The study of thalidomide effects on fibroblast growth factor receptor biology in the perspective of tumor angiogenesis

Abstract

Embryonic development is a great example of nature s regulatory mechanisms. Cancers are epitome of entropy. Although these two processes apparently belong to two different poles, they share amazing cellular and molecular similarities. Thalidomide is an infamous teratogen, which was capable of revolutionizing the testing methods in modern medicine. Thalidomide gained attention as an anti-inflammatory and anti-angiogenic drug after it was banned from pharmaceutical market in 1960s. As mechanisms of embryonic and cancer development are very similar, any process or agent that affects development is also expected to modulate cancer growth. Thalidomide also started to be recognized for its anti-tumor properties. In an attempt to eliminate the teratogenic properties, analogs of thalidomide are being developed, two of which have been approved by FDA for the treatment of multiple myeloma. Despite the attempts made, the teratogenic virtues of thalidomide prevail in its analogs, lenalidomide and pomalidomide as well. Fibroblast Growth Factor Receptors (FGFR) are Receptor Tyrosine Kinases (RTK) that regulate a variety of physiological processes by transducing signals from extracellular environment to the cytoplasm upon ligand stimulation. Fibroblast growth factor receptors are major proteins indispensable for embryonic growth, angiogenesis and also found to be the culprit behind key steps of carcinogenesis. FGFR gene mutations lead to various developmental disorders including bent bone dysplasia syndrome and apert syndrome(Ornitz and Itoh 2015). Overexpression and/or aberrant activity of FGFR kinase lead to various pathological conditions. newline