title: miRNAs and ovarian cancer: a miRiad of mechanisms to induce cisplatin drug resistance.
abstract: Ovarian cancer is the most aggressive gynecological cancer. One reason for the low 5-year survival rate of under 40% is that ovarian tumors usually acquire resistance to the platinum-based compounds used to treat them. Resistance to one such compound, cisplatin, can arise via numerous mechanisms that can be categorized as pre-, post-, on- or off-target. Pre-target mechanisms prevent accumulation of cisplatin in the cell, on-target mechanisms allow DNA damage to be repaired more efficiently, post-target mechanisms prevent the damage from inducing apoptosis and off-target mechanisms increase resistance via unrelated compensatory mechanisms. miRNAs are short non-coding RNAs that influence cellular function by repressing gene expression. Here we describe how miRNAs can induce cisplatin resistance in ovarian cancer cells via pre-, post-, on- and off-target mechanisms. A better understanding of how miRNAs feed into the mechanisms of drug resistance will inform the rational design of combination therapies for ovarian cancer.
authors.affiliation: a Department of Biological and Medical Sciences, Faculty of Health and Life Sciences , Oxford Brookes University , Oxford , UK.
authors.forename: Priya
authors.initials: P
authors.lastname: Samuel
authors.affiliation: a Department of Biological and Medical Sciences, Faculty of Health and Life Sciences , Oxford Brookes University , Oxford , UK.
authors.forename: Ryan Charles
authors.initials: RC
authors.lastname: Pink
authors.affiliation: a Department of Biological and Medical Sciences, Faculty of Health and Life Sciences , Oxford Brookes University , Oxford , UK.
authors.forename: Susan Ann
authors.initials: SA
authors.lastname: Brooks
authors.affiliation: a Department of Biological and Medical Sciences, Faculty of Health and Life Sciences , Oxford Brookes University , Oxford , UK.
authors.forename: David RaulFrancisco
authors.initials: DR
authors.lastname: Carter
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D004249:DNA Damage / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D002945:Cisplatin
keywords: Carboplatin; chemotherapy; cisplatin; drug resistance; miRNA; microRNA; ovarian; oxaliplatin; platinum; resistant