Guest Update by Dr. John E. Niederhuber
Angiogenesis Initiative Fueling Collaboration
One of the most exciting new frontiers in cancer research is the increased focus on the tumor microenvironment. A major focus of this work is on the role of angiogenesis, the formation of new blood vessels to provide nutrients and oxygen to sustain the earliest development of a primary cancer or a metastasis. It was approximately 25 years ago that Dr. Judah Folkman first theorized in the pages of the NEJM that tumors needed to grow new blood vessels to fuel their development. Just 2 years ago, bevacizumab (Avastin) became the first agent specifically developed as an angiogenesis inhibitor to be approved by the Food and Drug Administration (FDA) for use in cancer patients to treat metastatic colorectal cancer.
Other FDA-approved anticancer agents - including bortezomib (Velcade) for the treatment of multiple myeloma and sunitinib (Sutent), which was approved just last month for the treatment of gastrointestinal stromal tumors - also have demonstrated the ability to inhibit angiogenesis. In addition, a number of new angiogenesis inhibitors are in development, including several in late-stage clinical trials, and researchers are finding that some already approved chemotherapy drugs, when used more frequently at doses far lower than standard cytotoxic regimens, target the tumor vasculature.
A number of common disease conditions are, as Dr. Folkman put it, angiogenesis dependent, including macular degeneration, atherosclerosis, diabetic retinopathy, and many others. That recognition brought together representatives from five NIH institutes and the Juvenile Diabetes Research Foundation (JDRF) to launch the Trans-Institute Angiogenesis Research Program (TARP) in February 2004.
Just last week, its leaders, which include Dr. Steve Libutti of the Surgery Branch of the NCI Center for Cancer Research (CCR), provided a status report to the directors of all the National Institutes of Health (NIH) institutes and centers. The directors were excited about what they heard, and additional institute leaders indicated their desire to formally join TARP.
The TARP group sponsored a workshop in the spring of 2004 that led to a number of important recommendations, several of which have already been acted upon. In addition to a number of new, crossdisciplinary research collaborations among both extramural and intramural researchers, several new Requests for Applications have been released, including one sponsored by JDRF that has produced approximately 50 awards.
In addition, the NCI intramural program has committed space and resources to establish an angiogenesis core facility that will help validate and develop assays and reagents used in angiogenesis research, as well as develop new assays. A TARP Web site has been established to provide information about funding opportunities for vascular biology and angiogenesis-related research, resources for investigators, educational opportunities, and much more.
In 1990, 198 angiogenesis-related papers were published in peer-reviewed journals. Last year, more than 4,100 were published, and that number will only increase. TARP has the tremendous potential to improve the quality and effectiveness of research in this field by helping to bring together vascular biology and angiogenesis researchers from different disease disciplines; establishing more effective ways for exchanging information, resources, and data; identifying areas of research that may benefit from more intensive study; and helping to train the next generation of researchers. TARP members are beginning to plan the next workshop to discuss state-of-the-art preclinical and clinical research on angiogenesis and vascular biology, and to promote interdisciplinary interactions. It is anticipated that this will be an annual meeting that includes NIH scientists and representatives from academia and industry.
According to one estimate, more than 500 million people stand to benefit from anti- or pro-angiogenesis treatments in the coming decades. Viewed in that light, it's easy to see why there is so much enthusiasm about and interest in this area of investigation. Its promise is great, and our duty is to fund the best science, encourage collaboration, and leverage our resources to fulfill that promise.