title: Feedback and redundancy in receptor tyrosine kinase signaling: relevance to cancer therapies.
abstract: Mammalian cells have multiple regulatory mechanisms to deal with perturbations in cellular homeostasis, including feedback loops and crosstalk between the major signaling pathways. While these mechanisms are critically required to help cells survive under dynamic physiological circumstances, they also pose an impediment to the effective treatment of cancer. In this review, we describe what has been learned about interactions between receptor tyrosine kinase-dependent signaling pathways, and how this knowledge can be used to design rational and more effective combination therapies for cancer.
authors.affiliation: Division of Molecular Carcinogenesis and Cancer Genomics Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Chong
authors.initials: C
authors.lastname: Sun
authors.affiliation: Division of Molecular Carcinogenesis and Cancer Genomics Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: r.bernards@nki.nl.
authors.forename: René
authors.initials: R
authors.lastname: Bernards
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004359:Drug Therapy, Combination / Q000379:methods; D005246:Feedback; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy*; D009857:Oncogenes / Q000187:drug effects; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D048490:raf Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; C546842:MTOR protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048490:raf Kinases