title: Signal persistence and amplification in cancer development and possible, related opportunities for novel therapies.
abstract: Research in cancer biology has been largely driven by experimental approaches whereby discreet inputs are used to assess discreet outputs, for example, gene-knockouts to assess cancer occurrence. However, cancer hallmarks are only rarely, if ever, exclusively dependent on discreet regulatory processes. Rather, cancer-related regulatory factors affect multiple cancer hallmarks. Thus, novel approaches and paradigms are needed for further advances. Signal pathway persistence and amplification, rather than signal pathway activation resulting from an on/off switch, represent emerging paradigms for cancer research, closely related to developmental regulatory paradigms. In this review, we address both mechanisms and effects of signal pathway persistence and amplification in cancer settings; and address the possibility that hyper-activation of pro-proliferative signal pathways in certain cancer settings could be exploited for therapy.
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, United States.
authors.forename: Shea A
authors.initials: SA
authors.lastname: Ford
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, United States; Immunology Program, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States. Electronic address: gblanck@health.usf.edu.
authors.forename: George
authors.initials: G
authors.lastname: Blanck
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D056915:DNA Copy Number Variations; D055808:Drug Discovery; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
keywords: Apoptosis-effector genes; Cancer hallmarks; Cancer therapy; Hyper-activation of proliferative pathways; Signal amplification; Sustained activation