Mucins and tumor resistance to chemotherapeutic drugs.
Epithelial cancer patients not considered eligible for surgical resection frequently benefit from chemotherapy. Chemotherapy is the treatment of cancer with one or combination of cytotoxic or cytostatic drugs. Recent advances in chemotherapy allowed a great number of cancer patients to receive treatment with significant results. Unfortunately, resistance to chemotherapeutic drug treatment is a major challenge for clinicians in the majority of epithelial cancers because it is responsible for the inefficiency of therapies. Mucins belong to a heterogeneous group of large O-glycoproteins that can be either secreted or membrane-bound. Implications of mucins have been described in relation to cancer cell behavior and cell signaling pathways associated with epithelial tumorigenesis. Because of the frequent alteration of the pattern of mucin expression in cancers as well as their structural and functional characteristics, mucins are thought to also be involved in response to therapies. In this report, we review the roles of mucins in chemoresistance and the associated underlying molecular mechanisms (physical barrier, resistance to apoptosis, drug metabolism, cell stemness, epithelial-mesenchymal transition) and discuss the therapeutic tools/strategies and/or prognosis biomarkers for personalized chemotherapy that could be proposed from these studies.
Inserm, UMR837, Jean Pierre Aubert Research Center, Team #5 "Mucins, Epithelial Differentiation and Carcinogenesis", rue Polonovski, 59045 Lille Cedex, France; Université Lille Nord de France, Lille, France; Centre Hospitalier Régional et Universitaire de Lille, Place de Verdun, 59037 Lille Cedex, France. Electronic address: nicolas.jonckheere@inserm.fr.
Nicolas
N
Jonckheere
Inserm, UMR837, Jean Pierre Aubert Research Center, Team #5 "Mucins, Epithelial Differentiation and Carcinogenesis", rue Polonovski, 59045 Lille Cedex, France; Université Lille Nord de France, Lille, France; Centre Hospitalier Régional et Universitaire de Lille, Place de Verdun, 59037 Lille Cedex, France.
Nicolas
N
Skrypek
Inserm, UMR837, Jean Pierre Aubert Research Center, Team #5 "Mucins, Epithelial Differentiation and Carcinogenesis", rue Polonovski, 59045 Lille Cedex, France; Université Lille Nord de France, Lille, France; Centre Hospitalier Régional et Universitaire de Lille, Place de Verdun, 59037 Lille Cedex, France.
Isabelle
I
Van Seuningen
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D009077:Mucins / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D011110:Polymorphism, Genetic
D000970:Antineoplastic Agents; D009077:Mucins
Apoptosis; Cancer; Chemotherapeutic drug; Mucin; Prognosis biomarker; Resistance