Weinberg RA: How cancer arises. Sci Am. 275:62–70. 1996. View Article : Google Scholar

Wooster R and Weber BL: Breast and ovarian cancer. N Engl J Med. 348:2339–2347. 2003. View Article : Google Scholar : PubMed/NCBI

International Agency for Research on Cancer: Cancer Tomorrow. Dataviz. https://gco.iarc.fr/tomorrow/en/dataviz.

Petrucelli N, Daly MB and Pal T: BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. GeneReviews® [Internet]. Adam MP, Feldman J, Mirzaa GM, et al: University of Washington; Seattle, WA: 1993-2025, https://www.ncbi.nlm.nih.gov/books/NBK1247/.

Menendez JA, Folguera-Blasco N, Cuyàs E, Fernández-Arroyo S, Joven J and Alarcón T: Accelerated geroncogenesis in hereditary breast-ovarian cancer syndrome. Oncotarget. 7:11959–11971. 2016. View Article : Google Scholar : PubMed/NCBI

Fantone S, Marzioni D and Tossetta G: NRF2/KEAP1 signaling inhibitors in gynecologic cancers. Expert Rev Anticancer Ther. 24:1191–1194. 2024. View Article : Google Scholar

Pokhriyal R, Hariprasad R, Kumar L and Hariprasad G: Chemotherapy resistance in advanced ovarian cancer patients. Biomark Cancer. 11:1179299X198608152019. View Article : Google Scholar :

Akter S, Rahman MA, Hasan MN, Akhter H, Noor P, Islam R, Shin Y, Rahman MDH, Gazi MS, Huda MN, et al: Recent advances in ovarian cancer: Therapeutic strategies, potential biomarkers and technological improvements. Cells. 11:6502022. View Article : Google Scholar

Xiong N, Wu H and Yu Z: Advancements and challenges in triple-negative breast cancer: A comprehensive review of therapeutic and diagnostic strategies. Front Oncol. 14:14054912024. View Article : Google Scholar : PubMed/NCBI

Yin L, Duan JJ, Bian XW and Yu SC: Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res. 22:612020. View Article : Google Scholar

Campagna R, Pozzi V, Giorgini S, Morichetti D, Goteri G, Sartini D, Serritelli EN and Emanuelli M: Paraoxonase-2 is upregulated in triple negative breast cancer and contributes to tumor progression and chemoresistance. Hum Cell. 36:1108–1119. 2023. View Article : Google Scholar

Le HP, Heyer WD and Liu J: Guardians of the Genome: BRCA2 and its partners. Genes (Basel). 12:12292021. View Article : Google Scholar

Angeli D, Salvi S and Tedaldi G: Genetic predisposition to breast and ovarian cancers: How many and which genes to test? Int J Mol Sci. 21:11282020. View Article : Google Scholar : PubMed/NCBI

Lux MP, Fasching PA and Beckmann MW: Hereditary breast and ovarian cancer: Review and future perspectives. J Mol Med (Berl). 84:16–28. 2006. View Article : Google Scholar

Mekonnen N, Yang H and Shin YK: Homologous recombination deficiency in ovarian, breast, colorectal, pancreatic, non-small cell lung and prostate cancers and the mechanisms of resistance to PARP inhibitors. Front Oncol. 12:8806432022. View Article : Google Scholar

Krejci L, Altmannova V, Spirek M and Zhao X: Homologous recombination and its regulation. Nucleic Acids Res. 40:5795–5818. 2012. View Article : Google Scholar : PubMed/NCBI

Grundy MK, Buckanovich RJ and Bernstein KA: Regulation and pharmacological targeting of RAD51 in cancer. NAR Cancer. 2:zcaa0242020. View Article : Google Scholar : PubMed/NCBI

Nowacka-Zawisza M, Wiśnik E, Wasilewski A, Skowrońska M, Forma E, Bryś M, Różański W and Krajewska WM: Polymorphisms of homologous recombination RAD51, RAD51B, XRCC2 and XRCC3 genes and the risk of prostate cancer. Anal Cell Pathol (Amst). 2015:8286462015.

Wu S, Zhou J, Zhang K, Chen H, Luo M, Lu Y, Sun Y and Chen Y: Molecular mechanisms of PALB2 function and its role in breast cancer management. Front Oncol. 10:3012020. View Article : Google Scholar

Nepomuceno TC, De Gregoriis G, de Oliveira FMB, Suarez-Kurtz G, Monteiro AN and Carvalho MA: The role of PALB2 in the DNA damage response and cancer predisposition. Int J Mol Sci. 18:18862017. View Article : Google Scholar : PubMed/NCBI

Yu X, Jacobs SA, West SC, Ogawa T and Egelman EH: Domain structure and dynamics in the helical filaments formed by RecA and RAD51 on DNA. Proc Natl Acad Sci USA. 98:8419–8424. 2001. View Article : Google Scholar :

Subramanyam S, Ismail M, Bhattacharya I and Spies M: Tyrosine phosphorylation stimulates activity of human RAD51 recombinase through altered nucleoprotein filament dynamics. Proc Natl Acad Sci USA. 113:E6045–E6054. 2016. View Article : Google Scholar :

Aihara H, Ito Y, Kurumizaka H, Yokoyama S and Shibata T: The N-terminal domain of the human RAD51 protein binds DNA: Structure and a DNA binding surface as revealed by NMR. J Mol Biol. 290:495–504. 1999. View Article : Google Scholar

Thomas M, Dubacq C, Rabut E, Lopez BS and Guirouilh-Barbat J: Noncanonical roles of RAD51. Cells. 12:11692022. View Article : Google Scholar

Wiese C, Hinz JM, Tebbs RS, Nham PB, Urbin SS, Collins DW, Thompson LH and Schild D: Disparate requirements for the Walker A and B ATPase motifs of human RAD51D in homologous recombination. Nucleic Acids Res. 34:2833–2843. 2006. View Article : Google Scholar

Elbakry A and Löbrich M: Homologous recombination subpathways: A tangle to resolve. Front Genet. 12:7238472021. View Article : Google Scholar : PubMed/NCBI

