Targeting c-Myc, Ras and IGF Cascade to Treat Cancer and Vascular Disorders
2006; Taylor & Francis; Volume: 5; Issue: 15 Linguagem: Inglês
10.4161/cc.5.15.3138
ISSN1538-4101
AutoresFilomena de Nigris, Maria Luisa Balestrieri, Claudio Napoli,
Tópico(s)Retinoids in leukemia and cellular processes
ResumoAbstractCancer and vascular diseases remain the predominant causes of morbidity and mortality inindustrialized countries worldwide. The course of atherosclerosis with initiation, progression, andcomplication parallels the three stages of carcinogenesis with induction, growth, and invasion of tissue andneoangiogenesis. Within this framework, the oncogene c-Myc and growth factors pathways are acquiringincreasing importance. Insulin-like growth factor-1 (IGF-1) pathway emerges among them for its versatilepleiotropic actions. A number of genes that permit extensive communication between IGF-1-AKT, p53, andmammalian target of rapamycin (mTOR) pathways have been identified. In turn these pathways lead to p53transcriptional program, the forkhead transcriptional programs, autophagy, and translational controls, whichdetermine cell growth or arrest, cell survival or death. The increased understanding of the extensivecommunication and coordination between all these pathways may enable to targeting these events and toprevent neoplastic and vascular diseases. Great effort has been focused on the development of new agentsdesigned to target various steps of c-Myc, Ras, and IGF cascade. However, what have we recently learnedabout their safety and effectiveness? Here, we review the very recent advances in the identification of novelinhibitors as well as antisense oligonuleotides (ASOs) and siRNA that are proving their usefulness inongoing clinical trials both in therms of toxicity and specificity.
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