Genetic complexity and DNA damage repair defects are common in different cancer types and can induce tumor-specific vulnerabilities. Poly(ADP-ribose) polymerase (PARP) inhibitors exploit defects in the DNA repair pathway through synthetic lethality and have emerged as promising anticancer therapies, especially in tumors harboring deleterious germline or somatic breast cancer susceptibility gene (BRCA ) mutations. However, the utility of PARP inhibitors could be expanded beyond germline BRCA1/2 mutated cancers by causing DNA damage with cytotoxic agents in the presence of a DNA repair inhibitor. US Food and Drug Administration (FDA)-approved PARP inhibitors include olaparib, rucaparib, and niraparib, while veliparib is in the late stage of clinical development. Talazoparib inhibits PARP catalytic activity, trapping PARP1/2 on damaged DNA, and it has been approved by the US FDA for the treatment of metastatic germline BRCA1/2 mutated breast cancers in October 2018. The talazoparib side effect profile more closely resembles traditional chemotherapeutics rather than other clinically approved PARP inhibitors. In this review, we discuss the scientific evidence that has emerged from both experimental and clinical studies in the development of talazoparib. Future directions will include optimizing combination therapy with chemotherapy, immunotherapies and targeted therapies, and in developing and validating biomarkers for patient selection and stratification, particularly in malignancies with 'BRCAness'.
Key PointsPARP inhibitors are a family of enzymes that play a role in DNA repair.
In patients undergoing supravesical urinary diversion for benign disease in whom the bladder remains in situ the risks of complications related to the defunctionalized bladder are more than 50% and 25% of patients subsequently need cystectomy. These patients should be offered primary cystectomy at urinary diversion.
Background:
The purpose of this study was to carry an extended literature review to compare antimuscarnics with beta adrenergic agonists (mirabegron) in treatment of overactive bladder.
Materials and methods:
A literature review was carried out, using key words in different databases including MEDLINE, PUBMED, and EMBASE. All relevant published articles during last 5 years with full texts available were included in this review for critical analysis and evaluation. In total, there were 20 studies including 7 systemic reviews, 6 retrospective cohort, 3 prospective cohort, 2 randomized controlled trials, and 2 cross sectional studies.
Results:
After critical evaluation the results were considered under parameters of efficacy, adverse effects, adherence and persistence, tolerability, cost-effectiveness. In 9 studies efficacy was evaluated, 5 studies dealt with adverse effects, same number evaluated adherence and persistence. Cost effectiveness was compared in 3 and same number of studies also compared tolerability.
Conclusions:
To conclude, we found mirabegron is as efficacious as any other antimuscarnics, has better tolerability (including elderly), has better adverse effect profile, is cost effective, has better persistence and adherence rates at 12 months.
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