Efficacy and safety of PARP inhibitors for maintenance treatment of ovarian cancer, regardless of BRCA or HRD status: a comprehensive updated meta-analysis

Li, Yanhui

doi:10.1080/01443615.2023.2171282

Cited by 5 publications

(4 citation statements)

References 43 publications

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“…The same goes for SB590885, a preclinical selective BRAF inhibitor [73]. It has been established that PARP inhibitors could prolong the survival of OC patients with or without homologous recombination de ciency, including BRCA1/2 mutation [74,75]. However, it should be noted that our Risk score model may not be able to offer guidance for PARP inhibitors due to their unique mechanism of synthetic lethality.…”

Section: Discussionmentioning

confidence: 92%

Construction of a mitochondria genes-based model for prognosis prediction, drug guidance and immune feature analysis in ovarian serous cystadenocarcinoma

Shen

Ding

et al. 2023

Preprint

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Background Ovarian serous cystadenocarcinoma (OSC) is the most common pathological subtype of ovarian cancer (OC) associated with high mortality. Albeit dysregulated mitochondrial metabolism has been implicated with OC, the role of mitochondrial genes in OSC remains unclear. We sought to construct a model based on mitochondrial genes for prognosis prediction, drug guidance and immune feature analysis of OSC. Methods Differentially expressed genes (DEGs) and mitochondrial-related DEGs (MRGs) were identified through the Cancer Genome Atlas (TCGA)-OV dataset. Consensus clustering algorithm was applied to classify OSC patients into distinct MRGs subtypes. Prognosis-related MRGs were screened to construct the prognosis-related Risk score model, which was verified using GSE26193 dataset and immunohistochemistry (IHC) score model based on staining intensity and extent scores of MRGs. A visualized nomogram was developed to predict 1-, 3- and 5-year overall survival (OS) and drug response. The correlation of MRGs subtypes with risk subgroups and the association of Risk score model with immune response and infiltration were also investigated. Results 341 MRGs were identified from TCGA-OV, and OSC patients could be mainly divided into two MRGs subtypes. A novel prognostic Risk score model based on 7-MRGs, including ACOT13, ACSS3, COA6, HINT2, MRPL14, NDUFC2 and NDUFV2, was developed and validated via GSE26193 dataset and IHC score model. Patients in the low-risk group had a significantly longer OS. The nomogram exhibited good prognostic assessment accuracy in both training and validation datasets. Drug sensitivity analysis indicated that cisplatin, paclitaxel and docetaxel were more sensitive in the low-risk group; VEGFR inhibitor Axitinib, and BRAF inhibitors Vemurafenib and SB590885 showed better sensitivity in the high-risk group; moreover, patients in the low-risk group could have better anti-PD-1 immunotherapy response. Patients in “cluster1” MRGs subtype had lower risk scores and better immunotherapy response scores than the “cluster2” subgroup. More significant infiltrated tumor killing cells (CD8+ T cells) and higher M1 / M2 macrophage ratio were in “cluster1” patients. Conclusions Our novel 7 MRGs-based Risk score model has huge prospects to evaluate the prognosis and guide drug treatment. The favorable prognosis associated with the low-risk group is closely related to better immune response and more significant anti-tumor cellular infiltration.

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Section: Discussionmentioning

confidence: 92%

Construction of a mitochondria genes-based model for prognosis prediction, drug guidance and immune feature analysis in ovarian serous cystadenocarcinoma

Shen

Ding

et al. 2023

Preprint

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“…Literature proposes several meta-analyses which evaluate the efficacy of PARP inhibitors both as maintenance therapy after first line chemotherapy (8) as maintenance therapy in platinum-sensitive recurrence (10) confirming the recommendation for the use of PARP inhibitors in patients with ovarian cancer, albeit with different levels of benefit based on the HRD phenotype. It therefore appears evident that BRCA and HRD status substantially change the therapeutic strategies in the treatment of ovarian cancer.…”

