title: Novel mechanisms and approaches to overcome multidrug resistance in the treatment of ovarian cancer.
abstract: Ovarian cancer remains the leading cause of gynecological cancer-related mortality despite the advances in surgical techniques and chemotherapy drugs over the past three decades. Multidrug resistance (MDR) to chemotherapy is the major cause of treatment failure. Previous research has focused mainly on strategies to reverse MDR by targeting the MDR1 gene encoded P-glycoprotein (Pgp) with small molecular compound inhibitors. However, prior Pgp inhibitors have shown very limited clinical success because these agents have relatively low potency and high toxicity. Therefore, identification of more specific and potent new inhibitors would be useful. In addition, emerging evidence suggests that cancer stem cells (CSCs), deregulated non-coding RNA (ncRNA), autophagy, and tumor heterogeneity also contribute significantly to drug sensitivity/resistance in ovarian cancer. This review summarizes these novel mechanisms of MDR and evaluates several new concepts to overcome MDR in the treatment of ovarian cancer. These new strategies include overcoming MDR with more potent and specific Pgp inhibitors, targeting CSCs and ncRNA, modulating autophagy signaling pathway, and targeting tumor heterogeneity.
authors.affiliation: Department of Gynecologic Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450052, People's Republic of China; Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA 02114, United States.
authors.forename: Fang
authors.initials: F
authors.lastname: Ren
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA 02114, United States.
authors.forename: Jacson
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Gynecologic Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450052, People's Republic of China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA 02114, United States.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hornicek
authors.affiliation: Department of Gynecologic Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450052, People's Republic of China. Electronic address: qckan19632012@163.com.
authors.forename: Quancheng
authors.initials: Q
authors.lastname: Kan
authors.affiliation: Department of Gynecologic Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450052, People's Republic of China; Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, MA 02114, United States. Electronic address: zduan@mgh.harvard.edu.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Duan
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D001343:Autophagy / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D022661:RNA, Untranslated / Q000037:antagonists & inhibitors
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D022661:RNA, Untranslated
keywords: Autophagy; Cancer stem cells (CSCs); Multidrug resistance (MDR); Non-coding RNA (ncRNA); Ovarian cancer; Tumor heterogeneity (TH)