Abstract
Poly [ADP-ribose] polymerase-1 [PARP-1] is a chromatin-bound nuclear enzyme that gets activated by DNA damage. It facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Increased PARP-1 expression is observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. PARP-1 interacts directly and indirectly with various oncogenic proteins and regulates several transcription factors, thereby modulating carcinogenesis. There is a lot of pre-clinical and clinical data supporting the use of PARP-1 inhibitors [PARP-1i] in cancers that express homologous recombination deficiencies like mutations within the BRCA-1/2 genes. Therapeutic inhibition of PARP-1 is therefore perceived as a promising anticancer strategy, and numerous PARP-1i are currently under development and clinical evaluation. Currently, there are 4 FDA-approved PARP-1i products on the market, and a few more are in the last stage of clinical development. All the molecules are non-selective PARP-1i. While giving promising results, PARP-1i have their own disadvantages, like safety problems, resistance, etc. Looking at the success rate of PARP-1i in various solid tumours, there is a need for novel and selective PARP-1i. In this review, we discuss various aspects related to PARP-1i, like recent developments, overcoming resistance, and selectivity criteria of new molecules for potential PARP-1i.
Keywords: Cancer, PARP-1 [Poly [ADP-ribose] polymerase-1], inhibition, olaprib, apoptosis, repair pathway.
[http://dx.doi.org/10.1016/j.jcrpr.2017.07.001]
[http://dx.doi.org/10.1016/j.ejmech.2014.01.018] [PMID: 24607998]
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[http://dx.doi.org/10.2174/1573408016666200316114209]
[http://dx.doi.org/10.1007/s10541-005-0113-4] [PMID: 15823082]
[http://dx.doi.org/10.1186/1741-7015-10-25] [PMID: 22401667]
[http://dx.doi.org/10.1016/j.ceb.2008.03.006] [PMID: 18450439]
[http://dx.doi.org/10.1093/carcin/bgs132] [PMID: 22431722]
[http://dx.doi.org/10.1038/nrm3376] [PMID: 22713970]
[http://dx.doi.org/10.1186/1471-2164-6-139] [PMID: 16202152]
[http://dx.doi.org/10.1016/j.molcel.2008.08.009] [PMID: 18851833]
[http://dx.doi.org/10.1074/jbc.M505408200] [PMID: 16061477]
[http://dx.doi.org/10.3390/biom3010001] [PMID: 24970154]
[http://dx.doi.org/10.1093/nar/26.8.1891] [PMID: 9518481]
[http://dx.doi.org/10.1007/BF00928449] [PMID: 7898482]
[http://dx.doi.org/10.2741/2909] [PMID: 17981777]
[http://dx.doi.org/10.1002/cncr.26576] [PMID: 22614657]
[http://dx.doi.org/10.7150/ijbs.16176] [PMID: 27994514]
[PMID: 21157412]
[PMID: 26483957]
[PMID: 11357144]
[http://dx.doi.org/10.1038/35056049] [PMID: 11256071]
[http://dx.doi.org/10.1124/mol.59.4.657] [PMID: 11259608]
[http://dx.doi.org/10.1038/onc.2014.295] [PMID: 25220415]
[PMID: 24579667]
[http://dx.doi.org/10.1186/bcr2877]
[PMID: 20633699]
