for all trials, and centralized patient registration and regulatory support from the NCI’s Cancer Trials Support Unit. Furthermore, in less than two years, the NCI — working in concert with our academic colleagues — has made significant progress in fulfilling a major goal of both the Operational Efficiency and IOM reports, by substantively decreasing the timeline required to activate both early-stage and late-stage clinical trials.

To take advantage of the rapid expansion of our knowledge of the genomic basis for many cancers and the relationship of specific genetic characteristics in tumors to therapeutic efficacy, DCTD has organized a network of molecular characterization laboratories to assist in the development and use of investigational, study-specific biomarkers to improve potential outcomes for patients entered on NCI-supported studies that are carried out across a broad range of diseases. These activities span the range from proof-of-mechanism pharmacodynamic investigations to the evaluation of predictive molecular genetic markers in prospective, randomized trials. The NCI will play an important role in developing analytical standards for the critical assays needed in the development of modern therapeutic molecules, will perform investigational assays, and, as well, will provide training in the conduct of critical correlative studies so that they can be performed at the highest level in academic institutions conducting NCI-supported clinical trials. The overall goal is to develop more trials that attempt to define distinct patient populations within each type of tumor, thereby enhancing the potential for target-based, therapeutic success.

DCTD has also embarked on a major effort to coordinate and enhance NCI’s drug discovery program. To bridge the gap between academic drug discovery and the development of anticancer agents in the clinic, the NCI has reinvigorated the process by which academics, the private sector, and the government can work together to move novel compounds along the entire path from molecule synthesis to target validation, pharmacologic investigation, toxicologic study, formulation, and the conduct of first-in-human trials. The new pipeline for this effort is called NExT (NCI Experimental Therapeutics); it has consolidated all new drug discovery and development efforts within the Division, and provides direct access for extramural scientists to the full range of NCI-supported resources needed to bring new molecules to patients (see http://next.cancer.gov/). Furthermore, the NExT program encompases immunotherapeutic, as well as small molecule, approaches to cancer treatment. DCTD is currently engaged in producing a range of essential immunomodulatory molecules for clinical testing, from a list prioritized by the extramural immunotherapy community, including IL-15 and IL-7. To carry out the effective evaluation of these and other molecules, DCTD established the Cancer Immunotherapy Network, a translational clinical trials group that includes major academic immunotherapy centers across the country. This group has recently embarked on an ambitious program of multisite clinical trials to evaluate several innovative, immunologically-based treatment strategies for cancer.

Finally, in the rapidly-changing world of cancer therapy and diagnosis, DCTD continues to evaluate unmet needs and understudied areas of cancer therapeutics and diagnostics. The box accompanying this message provides a summary of some the areas that we believe will require additional attention and investigative interest by the academic community in coming years. We are dedicated to continue to focus our energies specifically in areas that require enhanced attention to improve the pace of progress.

DCTD Research Interests

Areas of research interest currently underinvestigated in the DCTD portfolio:

• Enhancing Tumor Response to Therapy
  • Target-based drug development
  • Development of combination therapies in clinically relevant models
  • Targeting molecular signaling pathways
  • Reducing toxicity using image-guided interventions to target drug delivery and activation
  • Studies on the beneficial or harmful effects of anticancer agents on unintended targets
  • Development of approaches, including complementary medicine approaches, to improve the therapeutic index of standard and investigational anticancer therapies
  • Discovery and re-discovery of drugs from traditional medicine pharmacopoeia
• Investigations of the Tumor Microenvironment
  • Design and testing of agents that target the tumor microenvironment using clinically relevant models
  • Exploiting the tumor microenvironment’s role in therapy
  • Understanding the dynamic relationship between tumors and cells in the microenvironment
  • Measuring and evaluating the role of the tumor microenvironment in tumor transformations through imaging and other noninvasive methods
• Development of New Methods and Technologies
  • Development of new imaging technologies, including novel hardware, new research interfaces, refinement of image processing, and further development of virtual imaging
  • Validation of imaging as a biomarker, including development of methods to better determine a response to therapy
  • Development of new imaging agents
  • Development and application of diagnostic devices and technologies that support multi-analyte molecular assays
  • Development of integrated lab-on-a-chip diagnostic devices for real-time analysis of biospecimens
  • Methods, mechanisms, and technologies to ensure the availability of clinical specimens for translational research
• Clinical Studies
  • Translational and clinical studies in the following underinvestigated diseases: pancreatic cancer, squamous cell carcinoma of the head and neck, bladder cancer, and sarcoma
  • Validation of the clinical utility of molecular profiles
  • Clinical studies using imaging approaches to characterize disease anatomy, physiology, and molecular biology
  • Validation of the clinical utility of novel, innovative clinical diagnostic devices
  • Development of personalized medicine approaches including the discovery, development, and qualification of biomarkers to define efficacy, toxicity, dosing, and schedule of therapy