title: MEK inhibition as a strategy for targeting residual breast cancer cells with low DUSP4 expression.
abstract: Lack of eradication of disseminated breast cancer by chemotherapy is a central clinical problem. Even tumors that show substantial shrinkage after drug treatment frequently relapse and eventually become refractory to all drugs available. The mechanisms underlying this lack of eradication are largely undefined and it is therefore difficult to develop curative strategies using systemic anti-cancer therapy. In a recent article low DUSP4 expression was reported to activate RAS-ERK signaling in residual breast cancer after neoadjuvant chemotherapy. This may be a druggable characteristic because MEK inhibition increases docetaxel sensitivity in a xenograft model.
authors.forename: Sven
authors.initials: S
authors.lastname: Rottenberg
authors.forename: Jos
authors.initials: J
authors.lastname: Jonkers
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D054637:Dual-Specificity Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000517:prevention & control*; D018365:Neoplasm, Residual / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis / Q000235:genetics; D034622:RNA Interference; D043823:Taxoids / Q000494:pharmacology
chemical_list: C517975:AZD 6244; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D043823:Taxoids; D000077143:Docetaxel; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases; C490583:DUSP4 protein, human; D054637:Dual-Specificity Phosphatases; D016283:Proto-Oncogene Proteins p21(ras)