Conway AB, Lynch TW, Zhang Y, Fortin GS, Fung CW, Symington LS and Rice PA: Crystal structure of a RAD51 filament. Nat Struct Mol Biol. 11:791–796. 2004. View Article : Google Scholar

Kyriukha Y, Watkins MB, Redington JM, Dastvan R, Uversky VN, Hopkins J, Pozzi N and Korolev S: The PALB2 DNA-binding domain is an intrinsically disordered recombinase. Res Sq [Preprint]. rs.3.rs-3235465. 2023.PubMed/NCBI

Park Y, Zhang F and Andreassen PR: PALB2: The hub of a network of tumor suppressors involved in DNA damage responses. Biochim Biophys Acta. 1846:263–275. 2014.PubMed/NCBI

Sun Y, McCorvie TJ, Yates LA and Zhang X: Structural basis of homologous recombination. Cell Mol Life Sci. 77:3–18. 2020. View Article : Google Scholar

Bleuyard JY, Buisson R, Masson JY and Esashi F: ChAM, a novel motif that mediates PALB2 intrinsic chromatin binding and facilitates DNA repair. EMBO Rep. 13:135–141. 2012. View Article : Google Scholar

Park JY, Singh TR, Nassar N, Zhang F, Freund M, Hanenberg H, Meetei AR and Andreassen PR: Breast cancer-associated missense mutants of the PALB2 WD40 domain, which directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair. Oncogene. 33:4803–4812. 2014. View Article : Google Scholar :

Dray E, Etchin J, Wiese C, Saro D, Williams GJ, Hammel M, Yu X, Galkin VE, Liu D, Tsai MS, et al: Enhancement of the RAD51 recombinase activity by the tumor suppressor PALB2. Nat Struct Mol Biol. 17:1255–1259. 2010. View Article : Google Scholar

Matos-Rodrigues G, Guirouilh-Barbat J, Martini E and Lopez BS: Homologous recombination, cancer and the 'RAD51 paradox'. NAR Cancer. 3:zcab0162021. View Article : Google Scholar

Oliver AW, Swift S, Lord CJ, Ashworth A and Pearl LH: Structural basis for recruitment of BRCA2 by PALB2. EMBO Rep. 10:990–996. 2009. View Article : Google Scholar :

Modesti M, Budzowska M, Baldeyron C, Demmers JA, Ghirlando R and Kanaar R: RAD51AP1 is a structure-specific DNA binding protein that stimulates joint molecule formation during RAD51-mediated homologous recombination. Mol Cell. 28:468–481. 2007. View Article : Google Scholar

Lang SH, Swift SL, White H, Misso K, Kleijnen J and Quek RG: A systematic review of the prevalence of DNA damage response gene mutations in prostate cancer. Int J Oncol. 55:597–616. 2019.

Foo TK and Xia B: BRCA1-dependent and independent recruitment of PALB2-BRCA2-RAD51 in the DNA damage response and cancer. Cancer Res. 82:3191–3197. 2022. View Article : Google Scholar

Bonilla B, Hengel SR, Grundy MK and Bernstein KA: RAD51 gene family structure and function. Annu Rev Genet. 54:25–46. 2020. View Article : Google Scholar :

Wang Z, Jia R, Wang L, Yang Q, Hu X, Fu Q, Zhang X, Li W and Ren Y: The emerging roles of RAD51 in cancer and its potential as a therapeutic target. Front Oncol. 12:9355932022. View Article : Google Scholar

Fantone S, Tossetta G, Cianfruglia L, Frontini A, Armeni T, Procopio AD, Pugnaloni A, Gualtieri AF and Marzioni D: Mechanisms of action of mineral fibres in a placental syncytiotrophoblast model: An in vitro toxicology study. Chem Biol Interact. 390:1108952024. View Article : Google Scholar

Smolarz B, Michalska MM, Samulak D, Romanowicz H and Wójcik L: Polymorphism of DNA repair genes in breast cancer. Oncotarget. 10:527–535. 2019. View Article : Google Scholar

Ma É, Maloisel L, Le Falher L, Guérois R and Coïc É: Rad52 oligomeric N-terminal domain stabilizes RAD51 nucleoprotein filaments and contributes to their protection against Srs2. Cells. 10:14672021. View Article : Google Scholar : PubMed/NCBI

Carver A and Zhang X: RAD51 filament dynamics and its antagonistic modulators. Semin Cell Dev Biol. 113:3–13. 2021. View Article : Google Scholar

Andriuskevicius T, Dubenko A and Makovets S: The inability to disassemble RAD51 nucleoprotein filaments leads to aberrant mitosis and cell death. Biomedicines. 11:14502023. View Article : Google Scholar

Wang X, Zhao X, Yu Z, Fan T, Guo Y, Liang J, Wang Y, Zhan J, Chen G, Zhou C, et al: Rtt105 stimulates RAD51-ssDNA assembly and orchestrates RAD51 and RPA actions to promote homologous recombination repair. Proc Natl Acad Sci USA. 121:e24022621212024. View Article : Google Scholar : PubMed/NCBI

Ma CJ, Gibb B, Kwon Y, Sung P and Greene EC: Protein dynamics of human RPA and RAD51 on ssDNA during assembly and disassembly of the RAD51 filament. Nucleic Acids Res. 45:749–761. 2017. View Article : Google Scholar :

Taylor MRG, Špírek M, Chaurasiya KR, Ward JD, Carzaniga R, Yu X, Egelman EH, Collinson LM, Rueda D, Krejci L and Boulton SJ: RAD51 paralogs remodel pre-synaptic RAD51 filaments to stimulate homologous recombination. Cell. 162:271–286. 2015. View Article : Google Scholar :

Bugreev DV and Mazin AV: Ca2+ activates human homologous recombination protein RAD51 by modulating its ATPase activity. Proc Natl Acad Sci USA. 101:9988–9993. 2004. View Article : Google Scholar

Danilowicz C, Peacock-Villada A, Vlassakis J, Facon A, Feinstein E, Kleckner N and Prentiss M: The differential extension in dsDNA bound to RAD51 filaments may play important roles in homology recognition and strand exchange. Nucleic Acids Res. 42:526–533. 2014. View Article : Google Scholar

