ABSTRACT
BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) inhibitors belong to the class of drugs that inhibit the activity of the PI3K protein, which is commonly overexpressed in breast cancer cells. However, there is a need to summarize the evidence to provide conclusive advice on the benefit of PI3K inhibitors in breast cancer patients. Therefore, this review assessed the effectiveness and safety of the PI3K inhibitors amongst breast cancer patients. METHODS: Searches were made in PubMed Central, EMBASE, MEDLINE, SCOPUS, CENTRAL, WHO trial registry and Clinicaltrials.gov up to December 2022. Meta-analysis was executed using the random-effects model. Pooled hazard ratio (HR)/risk ratio (RR) was reported with 95% confidence intervals (CIs). RESULTS: In total, 13 studies were included in the analysis. Most were multi-country studies and had a higher risk of bias. Regarding the efficacy parameters, pooled HR for progression-free survival was 0.79 (95%CI: 0.67-0.92), pooled RR for complete response was 1.54 [95%CI: 1.14 to 2.09], partial response was 1.18 [95%CI: 0.87-1.61], overall response was 1.20 [95%CI: 0.93-1.56], stable disease was 1.09 [95%CI: 0.78-1.53], progressive disease was 0.80 [95%CI: 0.74 to 0.87], and clinical benefit was 1.08 [95%CI: 0.80-1.49]. For safety parameters, pooled RR for hyperglycemia was 4.57 [95%CI: 3.15-6.62], and gastrointestinal toxicity was 1.82 [95%CI: 1.56 to 2.14]. CONCLUSION: PI3K inhibitors had better efficacy than the present standard of concern for patients with breast cancer, especially among patients with PIK3CA mutations. Hence, clinicians and oncologists can provide this drug for the target population with extra caution for diabetes patients.
ABSTRACT
Objective: To investigate whether miR-193a-5p targets CDK14 and regulates the proliferation and epithelial-mesenchymal transition (EMT) of ovarian cancer cell line OVAC. Methods: TargetScanHuman was used to analyze the match between miR-193a-5p and CDK14, and then miRNA assay was used to detect whether miR-193a-5p targeting CDK14; miR-193a-5p mimics overexpression or miR-193a-5p inhibitor knockdown in the case of low miR-193a-5p, the expression levels of CDK14, EMT-related proteins E-cadherin, vimentin, fibronectin and N-cadherin were detected by immunoblotting, and the proliferation of ovarian cancer cells OVAC was detected by CCK-8, and the cell viability of cancer cell OVAC was detected by MMT. Results: miR-193a-5p targeted the 3'UTR of CDK14; after overexpression of miR-193a-5, the expression of CDK14 was decreased, the expression of EMT-related protein E-cadherin was increased, and the expressions of vimentin, fibronectin and N-cadherin were decreased. The proliferation and cell viability of ovarian cancer cell line OVAC were increased. Meanwhile, after knocking down miR-193a-5p, the expression of CDK14 was increased, and the expression of EMT-related protein E-cadherin was decreased, while the expression levels of vimentin, fibronectin and N-cadherin were increased, and the proliferation and cell viability of ovarian cancer cell line OVAC were decreased. Conclusion: miR-193a-5p reduces the proliferation, cell viability and EMT of ovarian cancer cell line OVAC by targeting the 3 'UTR of CDK14.
