Investigations into Tumor Angiogenesis

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Angiogenesis (the recruitment and formation of new blood vessels) plays a fundamental role in vessel development in the embryo and placenta during pregnancy. In adults, it is confined mainly to the menstrual cycle and wound healing, and its occurrence otherwise often heralds pathologic states such as tumor development, atherosclerosis, endometriosis, ischemic injury, or macular degeneration. The late Dr. Judah Folkman, founder of the tumor angiogenesis field, demonstrated that tumors cannot grow beyond a minimal size without recruiting new blood vessels. His suggestion that inhibition of such tumor angiogenesis may be an effective and novel means to target tumors has led to a paradigm shift in cancer care. Hundreds of clinical trials worldwide are now testing anti-angiogenic therapeutic strategies.

Considerable basic and translational angiogenesis research is being conducted at the Center of Cancer Systems Biology. A sizable number of members of our team had tight research collaborations with or trained under Dr. Folkman. Among these are Lynn Hlatky, Philip Hahnfeldt, Amir Abdollahi, Giannoula Klement, Nava Almog, Clare Lamont, Abdo Abou-Slaybi, and Kashi Javaherian. Many of the angiogenic initiatives our researchers designed jointly with Dr. Folkman continue at the CCSB, dovetailing with our Center's two primary mandates: to investigate how intercellular interactions and tumor microenvironment modify tumor evolution, and to develop predictive quantitative models of carcinogenesis and metastasis. To pursue these, the CCSB's team of investigators merge several distinct backgrounds in tumor angiogenesis. These include:
i. quantitative and experimental investigations into “metronomic” (low, uniform) dosing as an anti-angiogenic, optimum-maintenance therapy (Hahnfeldt, Klement)
ii. computational modeling of tumor angiogenic carrying capacity and its influence on tumor progression, including the induction of oscillatory behavior and dormancy (Hlatky, Hahnfeldt)
iii. the molecular determinants of angiogenic signaling in tumor dormancy (Almog, Abdollahi)
iv. the role of platelets in tumor angiogenesis and in other pathologic processes (Klement, Abou-Slaybi)
v. pan-genomic implications of the angiogenic switch (Abdollahi, Hlatky, Hahnfeldt)
vi. studies of radiation quality effect on the ability of the host to support tumor angiogenesis (Lamont – with Girdhani)
vii. studies of the broader role of angiogenesis in radiation oncology (Hlatky, Abdollahi)
viii. the study of intrinsic inhibitors of angiogenesis (Javaherian, Abdollahi).

Publications:

A strong body of work on the topic of tumor angiogenesis has been published by researchers currently at the CCSB: