Prevalence of Homologous Recombination Deficiency in First-Line PARP Inhibitor Maintenance Clinical Trials and Further Implication of Personalized Treatment in Ovarian Cancer DOI Open Access
E Sun Paik, Ha Kyun Chang, Sang‐Hoon Lee

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(12), P. 3095 - 3095

Published: June 7, 2023

Among ovarian cancer patients with BRCA mutation or homologous recombination deficiency (HRD), the efficacy of Poly-ADP-ribose polymerase (PARP) inhibitors such as olaparib, niraparib, veliparib, and rucaparib has been proven in a number clinical trials. HRD are currently indicated for PARP inhibitor maintenance treatment cancer. diagnostic tests examine various components, resulting different status definitions and, result, decisions. A exist, but test results provided by companies may differ they use methods cutoffs. prevalence difference was shown between It is important to select an appropriate method that can present accurate phenotypes predict sensitivity so who most likely benefit from selected. Additionally, subset data trials, there race higher Japanese Chinese shown. Further large-scale investigations on racial differences needed this contribute changes determining plan personalized patients.

Language: Английский

Efficacy of Poly(ADP-ribose) Polymerase Inhibitors by Individual Genes in Homologous Recombination Repair Gene-Mutated Metastatic Castration-Resistant Prostate Cancer: A US Food and Drug Administration Pooled Analysis DOI
Jaleh Fallah, Jianjin Xu, Chana Weinstock

et al.

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(14), P. 1687 - 1698

Published: March 14, 2024

We performed a pooled analysis of multiple trials poly(ADP-ribose) polymerase inhibitors (PARPi) in metastatic castration-resistant prostate cancer (mCRPC) to investigate the efficacy PARPi each individual homologous recombination repair (HRR) mutated (m) gene.

Language: Английский

Citations

35
PARP Inhibitors in Breast Cancer: a Short Communication DOI Creative Commons
Gordon R. Daly, Maen Monketh Alrawashdeh, Jason McGrath

et al.

Current Oncology Reports, Journal Year: 2024, Volume and Issue: 26(2), P. 103 - 113

Published: Jan. 2, 2024

In the last decade, poly (ADP-ribose) polymerase (PARP) inhibitors have been approved in treatment of several cancers, such as breast and ovarian cancer. This article aims to discuss current uses, limitations, future directions for PARP (PARPis) Following results OlympiAD EMBRACA trials, PARPis were HER2-negative cancer with a germline BRCA mutation. We reviewed this class drugs' mechanism action, efficacy, well further studies that discussed resistance, impaired homologous recombination repair (HRR), combination other drugs. Improving understanding HRR, increasing ability target combining novel agents are continuing increase clinical utility PARPis.

Language: Английский

Citations

10
Double‐strand DNA break repair: molecular mechanisms and therapeutic targets DOI Creative Commons

Jinpeng Tan,

Xingyao Sun,

Hongling Zhao

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(5)

Published: Oct. 1, 2023

Abstract Double‐strand break (DSB), a significant DNA damage brought on by ionizing radiation, acts as an initiating signal in tumor radiotherapy, causing cancer cells death. The two primary pathways for DSB repair mammalian are nonhomologous end joining (NHEJ) and homologous recombination (HR), which cooperate compete with one another to achieve effective repair. mechanism depends numerous regulatory variables. recognition the recruitment of components, instance, depend MRE11–RAD50–NBS1 (MRN) complex Ku70/80 heterodimer/DNA–PKcs (DNA–PK) complex, whose control is crucial determining pathway choice efficiency HR NHEJ. In‐depth elucidation pathway's molecular mechanisms has greatly facilitated creation proteins or pathways‐specific inhibitors advance precise therapy boost effectiveness radiotherapy. architectures, roles, processes, target reviewed this article. strategy application also discussed based advancement targeted response proteins.

Language: Английский

Citations

21
Homologous Recombination Deficiency in Ovarian Cancer: from the Biological Rationale to Current Diagnostic Approaches DOI Open Access
Alessandro Mangogna, Giada Munari, Francesco Pepe

et al.

