Changes for NCI’s Developmental Therapeutics Program

BETHESDA, Md—Far-reaching changes in the National Cancer Institute’s 43-year-old Developmental Therapeutics Program (DTP) would “enhance the ability to discover new and useful antitumor drugs during the next decade,” according to the report of an NCI committee, which offered a series of recommendations to ensure its vision.

If implemented, the recommendations will “foster the discovery of drugs which are not simply antiproliferative agents, but rather have unique and novel mechanisms of action,” the committee reported. The 18-member Developmental Therapeutics Review Group was headed by Susan Band Horwitz, PhD, professor of molecular pharmacology, Albert Einstein College of Medicine.

Its aim, Dr. Horwitz told the National Cancer Advisory Board, was “to define the future of NCI in the discovery and development of chemical and biological therapies, and, really, to develop a vision and a blueprint for the future of anticancer drug development.”

As part of its plan, the committee members suggested that NCI limit the portion of the DTP budget devoted to research within the Institute to 15%. “What we would like to do is open up all the DTP’s resources to qualified investigators,” Dr. Horwitz said.

The review group also suggested that NCI develop a flexible and rapid response mechanism “to deal with changing research objectives and resource requirements that arise on a month-to-month basis,” and that it prioritize the distribution of DTP resources “for the discovery of novel therapeutics and novel drug discovery technologies, as well as the development of candidate therapeutics.”

Five Recommendations

The committee made five other major recommendations:

NCI should support a program with the explicit goal of finding small molecules that can manipulate the function of all proteins or processes relevant to cancer.

The Institute should undertake a major new interdisciplinary initiative to determine the structure of cellular targets that are potentially relevant to cancer. This initiative should ensure that x-ray crys-tallography is made readily accessible to all oncology investigators.

Further, NCI should participate vigorously in determining “the structure of all proteins encoded in the human genome—alone and in complex with interacting cellular partners—that may be involved in the malignant process.”

NCI should reorganize its program for screening compounds for antitumor activity to ensure responsiveness to changes in science and technology. The committee urged reducing the 60-cell-line screen currently used to just three cell lines.

“However, NCI should establish a network of extramural sites that have expertise in the development of new assays to assess the effects of compounds on the biochemical, cell biological, and tissue physiological parameters that govern cancer cell pathogenesis and pathophysiology,” the report added.

Centers of excellence should be established in a variety of scientific areas. One example cited by the committee was “pharmacology/toxicology core facilities with the technology in place to do state-of-the-art drug metabolism, pharmacokinetics, and drug absorption studies and simulation.” It also advised NCI to develop methods to allow “more accurate a priori determination of the potential of metabolism and/or toxicity.”

Said Dr. Horwitz, “We would like to see a large part of the Developmental Therapeutics Program budget funding centers of excellence.”

NCI should expand the scope of its biologic resources branch by augmenting the categories of biologic reagents currently produced and by developing capabilities for production of recombinant vectors and novel production technologies.