Mazin AV, Bornarth CJ, Solinger JA, Heyer WD and Kowalczykowski SC: Rad54 protein is targeted to pairing loci by the RAD51 nucleoprotein filament. Mol Cell. 6:583–592. 2000. View Article : Google Scholar : PubMed/NCBI

Akita M, Girvan P, Špírek M, Novacek J, Rueda D, Prokop Z and Krejci L: Mechanism of BCDX2-mediated RAD51 nucleation on short ssDNA stretches and fork DNA. Nucleic Acids Res. 52:11738–11752. 2024. View Article : Google Scholar : PubMed/NCBI

Yang H, Li Q, Fan J, Holloman W and Pavletich N: The BRCA2 homologue Brh2 nucleates RAD51 filament formation at a dsDNA-ssDNA junction. Nature. 433:653–657. 2005. View Article : Google Scholar

Richardson C: RAD51, genomic stability and tumorigenesis. Cancer Lett. 218:127–139. 2005. View Article : Google Scholar

Liao C, Talluri S, Zhao J, Mu S, Kumar S, Shi J, Buon L, Munshi NC and Shammas MA: RAD51 is implicated in DNA damage, chemoresistance and immune dysregulation in solid tumors. Cancers (Basel). 14:56972022. View Article : Google Scholar : PubMed/NCBI

So A, Dardillac E, Muhammad A, Chailleux C, Sesma-Sanz L, Ragu S, Le Cam E, Canitrot Y, Masson JY, Dupaigne P, et al: RAD51 protects against nonconservative DNA double-strand break repair through a nonenzymatic function. Nucleic Acids Res. 50:2651–2666. 2022. View Article : Google Scholar

So A, Muhammad A, Chailleux C, Sanz L, Ragu S, Cam L, Canitrot Y, Masson J, Dupaigne P, Lopez B and Guirouilh-Barbat J: Mammalian RAD51 prevents non-conservative alternative end-joining and single strand annealing through non-catalytic mechanisms. bioRxiv. https://doi.org/10.1101/768887.

Mladenov E, Staudt C, Soni A, Murmann-Konda T, Siemann-Loekes M and Iliakis G: Strong suppression of gene conversion with increasing DNA double-strand break load delimited by 53BP1 and RAD52. Nucleic Acids Res. 48:1905–1924. 2019. View Article : Google Scholar : PubMed/NCBI

Willis NA, Panday A, Duffey EE and Scully R: RAD51 recruitment and exclusion of non-homologous end joining during homologous recombination at a Tus/Ter mammalian replication fork barrier. PLoS Genet. 14:e10074862018. View Article : Google Scholar :

Gallagher DN, Pham N, Tsai AM, Janto AV, Choi J, Ira G and Haber JE: A RAD51-independent pathway promotes single-strand template repair in gene editing. PLoS Genet. 16:e10086892020. View Article : Google Scholar :

Zhu Z, Kitano T, Morimatsu M, Tanaka A, Morioka R, Lin X, Orino K and Yoshikawa Y: BRCA2 C-Terminal RAD51-binding domain confers resistance to DNA-damaging agents. Int J Mol Sci. 23:40602022. View Article : Google Scholar :

Carreira A and Kowalczykowski SC: Two classes of BRC repeats in BRCA2 promote RAD51 nucleoprotein filament function by distinct mechanisms. Proc Natl Acad Sci USA. 108:10448–10453. 2011. View Article : Google Scholar

Andreassen PR, Seo J, Wiek C and Hanenberg H: Understanding BRCA2 function as a tumor suppressor based on domain-specific activities in DNA damage responses. Genes (Basel). 12:10342021. View Article : Google Scholar : PubMed/NCBI

Sadeghi F, Asgari M, Matloubi M, Ranjbar M, Karkhaneh Yousefi N, Azari T and Zaki-Dizaji M: Molecular contribution of BRCA1 and BRCA2 to genome instability in breast cancer patients: Review of radiosensitivity assays. Biol Proced Online. 22:232020. View Article : Google Scholar

Zhang F, Ma J, Wu J, Ye L, Cai H, Xia B and Yu X: PALB2 links BRCA1 and BRCA2 in the DNA-damage response. Curr Biol. 19:524–529. 2009. View Article : Google Scholar : PubMed/NCBI

Simhadri S, Vincelli G, Huo Y, Misenko S, Foo T, Ahlskog J, Sørensen C, Oakley G, Ganesan S, Bunting S and Xia B: PALB2 connects BRCA1 and BRCA2 in the G2/M checkpoint response. Oncogene. 38:1585–1596. 2018. View Article : Google Scholar

Sy S, Huen M, Zhu Y and Chen J: PALB2 regulates recombinational repair through chromatin association and oligomerization. J Biol Chem. 284:18302–18310. 2009. View Article : Google Scholar : PubMed/NCBI

Song F, Li M, Liu G, Swapna GVT, Daigham NS, Xia B, Montelione GT and Bunting SF: Antiparallel coiled-coil interactions mediate the homodimerization of the DNA damage-repair protein PALB2. Biochemistry. 57:6581–6591. 2018. View Article : Google Scholar

Buisson R and Masson JY: PALB2 self-interaction controls homologous recombination. Nucleic Acids Res. 40:10312–10323. 2012. View Article : Google Scholar

Buisson R, Niraj J, Pauty J, Maity R, Zhao W, Coulombe Y, Sung P and Masson J: Breast cancer proteins PALB2 and BRCA2 stimulate polymerase η in recombination-associated DNA synthesis at blocked replication forks. Cell Rep. 6:553–564. 2014. View Article : Google Scholar

Luijsterburg MS, Typas D, Caron MC, Wiegant WW, Van Den Heuvel D, Boonen RA, Couturier AM, Mullenders LH, Masson JY and Van Attikum H: A PALB2-interacting domain in RNF168 couples homologous recombination to DNA break-induced chromatin ubiquitylation. ELife. 6:e209222017. View Article : Google Scholar :