Journal of Personalized Medicine, Journal Year: 2023, Volume and Issue: 13(2), P. 284 - 284

Published: Feb. 2, 2023

The inability to efficiently repair DNA double-strand breaks using the homologous recombination pathway is defined as deficiency (HRD). This molecular phenotype represents a positive predictive biomarker for clinical use of poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors and platinum-based chemotherapy in ovarian cancers. However, HRD complex genomic signature, different methods analysis have been developed introduce testing setting. review describes technical aspects challenges related cancer outlines potential pitfalls that can be encountered diagnostics.

Language: Английский

Citations

20
Advances in PARP Inhibitors for Prostate Cancer DOI Open Access
Steven Tisseverasinghe,

Boris Bahoric,

Maurice Anidjar

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(6), P. 1849 - 1849

Published: March 20, 2023

Poly-adenosine diphosphate-ribose polymerase plays an essential role in cell function by regulating apoptosis, genomic stability and DNA repair. PARPi is a promising drug class that has gained significant traction the last decade with good outcomes different cancers. Several trials have sought to test its effectiveness metastatic castration resistant prostate cancer (mCRPC). We conducted comprehensive literature review evaluate current of this setting. To effect, we queries PubMed, Embase Cochrane databases. reviewed compared all major contemporary publications on topic. In particular, recent phase II III studies also demonstrated benefits olaparib, rucaparib, niraparib, talazoparib CRPC. Drug been assessed through radiological progression or overall response. Given notion synthetic lethality potential synergy other oncological therapies, several are looking integrate combined therapies. There remains ongoing controversy need for genetic screening prior treatment initiation as well optimal patient population, which would benefit most from PARPi. important asset arsenal mCRPC. New combinations may improve earlier phases cancer.

Language: Английский

Citations

18
Incorporating Structured and Unstructured Data Sources to Identify and Characterize Hereditary Cancer Testing Among Veterans With Metastatic Castration-Resistant Prostate Cancer DOI Creative Commons
Danielle Candelieri-Surette, Anna Hung,

Fatai Y. Agiri

et al.

JCO Clinical Cancer Informatics, Journal Year: 2025, Volume and Issue: 9

Published: Feb. 1, 2025

PURPOSE This study introduces an integrated approach using structured and unstructured data from electronic health record to identify characterize patient utilization of hereditary cancer genetic testing among patients with metastatic castration-resistant prostate (mCRPC). Secondary objectives were describe factors associated the receipt testing. METHODS retrospective cohort included a Veterans diagnosed mCRPC January 2016 December 2021. Receipt was identified data. Time testing, age at rate analyzed. Sociodemographic clinical including race, marital status, rurality, Charlson comorbidity index (CCI), counseling. RESULTS Among 9,703 who did not decline 16% received nearly half tests occurring in 2020-2021. Factors positively counseling (adjusted odds ratio [aOR], 11.07 [95% CI, 3.66 33.51]), enrollment trial (aOR, 7.42 5.59 9.84]), treatment Prostate Cancer Foundation-Veterans Affairs Center Excellence 1.43 1.04 1.95]). Negative associations older 0.95 0.93 0.97]) severe CCI score 0.82 0.71 0.94]). Trends revealed that time decreased per diagnosis year while median increased year. CONCLUSION Although rates are still suboptimal, they have steadily since 2016. Educating about benefits may further improve rates.

Language: Английский

Citations

0
Clinically relevant fusion oncogenes: detection and practical implications DOI
Maxim Sorokin,

Elizaveta Rabushko,

Julian M. Rozenberg

et al.

Therapeutic Advances in Medical Oncology, Journal Year: 2022, Volume and Issue: 14

Published: Jan. 1, 2022

Mechanistically, chimeric genes result from DNA rearrangements and include parts of preexisting normal combined at the genomic junction site. Some rearranged encode pathological proteins with altered molecular functions. Those which can aberrantly promote carcinogenesis are called fusion oncogenes. Their formation is not a rare event in human cancers, many them were documented numerous study reports specific databases. They may have various peculiarities like increased stability an oncogenic part, self-activation tyrosine kinase receptor moiety, transcriptional regulation activities. Currently, tens low mass inhibitors approved cancers as drugs targeting (RTK) proteins, that is, including ALK, ABL, EGFR, FGFR1-3, NTRK1-3, MET, RET, ROS1 moieties. Therein, presence respective RTK cancer genome diagnostic biomarker for drug prescription. However, identification such oncogenes challenging breakpoint arise multiple sites within gene, exact partner generally unknown. There no gold standard method detection, alternative experimental techniques employed nowadays to solve this issue. Among them, RNA-seq-based methods offer advantage unbiased high-throughput analysis only transcribed genes, simultaneous finding both partners single RNA-seq read. Here we focus on current knowledge biology clinical aspects related databases, laboratory detection methods.

