Advances in Therapeutic Targeting of the DNA Damage Response in Cancer

Overview

Journal DNA Repair (Amst)

Publisher Elsevier

Specialties Biochemistry
Molecular Biology

Date 2018 May 2

PMID 29715575

Citations 25

Authors

Amar Desai

Yan Yan

Stanton L Gerson

Affiliations

Soon will be listed here.

Abstract

The DNA damage response (DDR) is a series of pathways and processes required to repair lesions to DNA. These pathways range from repairing strand breaks to the double helix, damaged bases formed after oxidation or deamination, inaccurate DNA replication resulting in mispaired base alignment, intrastrand crosslinks that trigger cell death, and a plethora of other genomic insults. The DDR is believed to be a critical component of radio and chemoresistance in many cancers as well, with the tumor's ability to repair therapy induced damage being an important tool used to survive traditional chemotherapeutic agents. Here we summarize advances made in specifically targeting DDR proteins in cancer therapy and project on the potential breakthroughs and pitfalls to arise as the field progresses.

Citing Articles

Possible molecular mechanisms underlying the development of atherosclerosis in cancer survivors.

Banerjee P, Rosales J, Chau K, Nguyen M, Kotla S, Lin S Front Cardiovasc Med. 2023; 10:1186679.

PMID: 37332576 PMC: 10272458. DOI: 10.3389/fcvm.2023.1186679.

De-ubiquitination of SAMHD1 by USP7 promotes DNA damage repair to overcome oncogenic stress and affect chemotherapy sensitivity.

Liu J, Zhou T, Dong X, Guo Q, Zheng L, Wang X Oncogene. 2023; 42(22):1843-1856.

PMID: 37081042 PMC: 10238270. DOI: 10.1038/s41388-023-02667-w.

High-throughput screen to identify compounds that prevent or target telomere loss in human cancer cells.

Wilson C, Murnane J NAR Cancer. 2022; 4(4):zcac029.

PMID: 36196242 PMC: 9527662. DOI: 10.1093/narcan/zcac029.

Perspectives of nano-carrier drug delivery systems to overcome cancer drug resistance in the clinics.

Ulldemolins A, Seras-Franzoso J, Andrade F, Rafael D, Abasolo I, Gener P Cancer Drug Resist. 2022; 4(1):44-68.

PMID: 35582007 PMC: 9019183. DOI: 10.20517/cdr.2020.59.

Nanomedicine Strategies for Management of Drug Resistance in Lung Cancer.

Haider M, Elsherbeny A, Pittala V, Consoli V, Ali Alghamdi M, Hussain Z Int J Mol Sci. 2022; 23(3).

PMID: 35163777 PMC: 8836587. DOI: 10.3390/ijms23031853.

References

Golding S, Rosenberg E, Valerie N, Hussaini I, Frigerio M, Cockcroft X . Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther. 2009; 8(10):2894-902. PMC: 2761990. DOI: 10.1158/1535-7163.MCT-09-0519. View

Marra G, Boland C . Hereditary nonpolyposis colorectal cancer: the syndrome, the genes, and historical perspectives. J Natl Cancer Inst. 1995; 87(15):1114-25. DOI: 10.1093/jnci/87.15.1114. View

Fong P, Boss D, Yap T, Tutt A, Wu P, Mergui-Roelvink M . Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009; 361(2):123-34. DOI: 10.1056/NEJMoa0900212. View

Gavande N, VanderVere-Carozza P, Hinshaw H, Jalal S, Sears C, Pawelczak K . DNA repair targeted therapy: The past or future of cancer treatment?. Pharmacol Ther. 2016; 160:65-83. PMC: 4811676. DOI: 10.1016/j.pharmthera.2016.02.003. View

Nickoloff J, Jones D, Lee S, Williamson E, Hromas R . Drugging the Cancers Addicted to DNA Repair. J Natl Cancer Inst. 2017; 109(11). PMC: 5436301. DOI: 10.1093/jnci/djx059. View

