Scientists at St. Jude Children''s Research Hospital have discovered that the c-Myc gene is essential for tumor development. c-Myc regulates factors necessary for the growth of blood vessels into tumors -- suggesting that c-Myc is a new potential target for anti-angiogenic cancer therapies.
The Myc family of oncogenes (c-Myc, N-Myc, and L-Myc) help control tumor cell growth, differentiation and development. Scientists have long recognized that c-Myc''s positive effect on cell growth can contribute to cancer development. But researchers have also suspected that c-Myc plays additional roles in the progression of malignancy. Cleveland, St. Jude''s Troy Baudino, and their colleagues have discovered such a role: c-Myc is essential for tumor angiogenesis, or the production of capillaries in tumors.
Growing tumors need oxygen and nutrients to survive. Once a tumor''s demand for oxygen and nutrients exceeds what the existing blood vessels can provide, a new vascular network is established (vasculogenesis), and capillaries are formed to meet the tumor''s increasing needs. Since the late 1990s, when the first anti-angiogenic drugs entered clinical trials, scientists have focused on thwarting a tumor''s growth by cutting off its blood supply. By showing that c-Myc is essential for promoting vasculo- and angiogenesis, The St. Jude researchers have uncovered another possible route to attain this goal.
To evaluate the physiological role of c-Myc, Cleveland''s team derived a strain of mice that are deficient in the gene. The c-Myc-deficient mice die as embryos due to cardiac and neural defects, but also display marked defects in vasculogenesis, angiogenesis and the formation of red blood cells. The researchers found that the vascular defects in the c-Myc-deficient mice arise from the mis-expression of intercellular signals that coordinate vasculo- and angiogenesis during development.
The St. Jude investigators went on to show that c-Myc plays a similar role in orchestrating vasculogenesis during tumor formation. The researchers demonstrated that c-Myc-deficient embryonic stem cells have a diminished ability to form tumors in immunocompromised mice, and that the small tumors that sometimes form have dramatically less vasculature. Scientists still need to pinpoint the role of c-Myc in promoting human tumor growth. However, this study presents strong evidence to suggest that the disruption of c-Myc may prove successful as an anti-angiogenic tool in cancer therapy.