Language: Английский

Citations

21
Morphologic Correlations With Homologous Recombination Deficiency in High-grade Serous Carcinomas DOI
Udita Chapagain,

Julia B. Huecker,

Lulu Sun

et al.

International Journal of Gynecological Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

High-grade serous carcinomas (HGSCs) with homologous recombination deficiency (HRD) respond favorably to platinum therapy and poly ADP ribose polymerase (PARP) inhibitors. Mutations in BRCA1 BRCA2 commonly cause HRD have been associated Solid, pseudoEndometrioid, Transitional-like (SET-like) histology. other repair (HRR) genes as well epigenetic changes can also result HRD; however, morphologic correlates not well-explored these cases. We hypothesized that HGSCs HRD, regardless of the etiology, are specific features. Forty-three cases HGSC genomic profiling, which included HRR gene mutation analysis score, were evaluated. The patterns, degree nuclear atypia, necrosis, mitotic index, tumor-infiltrating lymphocytes (TILs) determined. results showed HRD-high status was significantly presence BRCA1/2 mutation, SET-like morphology, geographic severe atypia. Additional pathway oncogenic mutations identified ATM, BRIP1, BLM, FANCC, CDK12, CHEK2, RAD51C , RAD51D . Almost one-third tumors did any identified. In conclusion, BRCA1/2- status, morphology more Identifying reporting patterns tumor prompt profiling prognostic, therapeutic, genetic counseling implications.

Language: Английский

Citations

0
Harnessing Pseudogenes for Lung Cancer: A Novel Epigenetic Target in Diagnosis, Prognosis and Treatment DOI
Yock Young Dan, Xinyi Zhao, Jing Li

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: 208, P. 104645 - 104645

Published: Feb. 1, 2025

Language: Английский

Citations

0
AVALIAÇÃO DA FISIOPATOLOGIA DOS EFEITOS COLATERAIS CRÔNICOS DA RADIOTERAPIA E POSSÍVEL CORRELAÇÃO GENÉTICA DE GENES DE REPARO DE FITA DUPLA DE DNA POR RECOMBINAÇÃO HOMÓLOGA DOI Open Access

Bruno Antônio Cruz Nogueira,

M Batista,

Pedro Ricardo Mendes Llobet

et al.

Revista Foco, Journal Year: 2025, Volume and Issue: 18(2), P. e7623 - e7623

Published: Feb. 3, 2025

Introdução: A radioterapia (RT) é essencial no tratamento do câncer, mas sua eficácia limitada pelos efeitos colaterais nos tecidos saudáveis, como proctite, dermatite, cistite e enterite actínicas. Esses estão associados a processos inflamatórios, fibrose, alterações vasculares depleção celular. Dessas complicações, apenas uma parcela dos pacientes as desenvolve, devido possíveis fatores genéticos relacionados à radiossensibilidade. Objetivo: Avaliar fisiopatologia crônicos da explorar possível associação entre radiossensibilidade variantes genéticas genes HR. Método: Foram localizados 544 artigos, avaliados quanto ao tema abordado 3 foram selecionados na avaliação final para compor o atual estudo. Resultados: Os estudos destacaram gene ATM principal foco, com associações patogênicas maior Um estudo mostrou altos níveis de quebras DNA não reparadas em clinicamente radiossensíveis. Outro identificou RAD51C associadas dermatite actínica. Conclusão: O perfil genético normais se mostra multifatorial poligênico. Ademais, existe predominância avaliando radiorresistência tumoral há um foco muito menor realizados normais, que exige mais nessa área permitir individualização parâmetros RT.

Citations

0