Increasing evidence implicates an important role for a variety of bone marrow derived cells (BMDCs) in tumor angiogenesis and metastatic tumor growth. These cells are derived either from the hematopoietic or mesenchymal cell lineage, and they are distinguished, in part, by the expression of the panhematopoietic marker - CD45. Some of these cell populations can colonize tumors perivascularily, and appear to promote angiogenesis and tumor cell proliferation by paracraine mechanisms, whereas others can contribute “directly” to the growth of tumor vessel capillaries or metastases. In this review we focus in particular on the role of hemangiocytes or recruited bone marrow derived circulating cells (RBCCs) in neovascularization, the contribution of VEGFR1+ hematopoietic stem cells and endothelial precursor cells in metastasis, and the involvement of myeloid derived suppressor CD11b+/Gr-1+ cells in the resistance of tumors to certain antiangiogenic drugs, e.g., VEGF blocking antibodies.
Yuval Shaked obtained his Ph.D. (June 2004) in biochemistry from the Department of Neurology at the Hadassah University Hospital, Jerusalem, Israel, where he studied the normal function of the prion protein. Subsequently, he was trained as a postdoctoral fellow in the laboratory of Dr. Robert S. Kerbel, an investigator pioneering in the metronomic chemotherapy treatment strategy for cancer. During his postdoctoral training, he studied circulating endothelial cells and their precursors subset (CEPs) as possible surrogate biomarkers to monitor angiogenesis biologic activity and determine the optimal biological dose of antiangiogenic drugs and treatment strategies. Furthermore, he investigated the contribution of CEPs to tumor angiogenesis and growth following treatment with various anti-cancer drugs including vascular disrupting agents (VDAs) and chemotherapy. Currently, Yuval Shaked is an assistant professor and a senior lecturer in the Department of Molecular Pharmacology at the Rappaport Faculty of Medicine, Technion – Israel Institute of Technology in Israel (August 2008). His laboratory investigates the role of various types of bone marrow-derived cells in tumor angiogenesis and growth of metastases. Yuval Shaked holds the Yigal Allon fellowship given to most promising junior faculty, which is awarded by the Israeli council of higher education. Throughout his academic career he published over 45 peer-reviewed papers, 15 of which as a leading author.
Emile Voest was registered as a medical doctor in 1985. He became board certified as an internist in July 1993, and as a medical oncologist in January 1995. He completed his Ph program on the enhancement of the efficacy of anthracyclines by modulation of iron metabolism in tumor cells in June 1993 (cum laude). In 1994 and 1995, he was a postdoctoral fellow of the Dutch Cancer Society. As a postdoctoral fellow, he joined the laboratory of Dr. Judah Folkman, Children's Hospital, Harvard Medical School, Boston and worked on endogenous inhibitors of angiogenesis. Thereafter, he worked at the Netherlands Cancer Institute in Amsterdam on high dose chemotherapy. In January 1996, he became a staff member of the Department of Medical Oncology at the University Medical Center Utrecht. In January 1997, he was appointed head of the Laboratory of Medical Oncology at the University Medical Centre Utrecht. In November 1999, he became a full professor in Medical Oncology and the head of the department of Medical Oncology at the University Medical Centre Utrecht. In addition, he was the co-director of the Research Institute “Oncology and Developmental Biology” and a board member of the graduate school of Developmental Biology of the Royal Dutch Academy of Sciences until 2006. He is currently the director of the Oncology Research Program of the UMC Utrecht, a board member of the scientific advisory board of the Dutch Cancer Society and serves in a variety of scientific committees and advisory boards. He has 6 patents to his name in the field of angiogenesis and biomarkers. The department of Medical Oncology at the UMC Utrecht has several preclinical and translational research lines including mitotic checkpoints, von Hippel Lindau tumor suppressor gene function and angiogenesis. The angiogenesis program includes the development and validation of biomarkers as predictive factors of therapy, the development of animal models (e.g. zebrafish), and a large early clinical trials program with a focus on antiangiogenic and other targeted therapies. Emile Voest is also heading the phase I program at the UMC Utrecht with a devoted team of nurses, scientists, data managers and clinicians. The preclinical research program and the early clinical trial program are mutually supportive and have a strong interaction.
