PARP-1 inhibitors: a novel genetically specific agents for cancer therapy

被引：7
作者：
Cipak, L. [1 ]
Jantova, S. [2 ]
机构：
[1] Slovak Acad Sci, Canc Res Inst, Bratislava, Slovakia
[2] Slovak Tech Univ Bratislava, Fac Chem & Food Technol, Inst Biochem Nutr & Hlth Protect, Bratislava, Slovakia
来源：
NEOPLASMA | 2010年 / 57卷 / 05期
关键词：
PARP-1; inhibitor; BRCA1; BRCA2; DNA repair; synthetic lethality; POLY(ADP-RIBOSE) POLYMERASE-1 INHIBITORS; RESISTANCE-MODIFYING AGENTS; TUMOR-CELL LINES; BIOLOGICAL-PROPERTIES; POTENT INHIBITORS; MUTANT-CELLS; DNA-DAMAGE; ENZYME; REPAIR; SENSITIVITY;
D O I：
10.4149/neo_2010_05_401
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The nuclear poly(ADP-ribose) polymerase-1 (PARP-1) represents an important novel target in cancer therapy. The enzyme is essential for single strand DNA breaks repair via base excision repair pathway. Inhibition of PARP-1 exerts synthetic lethality" effect towards the tumors with defects in DNA repair by homologous recombination, specifically the tumors with mutations in the breast cancer associated BRCA1 and BRCA2 genes. Recent clinical data confirmed the early in vitro studies and suggest that PARP-1 inhibitors could be used not only as chemosensitizers but as well as single agents to selective kill tumors with defective DNA repair by homologous recombination. Such concept of synthetic lethality" for tumors which have lost one DNA repair pathway by targeting a second DNA repair pathway, represents groundbreaking therapeutic strategy. The review highlights our current knowledge and ongoing clinical development/trials of PARP-1 inhibitors.
引用
收藏
页码：401 / 405
页数：5
相关论文
共 38 条
  • [21] Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis, and X-ray cocrystal structure
    Koch, SSC
    Thoresen, LH
    Tikhe, JG
    Maegley, KA
    Almassy, RJ
    Li, JK
    Yu, XH
    Zook, SE
    Kumpf, RA
    Zhang, C
    Boritzki, TJ
    Mansour, RN
    Zhang, KE
    Ekker, A
    Calabrese, CR
    Curtin, NJ
    Kyle, S
    Thomas, HD
    Wang, LZ
    Calvert, AH
    Golding, BT
    Griffin, RJ
    Newell, DR
    Webber, SE
    Hostomsky, Z
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (23) : 4961 - 4974
  • [22] Phthalazinones. Part 1: The design and synthesis of a novel series of potent inhibitors of poly(ADP-ribose)polymerase
    Loh, VM
    Cockcroft, XL
    Dillon, KJ
    Dixon, L
    Drzewiecki, J
    Everlsey, PJ
    Gomez, S
    Hoare, J
    Kerrigan, F
    Matthews, ITW
    Menear, KA
    Martin, NMB
    Newton, RF
    Paul, J
    Smith, GCM
    Vile, J
    Whittle, AJ
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (09) : 2235 - 2238
  • [23] BRCA2-deficient CAPAN-1 cells are extremely sensitive to the inhibition of poly (ADP-Ribose) polymerase
    McCabe, N
    Lord, CJ
    Tutt, ANJ
    Martin, NMB
    Smith, GCM
    Ashworth, A
    [J]. CANCER BIOLOGY & THERAPY, 2005, 4 (09) : 934 - 936
  • [24] Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition
    McCabe, Nuala
    Turner, Nicholas C.
    Lord, Christopher J.
    Kluzek, Katarzyna
    Bialkowska, Aneta
    Swift, Sally
    Giavara, Sabrina
    O'Connor, Mark J.
    Tutt, Andrew N.
    Zdzienicka, Malgorzata Z.
    Smith, Graeme C. M.
    Ashworth, Alan
    [J]. CANCER RESEARCH, 2006, 66 (16) : 8109 - 8115
  • [25] BENZAMIDE DNA INTERACTIONS - DEDUCTIONS FROM BINDING, ENZYME-KINETICS AND FROM X-RAY STRUCTURAL-ANALYSIS OF A 9-ETHYLADENINE-BENZAMIDE ADDUCT
    MCLICK, J
    HAKAM, A
    BAUER, PI
    KUN, E
    ZACHARIAS, DE
    GLUSKER, JP
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1987, 909 (01) : 71 - 83
  • [26] Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors
    Mendes-Pereira, Ana M.
    Martin, Sarah A.
    Brough, Rachel
    McCarthy, Afshan
    Taylor, Jessica R.
    Kim, Jung-Sik
    Waldman, Todd
    Lord, Christopher J.
    Ashworth, Alan
    [J]. EMBO MOLECULAR MEDICINE, 2009, 1 (6-7) : 315 - 322
  • [27] INHIBITORS OF POLY(ADENOSINE DIPHOSPHATE RIBOSE) SYNTHESIS - EFFECT ON OTHER METABOLIC PROCESSES
    MILAM, KM
    CLEAVER, JE
    [J]. SCIENCE, 1984, 223 (4636) : 589 - 591
  • [28] Apoptosis and necrosis following exposure of U937 cells to increasing concentrations of hydrogen peroxide: The effect of the poly(ADP-ribose)polymerase inhibitor 3-aminobenzamide
    Palomba, L
    Sestili, P
    Columbaro, M
    Falcieri, E
    Cantoni, O
    [J]. BIOCHEMICAL PHARMACOLOGY, 1999, 58 (11) : 1743 - 1750
  • [29] High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs
    Rottenberg, Sven
    Jaspers, Janneke E.
    Kersbergen, Ariena
    van der Burg, Eline
    Nygren, Anders O. H.
    Zander, Serge A. L.
    Derksen, Patrick W. B.
    de Bruin, Michiel
    Zevenhoven, John
    Lau, Alan
    Boulter, Robert
    Cranston, Aaron
    O'Connor, Mark J.
    Martin, Niall M. B.
    Borst, Piet
    Jonkers, Jos
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (44) : 17079 - 17084
  • [30] Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers
    Sakai, Wataru
    Swisher, Elizabeth M.
    Karlan, Beth Y.
    Agarwal, Mukesh K.
    Higgins, Jake
    Friedman, Cynthia
    Villegas, Emily
    Jacquemont, Celine
    Farrugia, Daniel J.
    Couch, Fergus J.
    Urban, Nicole
    Taniguchi, Toshiyasu
    [J]. NATURE, 2008, 451 (7182) : 1116 - U9
1234