Exploiting <scp>DNA</scp> damage without repair: The activity of platinum chemotherapy in <scp>BRCA</scp>‐mutated prostate cancers

Humeniuk, Michael S.; Zhang, Tian; Armstrong, Andrew J.

doi:10.1002/cncr.30806

Cited by 7 publications

(3 citation statements)

References 24 publications

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“…A second wave of discoveries linked more complex genomic alterations to specific drug allocations. Examples were the use of immunotherapies in patients with high tumour mutational burden (TMB), 8 PARP inhibitors or platinum compounds in patients with genome-wide traits of DNA damage repair (DDR) impairment, 9 , 10 , 11 , 12 or those associations of a specific gain-of-function or loss-of-function event with high sensitivity to an agent that targets a pathway different to that in where the mutations lie. 13 Currently, a third wave of studies is trying to find associations between genomes lacking alterations of the former types and response to specific drugs or drug combinations.…”

Section: Introductionmentioning

confidence: 99%

Usefulness and real-world outcomes of next generation sequencing testing in patients with cancer: an observational study on the impact of selection based on clinical judgement

et al. 2023

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Section: Introductionmentioning

confidence: 99%

Usefulness and real-world outcomes of next generation sequencing testing in patients with cancer: an observational study on the impact of selection based on clinical judgement

et al. 2023

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“…Nestes pacientes, foram identificados oito com variantes no gene BRCA, sendo que seis desses oito homens (75%) com essas mutações no BRCA2 tiveram uma maior resposta do antígeno específico da próstata (PSA) ≥50% dentro de 12 semanas de terapia em comparação com homens que não possuíam essa variação. 7 Diante do exposto o presente estudo teve como objetivo realizar uma revisão bibliográfica sobre as mutações nos genes BRCA e verificar sua associação com a predisposição ao câncer de próstata bem como o prognóstico e a sobrevida dos pacientes.…”

Section: Introductionunclassified

Caracterização de variantes patogênicas nos genes BRCA 1 e 2 e suas associações com câncer de próstata

Höehr Zwetsch,

Marcon Kaspary,

Dalla Lasta Frigeri

et al. 2022

RIPS

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Objetivo: verificar em bases de dados as variantes patogênicas associadas aos genes BRCA 1 e 2 e sua associação com câncer de próstata e relacionar a ocorrência de variantes patogênicas nos genes BRCA 1 e 2 com a incidência e mau prognóstico do câncer de próstata. Método: foi realizada uma revisão bibliográfica na base de dados PubMed usando os descritores em inglês e português: mutation (mutação), BRCA, prostate cancer (câncer de próstata) cruzados aleatoriamente nos últimos 10 anos. Resultados: foram encontrados 132 artigos específicos com o as palavras, destes 11 artigos preencheram os critérios de inclusão. A partir dos dados coletados, observou-se uma associação nas variantes patogênicas do BRCA 1 e 2 com câncer de próstata (CaP). A prevalência das mutações entre BRCA1 e BRCA2 divergiu conforme os artigos, sendo mais frequentes mutações deletérias nos genes em questão. Contudo todas foram fortemente associadas ao CaP e mau prognóstico. Considerações finais: apesar de a literatura divergir entre as prevalências e tipos das mutações, devido à variações metodológicas e características da amostra, é importante a realização de pesquisas bibliográficas que avaliam o impacto das variantes patogênicas BRCA 1 e 2 no manejo do paciente com câncer de próstata, já que a presença está associada a um mau prognóstico.

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“…J Gastrointest Oncol 2018;9(6):1198-1206 jgo.amegroups.com platinum-sensitivity are seen in breast and prostate cancer (10,21,22).…”

mentioning

confidence: 99%

Low ATM expression and progression-free and overall survival in advanced gastric cancer patients treated with first-line XELOX chemotherapy

Klempner

Bhangoo

Luu

et al. 2018

J. Gastrointest. Oncol

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Background: Gastric cancer (GC) is a leading cause of cancer-specific mortality with limited biologically informed treatments. The ataxia telangiectasia mutated (ATM) gene is critically involved in the repair of double-stranded DNA breaks and a component of DNA damage repair (DDR) pathways. Platinum salts are hypothesized to have increased efficacy in tumors deficient in DDR pathways. We sought to investigate an association between ATM status and response to XELOX in a homogenous first line GC patient cohort. Methods: A clinically annotated cohort of 137 Korean patients with advanced GC treated with first-line XELOX was retrospectively examined for ATM status by immunohistochemistry. Correlation between ATM expression and clinicopathologic variables was performed by two-tailed, unpaired t-tests and Fisher's exact tests. Kaplan-Meier survival analysis curves and Cox proportional hazards models were used to evaluate for independent predictors of disease-free survival (DFS) and overall survival (OS). Results: Low ATM expression was observed in 19.0% (26/137) of patients and was not associated with clinicopathologic features or response rate to XELOX. Univariate, but not multivariable, logistic regression and Cox analysis identified ATM as an independent risk factor influencing OS and DFS. A higher ECOG score independently predicted worse survival [hazard ratio (HR) 2.96, P=0.016] and complete surgical resection independently protected against progression of disease (HR 0.69, P=0.007). Conclusions: Low ATM expression was not associated with increased response rates to XELOX in a single-institution cohort of advanced GC patients. Similarly, ATM status did not predict DFS or OS after platinum-based chemotherapy.

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Exploiting DNA damage without repair: The activity of platinum chemotherapy in BRCA‐mutated prostate cancers

Cited by 7 publications

References 24 publications

Usefulness and real-world outcomes of next generation sequencing testing in patients with cancer: an observational study on the impact of selection based on clinical judgement

Usefulness and real-world outcomes of next generation sequencing testing in patients with cancer: an observational study on the impact of selection based on clinical judgement

Caracterização de variantes patogênicas nos genes BRCA 1 e 2 e suas associações com câncer de próstata

Low ATM expression and progression-free and overall survival in advanced gastric cancer patients treated with first-line XELOX chemotherapy

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