Targeting c-Myc, Ras and IGF cascade to treat cancer and vascular disorders.
Cancer and vascular diseases remain the predominant causes of morbidity and mortality in industrialized countries worldwide. The course of atherosclerosis with initiation, progression, and complication parallels the three stages of carcinogenesis with induction, growth, and invasion of tissue and neoangiogenesis. Within this framework, the oncogene c-Myc and growth factors pathways are acquiring increasing importance. Insulin-like growth factor-1 (IGF-1) pathway emerges among them for its versatile pleiotropic actions. A number of genes that permit extensive communication between IGF-1-AKT, p53, and mammalian target of rapamycin (mTOR) pathways have been identified. In turn these pathways lead to p53 transcriptional program, the forkhead transcriptional programs, autophagy, and translational controls, which determine cell growth or arrest, cell survival or death. The increased understanding of the extensive communication and coordination between all these pathways may enable to targeting these events and to prevent neoplastic and vascular diseases. Great effort has been focused on the development of new agents designed to target various steps of c-Myc, Ras, and IGF cascade. However, what have we recently learned about their safety and effectiveness? Here, we review the very recent advances in the identification of novel inhibitors as well as antisense oligonuleotides (ASOs) and siRNA that are proving their usefulness in ongoing clinical trials both in terms of toxicity and specificity.
de Nigris
Filomena
F
Department of General Pathology, Division of Clinical Pathology and Excellence Research Center on Cardiovascular Diseases, 1st School of Medicine, II University of Naples, Italy.
Balestrieri
Maria Luisa
ML
Napoli
Claudio
C
D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013002:Somatomedins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014652:Vascular Diseases / Q000628:therapy*; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016271:Proto-Oncogene Proteins c-myc; D013002:Somatomedins; D018631:ras Proteins