[http://dx.doi.org/10.1186/1477-7827-7-143] [PMID: 19961617]
[http://dx.doi.org/10.3390/biom2040524] [PMID: 24970148]
[http://dx.doi.org/10.1111/j.1742-4658.2005.04864.x] [PMID: 16156780]
[http://dx.doi.org/10.1021/jm100012m] [PMID: 20364863]
[http://dx.doi.org/10.1074/jbc.274.33.22932] [PMID: 10438458]
[http://dx.doi.org/10.1021/acs.biochem.7b01022] [PMID: 29327913]
[http://dx.doi.org/10.1017/S146239940500904X] [PMID: 15836799]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-2260] [PMID: 17332279]
[http://dx.doi.org/10.1158/2159-8290.CD-12-0120] [PMID: 22993403]
[http://dx.doi.org/10.1016/j.ejca.2006.01.061] [PMID: 16809031]
[http://dx.doi.org/10.1002/pbc.22141] [PMID: 19533660]
[http://dx.doi.org/10.1136/jclinpath-2012-201088] [PMID: 23486608]
[http://dx.doi.org/10.3390/ijms18102111] [PMID: 28991194]
[http://dx.doi.org/10.1038/nature03443] [PMID: 15829966]
[http://dx.doi.org/10.1038/nature03445] [PMID: 15829967]
[http://dx.doi.org/10.1073/pnas.1009182107] [PMID: 21127267]
[http://dx.doi.org/10.1038/cr.2008.8] [PMID: 18166975]
[http://dx.doi.org/10.1074/jbc.M006520200] [PMID: 11016934]
[http://dx.doi.org/10.1093/nar/gkn771] [PMID: 18981049]
[http://dx.doi.org/10.1038/nrc3185] [PMID: 22237395]
[http://dx.doi.org/10.1021/bi0003442] [PMID: 10858306]
[http://dx.doi.org/10.1038/emboj.2009.206] [PMID: 19629035]
[http://dx.doi.org/10.1074/jbc.M608406200] [PMID: 17428792]
[http://dx.doi.org/10.1016/j.dnarep.2014.09.004] [PMID: 25283336]
[http://dx.doi.org/10.1038/283593a0] [PMID: 6243744]
[http://dx.doi.org/10.1248/bpb1978.5.900] [PMID: 6187912]
[http://dx.doi.org/10.1093/jnci/djh005] [PMID: 14709739]
[http://dx.doi.org/10.4161/cbt.4.7.1909] [PMID: 16082177]
[http://dx.doi.org/10.1111/j.1349-7006.2007.00567.x] [PMID: 17645773]
[http://dx.doi.org/10.2119/molmed.2010.00240] [PMID: 21424107]
[http://dx.doi.org/10.1016/j.bmcl.2013.06.055] [PMID: 23850199]
[http://dx.doi.org/10.1056/NEJMe0903044] [PMID: 19553640]
[http://dx.doi.org/10.1586/17512433.2014.930662] [PMID: 24984781]
[http://dx.doi.org/10.1038/nature14184] [PMID: 25642963]
[http://dx.doi.org/10.3389/fphar.2013.00018] [PMID: 23450678]
[http://dx.doi.org/10.1038/nature14157] [PMID: 25642960]
[http://dx.doi.org/10.1200/JCO.2014.58.8848] [PMID: 25779564]
[http://dx.doi.org/10.1021/acs.jmedchem.6b00055] [PMID: 27416328]
[http://dx.doi.org/10.1093/nar/gkq387] [PMID: 20483915]
[http://dx.doi.org/10.18632/oncotarget.5367] [PMID: 26399274]
[http://dx.doi.org/10.3892/or.2013.2902] [PMID: 24317580]
[http://dx.doi.org/10.1016/j.clon.2014.02.007] [PMID: 24602564]
[http://dx.doi.org/10.3390/molecules21060772] [PMID: 27304949]
[http://dx.doi.org/10.1179/ACB.66.1.2062507] [PMID: 21485757]
[http://dx.doi.org/10.1056/NEJMoa0900212] [PMID: 19553641]
[http://dx.doi.org/10.1016/S0140-6736(10)60893-8] [PMID: 20609468]
[http://dx.doi.org/10.1016/S0140-6736(10)60892-6] [PMID: 20609467]