Jiricny J . The multifaceted mismatch-repair system. Nat Rev Mol Cell Biol. 2006; 7(5):335-46. DOI: 10.1038/nrm1907. View

Barakat K, Gajewski M, Tuszynski J . DNA polymerase beta (pol β) inhibitors: a comprehensive overview. Drug Discov Today. 2012; 17(15-16):913-20. DOI: 10.1016/j.drudis.2012.04.008. View

Ciszewski W, Tavecchio M, Dastych J, Curtin N . DNA-PK inhibition by NU7441 sensitizes breast cancer cells to ionizing radiation and doxorubicin. Breast Cancer Res Treat. 2013; 143(1):47-55. DOI: 10.1007/s10549-013-2785-6. View

Mehta A, Haber J . Sources of DNA double-strand breaks and models of recombinational DNA repair. Cold Spring Harb Perspect Biol. 2014; 6(9):a016428. PMC: 4142968. DOI: 10.1101/cshperspect.a016428. View

10.

Calvo E, Braiteh F, Von Hoff D, McWilliams R, Becerra C, Galsky M . Phase I Study of CHK1 Inhibitor LY2603618 in Combination with Gemcitabine in Patients with Solid Tumors. Oncology. 2016; 91(5):251-260. DOI: 10.1159/000448621. View

11.

Mao Z, Bozzella M, Seluanov A, Gorbunova V . Comparison of nonhomologous end joining and homologous recombination in human cells. DNA Repair (Amst). 2008; 7(10):1765-71. PMC: 2695993. DOI: 10.1016/j.dnarep.2008.06.018. View

12.

Marteijn J, Lans H, Vermeulen W, Hoeijmakers J . Understanding nucleotide excision repair and its roles in cancer and ageing. Nat Rev Mol Cell Biol. 2014; 15(7):465-81. DOI: 10.1038/nrm3822. View

13.

Fokas E, Prevo R, Pollard J, Reaper P, Charlton P, Cornelissen B . Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012; 3:e441. PMC: 3542617. DOI: 10.1038/cddis.2012.181. View

14.

Alagpulinsa D, Ayyadevara S, Yaccoby S, Shmookler Reis R . A Cyclin-Dependent Kinase Inhibitor, Dinaciclib, Impairs Homologous Recombination and Sensitizes Multiple Myeloma Cells to PARP Inhibition. Mol Cancer Ther. 2016; 15(2):241-50. PMC: 4747838. DOI: 10.1158/1535-7163.MCT-15-0660. View

15.

Wymann M, Zvelebil M, Pirola L, Vanhaesebroeck B, Waterfield M, Panayotou G . Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction. Mol Cell Biol. 1996; 16(4):1722-33. PMC: 231159. DOI: 10.1128/MCB.16.4.1722. View

16.

Takahashi M, Koi M, Balaguer F, Boland C, Goel A . MSH3 mediates sensitization of colorectal cancer cells to cisplatin, oxaliplatin, and a poly(ADP-ribose) polymerase inhibitor. J Biol Chem. 2011; 286(14):12157-65. PMC: 3069420. DOI: 10.1074/jbc.M110.198804. View

17.

Davidson D, Amrein L, Panasci L, Aloyz R . Small Molecules, Inhibitors of DNA-PK, Targeting DNA Repair, and Beyond. Front Pharmacol. 2013; 4:5. PMC: 3560216. DOI: 10.3389/fphar.2013.00005. View

18.

Morgan M, Lawrence T . Molecular Pathways: Overcoming Radiation Resistance by Targeting DNA Damage Response Pathways. Clin Cancer Res. 2015; 21(13):2898-904. PMC: 4494107. DOI: 10.1158/1078-0432.CCR-13-3229. View

19.

Tutt A, Robson M, Garber J, Domchek S, Audeh M, Weitzel J . Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010; 376(9737):235-44. DOI: 10.1016/S0140-6736(10)60892-6. View

20.

Sander J, Joung J . CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol. 2014; 32(4):347-55. PMC: 4022601. DOI: 10.1038/nbt.2842. View