Krais JJ, Wang Y, Patel P, Basu J, Bernhardy AJ and Johnson N: RNF168-mediated localization of BARD1 recruits the BRCA1-PALB2 complex to DNA damage. Nat Commun. 12:50162021. View Article : Google Scholar : PubMed/NCBI

Pauty J, Rodrigue A, Couturier A, Buisson R and Masson JY: Exploring the roles of PALB2 at the crossroads of DNA repair and cancer. Biochem J. 460:331–342. 2014. View Article : Google Scholar : PubMed/NCBI

Ducy M, Sesma-Sanz L, Guitton-Sert L, Lashgari A, Gao Y, Brahiti N, Rodrigue A, Margaillan G, Caron MC, Côté J, et al: The tumor suppressor PALB2: Inside out. Trends Biochem Sci. 44:226–240. 2019. View Article : Google Scholar : PubMed/NCBI

Uemura M, Ochiai K, Morimatsu M, Michishita M, Onozawa E, Azakami D, Uno Y, Yoshikawa Y, Sasaki T, Watanabe M and Omi T: The canine RAD51 mutation leads to the attenuation of interaction with PALB2. Vet Comp Oncol. 18:247–255. 2020. View Article : Google Scholar

Prakash R, Zhang Y, Feng W and Jasin M: Homologous recombination and human health: The roles of BRCA1, BRCA2 and associated proteins. Cold Spring Harb Perspect Biol. 7:a0166002015. View Article : Google Scholar

Zhao W, Steinfeld JB, Liang F, Chen X, Maranon DG, Jian Ma C, Kwon Y, Rao T, Wang W, Sheng C, et al: BRCA1-BARD1 promotes RAD51-mediated homologous DNA pairing. Nature. 550:360–365. 2017. View Article : Google Scholar

Saxena S, Dixit S, Somyajit K and Nagaraju G: ATR signaling uncouples the role of RAD51 paralogs in homologous recombination and replication stress response. Cell Rep. 29:551–559.e4. 2019. View Article : Google Scholar : PubMed/NCBI

Berti M, Teloni F, Mijic S, Ursich S, Fuchs J, Palumbieri MD, Krietsch J, Schmid JA, Garcin EB, Gon S, et al: Sequential role of RAD51 paralog complexes in replication fork remodeling and restart. Nat Commun. 11:35312020. View Article : Google Scholar

Hanenberg H and Andreassen PR: PALB2 (partner and localizer of BRCA2). Atlas Genet Cytogenet Oncol Haematol. 22:484–490. 2018.PubMed/NCBI

Michl J, Zimmer J and Tarsounas M: Interplay between Fanconi anemia and homologous recombination pathways in genome integrity. EMBO J. 35:909–923. 2016. View Article : Google Scholar :

Park D, Bergin SM, Jones D, Ru P, Koivisto CS, Jeon YJ, Sizemore GM, Kladney RD, Hadjis A, Shakya R and Ludwig T: Ablation of the BRCA1-PALB2 interaction phenocopies fanconi anemia in mice. Cancer Res. 80:4172–4184. 2020. View Article : Google Scholar

Schwarz B, Friedl AA, Girst S, Dollinger G and Reindl J: Nanoscopic analysis of 53BP1, BRCA1 and RAD51 reveals new insights in temporal progression of DNA-repair and pathway choice. Mutat Res. 816-818:1116752019. View Article : Google Scholar : PubMed/NCBI

Isono M, Niimi A, Oike T, Hagiwara Y, Sato H, Sekine R, Yoshida Y, Isobe SY, Obuse C, Nishi R, et al: BRCA1 directs the repair pathway to homologous recombination by promoting 53BP1 dephosphorylation. Cell Rep. 18:520–532. 2017. View Article : Google Scholar

Malewicz M: The role of 53BP1 protein in homology-directed DNA repair: Things get a bit complicated. Cell Death Differ. 23:1902–1903. 2016. View Article : Google Scholar

Ochs F, Somyajit K, Altmeyer M, Rask MB, Lukas J and Lukas C: 53BP1 fosters fidelity of homology-directed DNA repair. Nat Struct Mol Biol. 23:714–721. 2016. View Article : Google Scholar

Swift ML, Beishline K, Flashner S and Azizkhan-Clifford J: DSB repair pathway choice is regulated by recruitment of 53BP1 through cell cycle-dependent regulation of Sp1. Cell Rep. 34:1088402021. View Article : Google Scholar

Mohseni-Salehi FS, Zare-Mirakabad F, Sadeghi M and Ghafouri-Fard S: A stochastic model of DNA double-strand breaks repair throughout the cell cycle. Bull Math Biol. 82:112020. View Article : Google Scholar

Roy U and Greene EC: The role of the Rad55-Rad57 complex in DNA repair. Genes (Basel). 12:13902021. View Article : Google Scholar

Morati F and Modesti M: Insights into the control of RAD51 nucleoprotein filament dynamics from single-molecule studies. Curr Opin Genet Dev. 71:182–187. 2021. View Article : Google Scholar : PubMed/NCBI

Wang SSY, Jie YE, Cheng SW, Ling GL and Ming HVY: PARP inhibitors in breast and ovarian cancer. Cancers (Basel). 15:23572023. View Article : Google Scholar : PubMed/NCBI

Konecny GE and Kristeleit RS: PARP inhibitors for BRCA1/2-mutated and sporadic ovarian cancer: Current practice and future directions. Br J Cancer. 115:1157–1173. 2016. View Article : Google Scholar : PubMed/NCBI

Dilmac S and Ozpolat B: Mechanisms of PARP-inhibitor-resistance in BRCA-mutated breast cancer and new therapeutic approaches. Cancers (Basel). 15:36422023. View Article : Google Scholar : PubMed/NCBI

Ghandali M, Huntington K, Srinivasan P, Dizon DS, Graff SL, Carneiro BA and El-Deiry WS: Abstract 1066: PARP inhibitor rucaparib in combination with imipridones ONC201 or ONC212 demonstrates preclinical synergy against BRCA1/2-deficient breast, ovarian and prostate cancer cells. Cancer Res. 83(7_Suppl): S10662023. View Article : Google Scholar