[http://dx.doi.org/10.1200/JCO.2009.26.9589] [PMID: 20406929]
[http://dx.doi.org/10.1038/s41523-017-0052-4] [PMID: 29238749]
[PMID: 33327923]
[http://dx.doi.org/10.1016/S1470-2045(13)70240-7] [PMID: 23810788]
[http://dx.doi.org/10.1158/1078-0432.CCR-18-0204] [PMID: 29615458]
[http://dx.doi.org/10.1158/0008-5472.CAN-11-3648] [PMID: 22287547]
[http://dx.doi.org/10.18632/aging.103986] [PMID: 33486472]
[http://dx.doi.org/10.1080/01635581.2018.1491607] [PMID: 30273054]
[http://dx.doi.org/10.1002/ptr.6029] [PMID: 29377384]
[http://dx.doi.org/10.1142/S0192415X12500140] [PMID: 22298457]
[http://dx.doi.org/10.2174/156800912799277403] [PMID: 22268386]
[http://dx.doi.org/10.3892/ijmm.22.1.113] [PMID: 18575783]
[http://dx.doi.org/10.1016/j.bmcl.2013.12.048] [PMID: 24388690]
[PMID: 14522929]
[http://dx.doi.org/10.1007/s00018-010-0490-8] [PMID: 20725763]
[PMID: 25750544]
[PMID: 22788767]
[http://dx.doi.org/10.1016/j.mam.2013.01.006] [PMID: 23370117]
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1227] [PMID: 21795476]
[http://dx.doi.org/10.1158/1078-0432.CCR-11-2821] [PMID: 22307137]
[http://dx.doi.org/10.1200/JCO.2005.10.021] [PMID: 15911865]
[http://dx.doi.org/10.1186/bcr3484] [PMID: 24063698]
[http://dx.doi.org/10.1007/s00280-013-2113-1] [PMID: 23423489]
[http://dx.doi.org/10.1016/j.ejca.2007.07.010] [PMID: 17714938]
[http://dx.doi.org/10.1016/j.ejca.2013.05.020] [PMID: 23810467]
[http://dx.doi.org/10.1016/j.ejca.2009.10.021] [PMID: 19926276]
[http://dx.doi.org/10.1093/annonc/mdq322] [PMID: 20643861]
[http://dx.doi.org/10.1517/13543776.2013.768615] [PMID: 23379721]
[PMID: 19743897]
[http://dx.doi.org/10.1517/13543776.12.7.1047]
[http://dx.doi.org/10.1016/0014-5793(93)80673-I] [PMID: 8224196]
[http://dx.doi.org/10.1124/mol.108.048751] [PMID: 18809672]
[http://dx.doi.org/10.4137/BIC.S36679] [PMID: 26997874]
[PMID: 26100884]
[http://dx.doi.org/10.1038/nm.3369] [PMID: 24202391]
[http://dx.doi.org/10.1038/s41571-018-0055-6] [PMID: 29955114]
[http://dx.doi.org/10.1021/cr020010d] [PMID: 12630848]
[PMID: 12649183]
[http://dx.doi.org/10.2174/157489206775246430] [PMID: 18221025]
[http://dx.doi.org/10.1158/0008-5472.CAN-08-2287] [PMID: 19074863]
[http://dx.doi.org/10.1038/nature06633] [PMID: 18264087]
[http://dx.doi.org/10.1038/nature06548] [PMID: 18264088]
[http://dx.doi.org/10.1097/CAD.0000000000000336] [PMID: 26796987]
[http://dx.doi.org/10.3390/cancers9080109] [PMID: 28829366]
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0088] [PMID: 18413725]
[PMID: 18971340]
[PMID: 27708213]
[http://dx.doi.org/10.3390/cancers13040727] [PMID: 33578789]
[http://dx.doi.org/10.1038/s12276-021-00557-3] [PMID: 33487630]
[http://dx.doi.org/10.2147/CMAR.S200524] [PMID: 31191001]
[http://dx.doi.org/10.1016/j.ygyno.2015.12.020] [PMID: 26723501]
[http://dx.doi.org/10.1016/j.phrs.2005.02.013] [PMID: 15911339]