title: Locus of fragility in robust breast cancer system.
abstract: Functional heterogeneous redundancy of breast cancer makes this tumor to be robust. Signaling mechanisms which control cancer responses are crucial for controlling robustness. Identification of locus of fragility in cancer represents basic mechanism to target robustness. The goal of this prospect is to present locus of fragility in breast cancer robust system, and how disruption of this locus induces failure of robustness. My recent research show, that locus of fragility in breast cancer cells is suppression of nitric oxide (NO). When it was targeted, dynamics of cancer to generate robustness failed that it blocked cancer cell proliferation dependent on the NO/Rb pathway, blocked cell migration and angiogenesis dependent on the VEGF/PI3K/AKT/NO/ICAM-1 pathway, and induced breast cancer cell apoptosis through the NO/ROCK/FOXO3a signaling pathway. This tiny and trivial perturbation in breast cancer cells such as suppression of NO represents locus of fragility (weakness) and new approach for breast cancer chemotherapy.
authors.affiliation: Department of Cancer Cell Biology, Harvard University, School of Public Health, Boston, Massachusetts 02115, USA. zradisav@hsph.harvard.edu
authors.forename: Ziv
authors.initials: Z
authors.lastname: Radisavljevic
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D043283:Chromosome Fragile Sites; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000037:antagonists & inhibitors
chemical_list: D009569:Nitric Oxide