Vidula N, Damodaran S, Bhave M, Rugo H, Shah AN, Blouch E, Ruffle-Deignan NR, Ogbenna O, Flaum LE, Cristofanilli M, et al: Abstract PO4-19-06: Phase II study of a PARP inhibitor, talazoparib, in HER2-metastatic breast cancer with a somatic BRCA1/2 mutation present in cell-free DNA or tumor tissue genotyping. Cancer Res. 84(9_Suppl): PO4-19-062024. View Article : Google Scholar

Vidula N, Blouch E, Basile E, Ruffle-Deignan NR, Horick N, Damodaran S, Aspitia AM, Bhave M, Shah A, Liu MC, et al: Abstract OT2-24-03: Phase II study of a PARP inhibitor in metastatic breast cancer with somatic BRCA1/2 mutations identified by cell-free DNA: Genotyping based clinical trial. Cancer Res. 82(4_Suppl): OT2-24-032024. View Article : Google Scholar

Baldock RA, Pressimone CA, Baird JM, Khodakov A, Luong TT, Grundy MK, Smith CM, Karpenshif Y, Bratton-Palmer DS, Prakash R, et al: RAD51D splice variants and cancer-associated mutations reveal XRCC2 interaction to be critical for homologous recombination. DNA Repair (Amst). 76:99–107. 2019. View Article : Google Scholar : PubMed/NCBI

Castroviejo-Bermejo M, Cruz C, Llop-Guevara A, Gutiérrez-Enríquez S, Ducy M, Ibrahim YH, Gris-Oliver A, Pellegrino B, Bruna A, Guzman M, et al: A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation. EMBO Mol Med. 10:e91722018. View Article : Google Scholar : PubMed/NCBI

Pelttari LM, Khan S, Vuorela M, Kiiski JI, Vilske S, Nevanlinna V, Ranta S, Schleutker J, Winqvist R, Kallioniemi A, et al: RAD51B in familial breast cancer. PLoS One. 11:e01537882016. View Article : Google Scholar : PubMed/NCBI

Setton J, Selenica P, Mukherjee S, Shah R, Pecorari I, McMillan B, Pei IX, Kemel Y, Ceyhan-Birsoy O, Sheehan M, et al: Germline RAD51B variants confer susceptibility to breast and ovarian cancers deficient in homologous recombination. NPJ Breast Cancer. 7:1352021. View Article : Google Scholar :

Boni J, Idani A, Roca C, Feliubadaló L, Tomiak E, Weber E, Foulkes WD, Orthwein A, El Haffaf Z, Lázaro C and Rivera B: A decade of RAD51C and RAD51D germline variants in cancer. Hum Mutat. 43:285–298. 2021. View Article : Google Scholar : PubMed/NCBI

Kolinjivadi AM, Chong ST, Choudhary R, Sankar H, Chew EL, Yeo C, Chan SH and Ngeow J: Functional analysis of germline RAD51C missense variants highlight the role of RAD51C in replication fork protection. Hum Mol Genet. 32:1401–1409. 2023. View Article : Google Scholar

Yang X, Song H, Leslie G, Engel C, Hahnen E, Auber B, Horváth J, Kast K, Niederacher D, Turnbull C, et al: Ovarian and breast cancer risks associated with pathogenic variants in RAD51C and RAD51D. J Natl Cancer Inst. 112:1242–1250. 2020. View Article : Google Scholar : PubMed/NCBI

Suszyńska M, Ratajska M and Kozlowski P: BRIP1, RAD51C and RAD51D mutations are associated with high susceptibility to ovarian cancer: Mutation prevalence and precise risk estimates based on a pooled analysis of ~30,000 cases. J Ovarian Res. 13:502020. View Article : Google Scholar

Wesoła M and Jeleń M: The risk of breast cancer due to PALB2 gene mutations. Adv Clin Exp Med. 26:339–342. 2017. View Article : Google Scholar

Ruberu TLM, Braun D, Parmigiani G and Biswas S: Meta-analysis of breast cancer risk for individuals with PALB2 pathogenic variants. Genet Epidemiol. 48:448–454. 2024. View Article : Google Scholar : PubMed/NCBI

Sato K, Koyasu M, Nomura S, Sato Y, Kita M, Ashihara Y, Adachi Y, Ohno S, Iwase T, Kitagawa D, et al: Mutation status of RAD 51C, PALB 2 and BRIP 1 in 100 Japanese familial breast cancer cases without BRCA 1 and BRCA 2 mutations. Cancer Sci. 108:2287–2294. 2017. View Article : Google Scholar : PubMed/NCBI

Feng Y, Wang D, Xiong L, Zhen G and Tan J: Predictive value of RAD51 on the survival and drug responsiveness of ovarian cancer. Cancer Cell Int. 21:2492021. View Article : Google Scholar

Alizzi Z, Saravi S, Khalique S, McDonald T, Karteris E and Hall M: Identification of RAD51 foci in cancer-associated circulating cells of patients with high-grade serous ovarian cancer: Association with treatment outcomes. Int J Gynecol Cancer. 33:1427–1433. 2023. View Article : Google Scholar :

Compadre AJ, Van Biljon L, Valentine MC, Llop-Guevara A, Graham E, Fashemi B, Herencia-Ropero A, Kotnik EN, Cooper I, Harrington SP, et al: RAD51 Foci as a biomarker predictive of platinum chemotherapy response in ovarian cancer. Clin Cancer Res. 29:2466–2479. 2023. View Article : Google Scholar : PubMed/NCBI

Goel N, Foxall ME, Scalise CB, Wall JA and Arend RC: Strategies in overcoming homologous recombination proficiency and PARP inhibitor resistance. Mol Cancer Ther. 20:1542–1549. 2021. View Article : Google Scholar

McMullen M, Karakasis K, Madariaga A and Oza AM: Overcoming platinum and PARP-inhibitor resistance in ovarian cancer. Cancers (Basel). 12:16072020. View Article : Google Scholar : PubMed/NCBI

