SN-38 Sensitizes BRCA-Proficient Ovarian Cancers to PARP Inhibitors through Inhibiting Homologous Recombination Repair

Lin, Shengbin; Tian, Jiaxin; He, Qiang; Yang, Minyi; Chen, Zuyang; Belogurov, A. A.; Li, Xiao; Zhang, Fan; Liu, Yongzhu; Guo, Chen

doi:10.1155/2022/7243146

Cited by 3 publications

(2 citation statements)

References 39 publications

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“…By activating the p38/MAPK pathway and inhibiting TRIM14 signaling, piperlongumine inhibited GBM growth [ 42 ]. SN-38, a CPT analogue, inhibited homologous recombination repair in BRCA-proficient ovarian cancer cells to make them susceptible to PARP inhibitor therapy [ 43 ]. Cancer immunotherapies like checkpoint inhibitors and adoptive cell therapy could stimulate the immune system to fight cancer [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

An association between ATP7B expression and human cancer prognosis and immunotherapy: a pan-cancer perspective

Zhang,

Shi

et al. 2023

BMC Med Genomics

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Background ATP7B is a copper-transporting protein that contributes to the chemo-resistance of human cancer cells. It remains unclear what the molecular mechanisms behind ATP7B are in cancer, as well as its role in human pan-cancer studies. Methods Our study evaluated the differential expression of ATP7B in cancer and paracancerous tissues based on RNA sequencing data from the GTEx and TCGA. Kaplan–Meier and Cox proportional hazards regressions were used to estimate prognostic factors associated with ATP7B.The correlations between the expression of ATP7B and immune cell infiltration, tumor mutation burden, microsatellite instability and immune checkpoint molecules were analyzed. Co-expression networks and mutations in ATP7B were analyzed using the web tools. An analysis of ATP7B expression difference on drug sensitivity on tumor cells was performed using the CTRP, GDSC and CMap database. Results ATP7B expression differed significantly between cancerous and paracancerous tissues. The abnormal expression of ATP7B was linked to prognosis in LGG and KIRC. Infiltration of immune cells, tumor mutation burden, microsatellite instability and immunomodulators had all been linked to certain types of cancer. Cancer cells exhibited a correlation between ATP7B expression and drug sensitivity. Conclusion ATP7B might be an immunotherapeutic and prognostic biomarker based on its involvement in cancer occurrence and development.

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Section: Discussionmentioning

confidence: 99%

An association between ATP7B expression and human cancer prognosis and immunotherapy: a pan-cancer perspective

Zhang,

Shi

et al. 2023

BMC Med Genomics

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“…PARP1 is a polymerase that functions in the DNA repair response to DNA damage by conjugated ADP from NAD+ to target proteins such as p53 and histones [10]. Especially, when there are defects in DNA repair caused by mutations of BRCA1/2, the inhibition of PARP1 results in unrepairable DNA and the apoptosis of cancer cells [11]. ATM is a phosphatidylinositol 3-kinase-like kinase family member.…”

Section: Introductionmentioning

confidence: 99%

Clinical Implication of DNA Damage Response Genes in Advanced Gastric Cancer Stage IV and Recurrent Gastric Cancer Patients After Gastrectomy Treated Palliative Chemotherapy

Kim¹,

Park²,

Kim³

et al. 2023

J. Cancer

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Purpose: This study aimed to investigate the relationship between DNA damage response (DDR)-related protein expression and the clinical outcomes of patients with gastric cancer stage IV and recurrent advanced gastric cancer patients after gastrectomy treated with palliative first-line chemotherapy. Materials and Methods: A total of 611 gastric cancer patients underwent D2 radical gastrectomy at Chung-Ang University Hospital between January 2005 and December 2017, of which 72 patients who received gastrectomy treatment with palliative chemotherapy were enrolled in this study. We performed the immunohistochemical assessment of MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), at-rich interaction domain 1 (ARID1A), poly adenosine diphosphate-ribose polymerase 1 (PARP-1), breast cancer susceptibility gene 1 (BRCA1), and ataxia-telangiectasia mutated (ATM) using formalin-fixed paraffin-embedded samples. In addition, Kaplan-Meier survival analysis and Cox regression models were used to evaluate independent predictors of overall survival (OS) and progression-free survival (PFS). Results: Among the 72 patients studied, immunohistochemical staining analysis indicated deficient DNA mismatch repair (dMMR) in 19.4% of patients (n = 14). The most common DDR gene with suppressed expression was PARP-1 (n = 41, 56.9%), followed by ATM (n = 26, 36.1%), ARID1A (n = 10, 13.9%), MLH1 (n = 12, 16.7%), BRCA1 (n = 11, 15.3%), and MSH2 (n = 3, 4.2%). HER2 (n = 6, 8.3%) and PD-L1 (n = 3, 4.2%) were expressed in 72 patients. The dMMR group exhibited a significantly longer median OS than the MMR proficient (pMMR) group (19.9 months vs. 11.0 months; hazard ratio [HR] 0.474, 95% confidence interval [CI] = 0.239-0.937, P = 0.032). The dMMR group exhibited a significantly longer median PFS than the pMMR group (7.0 months vs. 5.1 months; HR= 0.498, 95% CI = 0.267-0.928, P = 0.028). Conclusions: Of stage IV gastric cancer and recurrent gastric cancer patients who underwent gastrectomy, the dMMR group had a better survival rate than the pMMR group. Although dMMR is a predictive factor for immunotherapy in advanced gastric cancer, further studies are needed to determine whether it is a prognostic factor for gastric cancer patients treated with palliative cytotoxic chemotherapy.

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Design, synthesis and development of a dual inhibitor of Topoisomerase 1 and poly (ADP-ribose) polymerase 1 for efficient killing of cancer cells

Majumdar

Shree

Das

et al. 2023

European Journal of Medicinal Chemistry

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SN-38 Sensitizes BRCA-Proficient Ovarian Cancers to PARP Inhibitors through Inhibiting Homologous Recombination Repair

Cited by 3 publications

References 39 publications

An association between ATP7B expression and human cancer prognosis and immunotherapy: a pan-cancer perspective

An association between ATP7B expression and human cancer prognosis and immunotherapy: a pan-cancer perspective

Clinical Implication of DNA Damage Response Genes in Advanced Gastric Cancer Stage IV and Recurrent Gastric Cancer Patients After Gastrectomy Treated Palliative Chemotherapy

Design, synthesis and development of a dual inhibitor of Topoisomerase 1 and poly (ADP-ribose) polymerase 1 for efficient killing of cancer cells

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