Section: Parp Inhibitorsmentioning

confidence: 88%

“…Their use as maintenance therapy after response to platinum-based first-line chemotherapy has led to a significant prolongation of the Progression Free Survival (PFS) and of overall survival (OS), particularly in BRCA-mutated patients. In the course of the years and studies, it has emerged that this effect is not limited to BRCA mutated patients but is also extended, albeit to a respectively decreasing extent, to BRCA-wild type patients yet with other mutations of the HR, to patients who do not have defects of HR also known as Homologous recombination Proficient (HRP) as well as patients with unknown mutational status (8). Bearing in mind that ovarian cancer tends to recur in 70% of cases within 3 years of first line chemotherapy (9), it is important to underline the role of maintenance therapy in delay disease progression, prevent recurrence and prolong the disease-free interval.…”

Section: Introductionmentioning

confidence: 99%

How BRCA and homologous recombination deficiency change therapeutic strategies in ovarian cancer: a review of literature

Arcieri,

Tius,

Andreetta

et al. 2024

Front. Oncol.

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About 50% of High Grade Serous Ovarian Cancer exhibit a high degree of genomic instability due to mutation of genes involved in Homologous Recombination (HRD) and such defect accounts for synthetic lethality mechanism of PARP inhibitors (PARP-i). Several clinical trials have shown how BRCA and HRD mutational status profoundly affect first line chemotherapy as well as response to maintenance therapy with PARP-i, hence Progression Free Survival and Overall Survival. Consequently, there is urgent need for the development of increasingly reliable HRD tests, overcoming present limitations, as they play a key role in the diagnostic and therapeutic process as well as have a prognostic and predictive value. In this review we offer an overview of the state of the art regarding the actual knowledge about BRCA and HRD mutational status, the rationale of PARPi use and HRD testing (current and in development assays) and their implications in clinical practice and in the treatment decision process, in order to optimize and choose the best tailored therapy in patients with ovarian cancer.

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“…Recent years have seen the development of new therapeutics and PARP inhibitors have attracted particular attention. These drugs are being introduced into standard care and through synthetic lethality show particular activity in patients with defects in the homologous recombination DNA repair pathway [ 3 ]. Excitingly, data from the SOLO clinical trial are sufficiently mature to provide data for patients who have received olaparib for a prolonged period.…”

Section: Introductionmentioning

confidence: 99%

Ivermectin Augments the Anti-Cancer Activity of Pitavastatin in Ovarian Cancer Cells

Jawad

Richardson

2023

Diseases

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We have previously shown that pitavastatin has the potential to be used to treat ovarian cancer, although relatively high doses are likely to be necessary. One solution to this problem is to identify drugs that are synergistic with pitavastatin, thereby reducing the dose that is necessary to have a therapeutic effect. Here, we tested combinations of pitavastatin with the anti-parasitic drug ivermectin in six ovarian cancer cell lines. When tested on its own, ivermectin inhibited the growth of the cells but only with modest potency (IC50 = 10–20 µM). When the drugs were combined and assessed in cell growth assays, ivermectin showed synergy with pitavastatin in 3 cell lines and this was most evident in COV-318 cells (combination index ~ 0.6). Ivermectin potentiated the reduction in COV-318 cell viability caused by pitavastatin by 20–25% as well as potentiating apoptosis induced by pitavastatin, assessed by activation of caspase-3/7 (2–4 fold) and annexin-labelling (3–5 fold). These data suggest that ivermectin may be useful in the treatment of ovarian cancer when combined with pitavastatin, but methods to achieve an adequate ivermectin concentration in tumour tissue will be necessary.

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Efficacy and safety of PARP inhibitors for maintenance treatment of ovarian cancer, regardless of BRCA or HRD status: a comprehensive updated meta-analysis

Cited by 5 publications

References 43 publications

Construction of a mitochondria genes-based model for prognosis prediction, drug guidance and immune feature analysis in ovarian serous cystadenocarcinoma

Construction of a mitochondria genes-based model for prognosis prediction, drug guidance and immune feature analysis in ovarian serous cystadenocarcinoma

How BRCA and homologous recombination deficiency change therapeutic strategies in ovarian cancer: a review of literature

Ivermectin Augments the Anti-Cancer Activity of Pitavastatin in Ovarian Cancer Cells

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