Song H, Dicks E, Ramus SJ, Tyrer JP, Intermaggio MP, Hayward J, Edlund CK, Conti D, Harrington P, Fraser L, et al: Contribution of germline mutations in the RAD51B, RAD51C and RAD51D genes to ovarian cancer in the population. J Clin Oncol. 33:2901–2907. 2015. View Article : Google Scholar :

Nguyen L, WM Martens J, Van Hoeck A and Cuppen E: Pan-cancer landscape of homologous recombination deficiency. Nat Commun. 11:55842020. View Article : Google Scholar :

Nickols NG, Maxwell KN, Lee KM, Hausler R, Anglin-Foote T, Garraway I and Lynch JA: Frequencies of actionable alterations found by somatic tumor sequencing in veterans with metastatic prostate cancer. J Clin Oncol. 40(6_suppl): S1782022. View Article : Google Scholar

Rajput M, Singh R, Singh N and Singh RP: EGFR-mediated RAD51 expression potentiates intrinsic resistance in prostate cancer via EMT and DNA repair pathways. Life Sci. 286:1200312021. View Article : Google Scholar

Maranto C, Udhane V, Hoang DT, Gu L, Alexeev V, Malas K, Cardenas K, Brody JR, Rodeck U, Bergom C, et al: STAT5A/B blockade sensitizes prostate cancer to radiation through inhibition of RAD51 and DNA repair. Clin Cancer Res. 24:1917–1931. 2018. View Article : Google Scholar : PubMed/NCBI

Arce-Gallego S, Llop-Guevara A, Carreira S, Porta N, Fasani R, Bianchini D, Seed G, Rescigno P, Paschalis A, Bertan C, et al: Abstract CT161: A homologous recombination repair (HRR) functional assay to stratify patients with metastatic prostate cancer for PARP inhibitor treatment in the TOPARP-B clinical trial. Cancer Res. 81(Suppl 13): CT1612021. View Article : Google Scholar

Mason JM, Logan HL, Budke B, Wu M, Pawłowski M, Weichselbaum RR, Kozikowski AP, Bishop DK and Connell PP: The RAD51-stimulatory compound RS-1 can exploit the RAD51 overexpression that exists in cancer cells and tumors. Cancer Res. 74:3546–3555. 2014. View Article : Google Scholar : PubMed/NCBI

Zhang Y, Park JY, Zhang F, Olson SH, Orlow I, Li Y, Kurtz RC, Ladanyi M, Chen J, Toland AE, et al: The p. Ser64Leu and p.Pro104Leu missense variants of PALB2 identified in familial pancreatic cancer patients compromise the DNA damage response. Hum Mutat. 42:150–163. 2021. View Article : Google Scholar

Nagathihalli NS and Nagaraju G: RAD51 as a potential biomarker and therapeutic target for pancreatic cancer. Biochim Biophys Acta. 1816:209–218. 2011.

Zhang X, Ma N, Yao W, Li S and Ren Z: RAD51 is a potential marker for prognosis and regulates proliferation in pancreatic cancer. Cancer Cell Int. 19:3562019. View Article : Google Scholar

COSMIC (Catalogue Of Somatic Mutations In Cancer). Sanger Institute. https://cancer.sanger.ac.uk/cosmic/gene/analysis. Note: Access to the specific data referenced requires logging into the COSMIC database. Credentials can be provided upon reasonable request to the corresponding author.

Yang X, Leslie G, Doroszuk A, Schneider S, Allen J, Decker B, Dunning AM, Redman J, Scarth J, Plaskocinska I, et al: Cancer risks associated with germline PALB2 pathogenic variants: an international study of 524 families. J Clin Oncol. 38:674–685. 2020. View Article : Google Scholar

Tischkowitz M, Balmaña J, Foulkes WD, James P, Ngeow J, Schmutzler R, Voian N, Wick MJ, Stewart DR and Pal T; ACMG Professional Practice and Guidelines Committee: Management of individuals with germline variants in PALB2: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 23:1416–1423. 2021. View Article : Google Scholar : PubMed/NCBI

Kwong A, Ho CYS, Au CH, Tey SK and Ma ESK: Germline RAD51C and RAD51D mutations in high-risk Chinese breast and/ or ovarian cancer patients and families. J Pers Med. 14:8662024. View Article : Google Scholar

Lee A, Mavaddat N, Wilcox AN, Cunningham AP, Carver T, Hartley S, Babb de Villiers C, Izquierdo A, Simard J, Schmidt MK, et al: BOADICEA: A comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors. Genet Med. 21:1708–1718. 2019. View Article : Google Scholar : PubMed/NCBI

Natiaonal Cancer Institute: Genetic: Testing for Inherited Cancer Risk. https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet. Accessed April 18, 2024

Faucett WA, Peay H and Coghlin CR II: Genetic testing: Consent and result disclosure for the primary care provider. Med Clin North Am. 103:967–976. 2019. View Article : Google Scholar :

Al-Shamsi HO, Alwbari A, Azribi F, Calaud F, Thuruthel S, Tirmazy SHH, Kullab S, Ostomane S and Abulkhair O: BRCA testing and management of BRCA-mutated early-stage breast cancer: A comprehensive statement by expert group from GCC region. Front Oncol. 14:13589822024. View Article : Google Scholar : PubMed/NCBI

Natiaonal Cancer Institute: Surgery to Reduce the Risk of Breast Cancer. https://www.cancer.gov/types/breast/risk-reducing-surgery-fact-sheet#:~:text=Risk%2Dreducing%20salpingo%2Doophorectomy%20greatly,gene%20(23%E2%80%9325). Accessed June 26, 2024

Mai PL, Miller A, Gail MH, Skates S, Lu K, Sherman ME, Ioffe OB, Rodriguez G, Cohn DE, Boggess J, et al: Risk-reducing salpingo-oophorectomy and breast cancer risk reduction in the Gynecologic Oncology Group Protocol-0199 (GOG-0199). JNCI Cancer Spectr. 4:pkz0752019. View Article : Google Scholar

Wang Y, Song Z, Zhang S, Wang X and Li P: Risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1 or BRCA2 mutation carriers: A systematic review and meta-analysis. Eur J Surg Oncol. 48:1209–1216. 2022. View Article : Google Scholar

Oceguera-Basurto P, Topete A, Oceguera-Villanueva A, Rivas-Carrillo J, Paz-Davalos M, Quintero-Ramos A and Daneri-Navarro A: Selective estrogen receptor modulators in the prevention of breast cancer in premenopausal women: A review. Transl Cancer Res. 9:4444–4456. 2020. View Article : Google Scholar : PubMed/NCBI

Peters A and Tadi P: Aromatase inhibitors. StatPearls [Internet]. StatPearls Publishing; Treasure Island, FL: 2023

American Cancer Society (ACS): Aromatase Inhibitors for Lowering Breast Cancer Risk. ACS; Atlanta, GA: 2021, https://www.cancer.org/cancer/types/breast-cancer/risk-and-preven-tion/aromatase-inhibitors-for-lowering-breast-cancer-risk.html.

