Open Journal Systems

Cover Image

Clinical significance of PARP-1 inhibitors in cancer chemotherapy

Satyakam Singh, Dilip Kumar Makwana, Terrisha Buckley, Arun Agrawal, Srinivas V Koduru, Amit K Tiwari

Abstract


Poly (ADP­ribose) polymerase 1 (PARP-1) protein plays an important role in the repair of single strand breaks (SSBs) in the DNA. This is mediated by base excision repair (BER) of SSBs. PARP-1 inhibition allows accumulation of SSBs and consequently double strand breaks (DSBs). PARP inhibitors disrupt the BER and causes cell damage and death, especially in breast cancer susceptibility          proteins 1 (BRCA 1) or BRCA2­mutated cell in which homologous recombination (HR) pathway is defective. PARP-1 is effective as a single agents in BRCA-1 and BRCA-2 mutated ovarian and breast cancer. In addition, a number of studies have shown beneficial effects with PARP-1 inhibitors in combination with cytotoxic agents that target SSBs, especially in case of triple negative breast cancers (TNBC).  Here we have reviewed potential clinical applications of PARP-1 inhibitors and issues associated with it for successful cancer chemotherapy.

Keywords


BRCA, DNA repair, PARP inhibitors, breast cancer, ovarian cancer

Full Text:

PDF

References


Chambon P, Weill Jd, Mandel P: Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme. Biochem Biophys Res Commun 1963, 11:39-43.

http://dx.doi.org/10.1016/0006-291X(63)90024-X

Audebert M, Salles B, Calsou P: Involvement of poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase III in an alternative route for DNA double-strand breaks rejoining. J Biol Chem 2004, 279:55117-55126.

http://dx.doi.org/10.1074/jbc.M404524200

PMid:15498778

Pieper AA, Verma A, Zhang J, Snyder SH: Poly (ADP-ribose) polymerase, nitric oxide and cell death. Trends Pharmacol Sci 1999, 20:171-181.

http://dx.doi.org/10.1016/S0165-6147(99)01292-4

Shall S, de Murcia G: Poly(ADP-ribose) polymerase-1: what have we learned from the deficient mouse model? Mutat Res 2000, 460:1-15.

http://dx.doi.org/10.1016/S0921-8777(00)00016-1

Hassa PO, Haenni SS, Elser M, Hottiger MO: Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? Microbiol Mol Biol Rev 2006, 70:789-829.

http://dx.doi.org/10.1128/MMBR.00040-05

PMid:16959969 PMCid:PMC1594587

Huber A, Bai P, de Murcia JM, de Murcia G: PARP-1, PARP-2 and ATM in the DNA damage response: functional synergy in mouse development. DNA Repair (Amst) 2004, 3:1103-1108.

http://dx.doi.org/10.1016/j.dnarep.2004.06.002

PMid:15279798

Aguiar RC, Yakushijin Y, Kharbanda S, Salgia R, Fletcher JA, Shipp MA: BAL is a novel risk-related gene in diffuse large B-cell lymphomas that enhances cellular migration. Blood 2000, 96:4328-4334.

PMid:11110709

Liaudet L, Pacher P, Mabley JG, Virag L, Soriano FG, Hasko G, Szabo C: Activation of poly(ADP-Ribose) polymerase-1 is a central mechanism of lipopolysaccharide-induced acute lung inflammation. Am J Respir Crit Care Med 2002, 165:372-377.

http://dx.doi.org/10.1164/ajrccm.165.3.2106050

PMid:11818323

Ma Y, Chen H, He X, Nie H, Hong Y, Sheng C, Wang Q, Xia W, Ying W: NAD+ metabolism and NAD(+)-dependent enzymes: promising therapeutic targets for neurological diseases. Curr Drug Targets 2012, 13:222-229.

http://dx.doi.org/10.2174/138945012799201711

PMid:22204321

Moroni F, Cozzi A, Chiarugi A, Formentini L, Camaioni E, Pellegrini-Giampietro DE, Chen Y, Liang S, Zaleska MM, Gonzales C et al.: Long-lasting neuroprotection and neurological improvement in stroke models with new, potent and brain permeable inhibitors of poly(ADP-ribose) polymerase. Br J Pharmacol 2012, 165:1487-1500.

