title: Intracellular and intercellular signaling networks in cancer initiation, development and precision anti-cancer therapy: RAS acts as contextual signaling hub.
abstract: Cancer initiation and development are increasingly perceived as systems-level phenomena, where intra- and inter-cellular signaling networks of the ecosystem of cancer and stromal cells offer efficient methodologies for outcome prediction and intervention design. Within this framework, RAS emerges as a 'contextual signaling hub', i.e. the final result of RAS activation or inhibition is determined by the signaling network context. Current therapies often 'train' cancer cells shifting them to a novel attractor, which has increased metastatic potential and drug resistance. The few therapy-surviving cancer cells are surrounded by massive cell death triggering a primordial adaptive and reparative general wound healing response. Overall, dynamic analysis of patient- and disease-stage specific intracellular and intercellular signaling networks may open new areas of anticancer therapy using multitarget drugs, drugs combinations, edgetic drugs, as well as help design 'gentler', differentiation and maintenance therapies.
authors.affiliation: Department of Medical Chemistry, Semmelweis University, P.O. Box 2, H-1428 Budapest, Hungary. Electronic address: Csermely.Peter@med.semmelweis-univ.hu.
authors.forename: Peter
authors.initials: P
authors.lastname: Csermely
authors.affiliation: Gut Health and Food Safety Programme, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK; Earlham Institute/TGAC, The Genome Analysis Centre, Norwich Research Park, Norwich NR4 7UH, UK.
authors.forename: Tamás
authors.initials: T
authors.lastname: Korcsmáros
authors.affiliation: Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA; Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D018631:ras Proteins
keywords: Cancer attractors; Cancer stem cells; Combination therapies; N=1 trials; RAS; Signaling networks