Lord CJ and Ashworth A: PARP inhibitors: Synthetic lethality in the clinic. Science. 355:1152–1158. 2017. View Article : Google Scholar

Galland L, Ballot E, Mananet H, Boidot R, Lecuelle J, Albuisson J, Arnould L, Desmoulins I, Mayeur D, Kaderbhai C, et al: Efficacy of platinum-based chemotherapy in metastatic breast cancer and HRD biomarkers: Utility of exome sequencing. NPJ Breast Cancer. 8:282022. View Article : Google Scholar : PubMed/NCBI

Qiu Z, Oleinick NL and Zhang J: ATR/CHK1 inhibitors and cancer therapy. Radiother Oncol. 126:450–464. 2018. View Article : Google Scholar

Biegała Ł, Gajek A, Szymczak-Pajor I, Marczak A, Śliwińska A and Rogalska A: Targeted inhibition of the ATR/CHK1 pathway overcomes resistance to olaparib and dysregulates DNA damage response protein expression in BRCA2 MUT ovarian cancer cells. Sci Rep. 13:226592023. View Article : Google Scholar

Ha DH, Min A, Kim S, Jang H, Kim SH, Kim HJ, Ryu HS, Ku JL, Lee KH and Im SA: Antitumor effect of a WEE1 inhibitor and potentiation of olaparib sensitivity by DNA damage response modulation in triple-negative breast cancer. Sci Rep. 10:99302020. View Article : Google Scholar :

Jiang X, Bai H, Li X, Li W and Zhang Z: Current status and future prospects of PARP inhibitor clinical trials in ovarian cancer. Cancer Manag Res. 11:4371–4390. 2019. View Article : Google Scholar : PubMed/NCBI

Liposits G, Loh KP, Soto-Perez-de-Celis E, Dumas L, Battisti NML, Kadambi S, Baldini C, Banerjee S and Lichtman SM: PARP inhibitors in older patients with ovarian and breast cancer: Young International Society of Geriatric Oncology review paper. J Geriatr Oncol. 10:337–345. 2019. View Article : Google Scholar

Boussios S, Moschetta M, Karihtala P, Samartzis EP, Sheriff M, Pappas-Gogos G, Ozturk MA, Uccello M, Karathanasi A, Tringos M, et al: Development of new poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer: Quo Vadis? Ann Transl Med. 8:17062020. View Article : Google Scholar

Boussios S, Karihtala P, Moschetta M, Karathanasi A, Rassy E, Sadauskaite A and Pavlidis N: Combined strategies with poly (ADP-Ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer: A literature review. Diagnostics (Basel). 9:872019. View Article : Google Scholar : PubMed/NCBI

Plummer R: Poly(ADP-ribose) polymerase inhibition: A new direction for BRCA and triple-negative breast cancer? Breast Cancer Res. 13:2182011. View Article : Google Scholar : PubMed/NCBI

Boussios S, Abson C, Moschetta M, Rassy E, Karathanasi A, Bhat T, Ghumman F, Sheriff M and Pavlidis N: Poly (ADP-Ribose) polymerase inhibitors: Talazoparib in ovarian cancer and beyond. Drugs R D. 20:55–73. 2020. View Article : Google Scholar : PubMed/NCBI

O'Sullivan Coyne G, Chen A and Kummar S: Delivering on the promise: Poly ADP ribose polymerase inhibition as targeted anticancer therapy. Curr Opin Oncol. 27:475–481. 2015. View Article : Google Scholar

Mittica G, Ghisoni E, Giannone G, Genta S, Aglietta M, Sapino A and Valabrega G: PARP inhibitors in ovarian cancer. Recent Pat Anticancer Drug Discov. 13:392–410. 2018. View Article : Google Scholar : PubMed/NCBI

Zimmer AS, Gillard M, Lipkowitz S and Lee JM: Update on PARP inhibitors in breast cancer. Curr Treat Options Oncol. 19:212018. View Article : Google Scholar

Alva AS, Mangat PK, Garrett-Mayer E, Halabi S, Hansra D, Calfa CJ, Khalil MF, Ahn ER, Cannon TL, Crilley P, et al: Pembrolizumab in patients with metastatic breast cancer with high tumor mutational burden: Results from the targeted agent and profiling utilization registry (TAPUR) study. J Clin Oncol. 39:2443–2451. 2021. View Article : Google Scholar : PubMed/NCBI

Cortesi L, Rugo HS and Jackisch C: An Overview of PARP inhibitors for the treatment of breast cancer. Target Oncol. 16:255–282. 2021. View Article : Google Scholar

Jenner ZB, Sood AK and Coleman RL: Evaluation of rucaparib and companion diagnostics in the PARP inhibitor landscape for recurrent ovarian cancer therapy. Future Oncol. 12:1439–1456. 2016. View Article : Google Scholar

Slootbeek PHJ, Overbeek JK, Ligtenberg MJL, Van Erp NP and Mehra N: PARPing up the right tree; an overview of PARP inhibitors for metastatic castration-resistant prostate cancer. Cancer Lett. 577:2163672023. View Article : Google Scholar : PubMed/NCBI

