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Freedom of Information Act Office

IC Directors' Meeting Highlights

March 16, 2006

To: IC Directors
From: Deputy Director, Executive Secretariat
Subject: IC Directors Meeting Highlights—February 23, 2006

Dr. Gottesman announced that Dr. Zerhouni and Dr. Kington were both out of the office and that he would lead the meeting. He also announced that Dr. David Brailer from HHS was unable to attend the meeting this morning.

Discussion Items

I. Trans-NIH Angiogenesis Research Program (TARP)

Dr. Folkman began by discussing some examples of angiogenesis-dependent diseases and the angiogenesis inhibitors approved for clinical use. He provided some astonishing results from using these drugs such as the results that occurred when treating macular degeneration. He also explained that angiogenesis is a unique organizing principal way of thinking of diseases. It is an organizing principle for oncogene-dependence, new platelet biology, metastasis site specificity, new placental physiology, genetic regulation of angiogenesis, and new pharmacology, and scientific collaboration. He quoted from the December 15, 2005 Nature article regarding angiogenesis, “In the next decades, angiogenesis research will change the face of medicine…with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments.”

Dr. Libutti went on to explain more about the actual TARP program. He shared the mission statement which is to:

  • Encourage and facilitate the study of the underlying mechanisms controlling blood vessel growth and development
  • Identify specific targets and to develop therapeutics against pathologic angiogenesis in order to reduce the morbidity due to abnormal blood vessel proliferation in a variety of disease states
  • Better understand the process of angiogenesis and vascularization to improve states of decreased vascularization
  • Encourage and facilitate the study of the processes of lymphangiogenesis
  • Achieve these goals through a multidisciplinary approach, bringing together investigators with varied backgrounds and varied interests

TARP has had several accomplishments thus far, such as organizing and sponsoring a workshop on opportunities for cross discipline collaboration for vascular biology research, establishing a Web site, and convening a panel to review the current angiogenesis portfolio and to offer opinions on new directions and opportunities. At the present there 5 member ICs: NIDDK, NINDS, NHLBI, NEI, and NCI, as well as the Juvenile Diabetes Research Foundation.

Future directions and opportunities for TARP include:

  • Encouraging inter-Institute programs through collaborative initiatives
  • Promoting research in underrepresented areas
  • Fostering collaborative cross-discipline research and training
  • Facilitating scientific review of collaborative multidisciplinary projects
  • Disseminating information via Web site and sponsored Workshops
  • Expediting access to core resources and expanding cores where needed
  • Advocating for the participation of additional Institutes and Centers
  • Facilitating translation of laboratory findings to the clinic

An energized discussion followed regarding the many possibilities and scientific breakthroughs that will be associated with angiogenesis and the collaborations that are occurring with this.

Scientific Presentation

II. Frontiers in Cancer Research: The Cancer Stem Cell and the Tumor Microenvironment

Dr. Niederhuber started by reporting that there were more than 1.3 million new cancer cases in 2005, that there were approximately 1500 deaths due to cancer each and every day, and that the estimated overall cost in 2002 was $171.6 billion. He explained that cancer is a disease of the genome and that it arises from changes within the DNA of our cells during their lifespan. The frontiers in cancer biology are looking at tumor microenvironment, the presence of cancer stem cells, and an inherited predisposition to metastasis. The previous view was that tumors were autonomous cell masses, the progression of which is driven by genetic alterations accumulated over decades—a static process concentrated on changes in cells. However, the current view looks at tumors as “organs” composed of many interdependent cell types that contribute to tumor development and metastasis—a dynamic process that is interactive with its environment.

He then went on to discuss the possible role of cancer stem cells in the proliferation of cancer with the hypothesis that the accumulation of deleterious mutations (genetic alterations) required to establish the cancer phenotype in a given tissue takes place only in cells that already have the capacity for self-renewal. He noted that cancer stem cells are resilient and that they have the following characteristics:

  • Mimic embryonic and adult stem cells
  • Long life-span, relative quiescence
  • Increased telomerase activity enabling mitosis without shortening telomeres
  • Co-segregate DNA strands to preserve genetic information
  • Active DNA-repair capacity
  • Resistance to apoptosis
  • Can regenerate a tumor
  • Have ability to travel to other tissues; do not need to acquire this characteristic
  • Drug resistance not acquired but present
  • Molecular pathways uniquely present in HSCs and CSCs

He concluded by sharing the following in regards to research:

  • Many solid tumors appear to have a population of stem cells partially resistant to chemotherapy
  • Isolating and studying these cells may give us new insights into cancer and therapies
  • NCI's Molecular Targets Development Program has identified over a dozen compounds that show promise in targeting the stem cell transporter ABCG2, which plays a crucial role in multi-drug resistance in numerous cancers.
  • Cyclopamine, which targets the Hedgehog pathway shared by normal stem cells and cancer stem cells, may be an effective agent against cancer stem cells.

III. Other Informational Items

Dr. Gottesman introduced and welcomed the new Deputy Director of NHLBI, Dr. Susan Shurin.

Ann Brewer
cc: OD Senior Staff

This page last reviewed on June 23, 2011

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