http://dx.doi.org/10.1111/j.1476-5381.2011.01666.x

PMid:21913897 PMCid:PMC3372732

Szabo G, Liaudet L, Hagl S, Szabo C: Poly(ADP-ribose) polymerase activation in the reperfused myocardium. Cardiovasc Res 2004, 61:471-480.

http://dx.doi.org/10.1016/j.cardiores.2003.09.029

PMid:14962478

Delaney CA, Wang LZ, Kyle S, White AW, Calvert AH, Curtin NJ, Durkacz BW, Hostomsky Z, Newell DR: Potentiation of temozolomide and topotecan growth inhibition and cytotoxicity by novel poly(adenosine diphosphoribose) polymerase inhibitors in a panel of human tumor cell lines. Clin Cancer Res 2000, 6:2860-2867.

PMid:10914735

Miknyoczki SJ, Jones-Bolin S, Pritchard S, Hunter K, Zhao H, Wan W, Ator M, Bihovsky R, Hudkins R, Chatterjee S et al.: Chemopotentiation of temozolomide, irinotecan, and cisplatin activity by CEP-6800, a poly(ADP-ribose) polymerase inhibitor. Mol Cancer Ther 2003, 2:371-382.

PMid:12700281

Tentori L, Graziani G: Chemopotentiation by PARP inhibitors in cancer therapy. Pharmacol Res 2005, 52:25-33.

http://dx.doi.org/10.1016/j.phrs.2005.02.010

PMid:15911331

Tentori L, Leonetti C, Scarsella M, D'Amati G, Vergati M, Portarena I, Xu W, Kalish V, Zupi G, Zhang J, Graziani G: Systemic administration of GPI 15427, a novel poly(ADP-ribose) polymerase-1 inhibitor, increases the antitumor activity of temozolomide against intracranial melanoma, glioma, lymphoma. Clin Cancer Res 2003, 9:5370-5379.

PMid:14614022

Pommier Y: DNA topoisomerase I inhibitors: chemistry, biology, and interfacial inhibition. Chem Rev 2009, 109:2894-2902.

http://dx.doi.org/10.1021/cr900097c

PMid:19476377 PMCid:PMC2707511

Trudeau ME, Crump M, Charpentier D, Yelle L, Bordeleau L, Matthews S, Eisenhauer E: Temozolomide in metastatic breast cancer (MBC): a phase II trial of the National Cancer Institute of Canada - Clinical Trials Group (NCIC-CTG). Ann Oncol 2006, 17:952-956.

http://dx.doi.org/10.1093/annonc/mdl056

PMid:16565212

Rouleau M, Patel A, Hendzel MJ, Kaufmann SH, Poirier GG: PARP inhibition: PARP1 and beyond. Nat Rev Cancer 2010, 10:293-301.

http://dx.doi.org/10.1038/nrc2812

PMid:20200537 PMCid:PMC2910902

Plummer R, Jones C, Middleton M, Wilson R, Evans J, Olsen A, Curtin N, Boddy A, McHugh P, Newell D et al.: Phase I study of the poly(ADP-ribose) polymerase inhibitor, AG014699, in combination with temozolomide in patients with advanced solid tumors. Clin Cancer Res 2008, 14:7917-7923.

http://dx.doi.org/10.1158/1078-0432.CCR-08-1223

PMid:19047122 PMCid:PMC2652879

Kulkarni SS, Singh S, Shah JR, Low WK, Talele TT: Synthesis and SAR optimization of quinazolin-4(3H)-ones as poly(ADP-ribose)polymerase-1 inhibitors. Eur J Med Chem 2012, 50:264-273.

http://dx.doi.org/10.1016/j.ejmech.2012.02.001

PMid:22365563




DOI: http://dx.doi.org/10.14259%2Ftcb.v1i1.63

Refbacks

  • There are currently no refbacks.