Cruz C, Castroviejo-Bermejo M, Gutiérrez-Enríquez S, Llop-Guevara A, Ibrahim YH, Gris-Oliver A, Bonache S, Morancho B, Bruna A, Rueda OM, et al: RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer. Ann Oncol. 29:1203–1210. 2018. View Article : Google Scholar

Orhan E, Velázquez C, Tabet I, Sardet C and Theillet C: Regulation of RAD51 at the transcriptional and functional levels: What prospects for cancer therapy? Cancers (Basel). 13:29302021. View Article : Google Scholar : PubMed/NCBI

Zhao L, Si CS, Yu Y, Lu JW and Zhuang Y: Depletion of DNA damage binding protein 2 sensitizes triple-negative breast cancer cells to poly ADP-ribose polymerase inhibition by destabilizing RAD51. Cancer Sci. 110:3543–3552. 2019. View Article : Google Scholar : PubMed/NCBI

Jia Y, Song Y, Dong G, Hao C, Zhao W, Li S and Tong Z: Aberrant regulation of RAD51 promotes resistance of neoadjuvant endocrine therapy in ER-positive breast cancer. Sci Rep. 9:129392019. View Article : Google Scholar : PubMed/NCBI

Goričar K, Dugar F, Dolžan V and Marinko T: NBN, RAD51 and XRCC3 polymorphisms as potential predictive biomarkers of adjuvant radiotherapy toxicity in early HER2-positive breast cancer. Cancers (Basel). 14:43652022. View Article : Google Scholar

Yu J and Wang CG: Relationship between polymorphisms in homologous recombination repair genes RAD51 G172T, XRCC2 & XRCC3 and risk of breast cancer: A meta-analysis. Front Oncol. 13:10473362023. View Article : Google Scholar

Day M, Lapierre J, O'Shea T and Mills K: Abstract C14: A novel RAD51 inhibitor, CYT-0851, shows anticancer activity in preclinical models of pancreatic cancer. Cancer Res. 79(24_Suppl): C142019. View Article : Google Scholar

Tsai YF, Chan LP, Chen YK, Su CW, Hsu CW, Wang YY and Yuan SF: RAD51 is a poor prognostic marker and a potential therapeutic target for oral squamous cell carcinoma. Cancer Cell Int. 23:2312023. View Article : Google Scholar : PubMed/NCBI

Korsholm LM, Kjeldsen M, Perino L, Mariani L, Nyvang GB, Kristensen E, Bagger FO, Mirza MR and Rossing M: Combining homologous recombination-deficient testing and functional RAD51 analysis enhances the prediction of poly(ADP-Ribose) polymerase inhibitor sensitivity. JCO Precis Oncol. 8:e23004832024. View Article : Google Scholar :

QI AGEN: Browse the manual. Calculate HRD Score (beta). https://resources.qiagenbioinformatics.com/manuals/biomedicalgenomicsanalysis/current/index.php?manual=Calculate_HRD_Score_beta.html.

van Wijk LM, Nilas AB, Vrieling H and Vreeswijk MPG: RAD51 as a functional biomarker for homologous recombination deficiency in cancer: A promising addition to the HRD toolbox? Expert Rev Mol Diagn. 22:185–199. 2022. View Article : Google Scholar

Vogel A, Haupts A, Kloth M, Roth W and Hartmann N: A novel targeted NGS panel identifies numerous homologous recombination deficiency (HRD)-associated gene mutations in addition to known BRCA mutations. Diagn Pathol. 19:92024. View Article : Google Scholar : PubMed/NCBI

Witz A, Dardare J, Betz M, Michel C, Husson M, Gilson P, Merlin JL and Harlé A: Homologous recombination deficiency (HRD) testing landscape: Clinical applications and technical validation for routine diagnostics. Biomark Res. 13:312025. View Article : Google Scholar : PubMed/NCBI

Xu Y, Chen YA, Wu Y, Saverimuthu A, Jadhav A, Bhuiyan R, Sandler J, Yio J and Kumar V: The prognostic and predictive value of homologous recombination deficiency status in patients with advanced stage epithelial ovarian carcinoma after first-line platinum-based chemotherapy. Front Oncol. 14:13724822024. View Article : Google Scholar :

Pellegrino B, Herencia-Ropero A, Llop-Guevara A, Pedretti F, Moles-Fernández A, Viaplana C, Villacampa G, Guzmán M, Rodríguez O, Grueso J, et al: Preclinical in vivo validation of the RAD51 test for identification of homologous recombination-deficient tumors and patient stratification. Cancer Res. 82:16462022. View Article : Google Scholar

Guffanti F, Mengoli I and Damia G: Current HRD assays in ovarian cancer: Differences, pitfalls, limitations and novel approaches. Front Oncol. 14:14053612024. View Article : Google Scholar

Zhou J, Wang H, Fu F, Li Z, Feng Q, Wu W, Liu Y, Wang C and Chen Y: Spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer: Screening of 16,501 unselected patients with breast cancer and 5890 controls by next-generation sequencing. Cancer. 126:3202–3208. 2020. View Article : Google Scholar

Woods NT, Baskin R, Golubeva V, Jhuraney A, De-Gregoriis G, Vaclova T, Goldgar DE, Couch FJ, Carvalho MA, Iversen ES and Monteiro AN: Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. NPJ Genom Med. 1:160012016. View Article : Google Scholar : PubMed/NCBI

Rein HL and Bernstein KA: Finding significance: New perspectives in variant classification of the RAD51 regulators, BRCA2 and beyond. DNA Repair (Amst). 130:1035632023. View Article : Google Scholar : PubMed/NCBI

Zielli T, Labidi-Galy I, Del Grande M, Sessa C and Colombo I: The clinical challenges of homologous recombination proficiency in ovarian cancer: From intrinsic resistance to new treatment opportunities. Cancer Drug Resist. 6:499–516. 2023. View Article : Google Scholar :

Li A, Geyer FC, Blecua P, Lee JY, Selenica P, Brown DN, Pareja F, Lee SSK, Kumar R, Rivera B, et al: Homologous recombination DNA repair defects in PALB2-associated breast cancers. NPJ Breast Cancer. 5:232019. View Article : Google Scholar :