PARP inhibitors and immunotherapy in ovarian and endometrial cancers.

Advanced ovarian and endometrial cancers have historically been associated with poor prognosis and few treatment options, limited to single or doublet chemotherapy regimens. The introduction of novel target therapies has transformed the management of these cancers. In contrast to chemotherapy, which inhibits DNA replication and mitosis, targeted therapies target cancer signalling pathways, stroma, immune-microenvironment and vasculature in tumour tissues. The most notable advances in gynaecological cancers have come from the introduction of PARP inhibitors and immune checkpoint inhibitors for ovarian and endometrial cancer, respectively. Several PARP inhibitors, which target defective DNA repair, have been approved as maintenance therapy for advanced ovarian cancer in both the first line and platinum-sensitive relapsed settings. Immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies have proven successful in advanced mismatch repair deficient endometrial cancers with use now being investigated beyond this population. This review will explore the biological rationale and clinical evidence behind the use of PARP inhibitors and immunotherapy in ovarian and endometrial cancers.

Monoamine oxidase inhibitory activity in tobacco smoke varies with tobacco type.

BACKGROUND: It has been suggested that inhibition of monoamine oxidase (MAO) activity by components of cigarette smoke may impact on smoking addiction, but it is unclear to what extent the known MAO inhibitors in tobacco smoke cause this inhibition. METHODS: MAO inhibitory activity was measured in a series of tobacco particulate matter preparations from different brands of cigarette and loose-leaf tobacco commonly available in New Zealand. RESULTS: When tobacco extracts were diluted to contain a physiologically relevant nicotine concentration of 0.2 µM, all samples tested inhibited MAO-A and MAO-B by between 4% and 12% in a standard assay. Per mg of nicotine, samples from factory-made cigarettes contained significantly less MAO inhibitory activity than did samples from loose-leaf tobacco. When inhibitory activity was calculated on a per mg of tar basis, there was no significant difference between loose-leaf tobaccos and factory-made cigarettes. CONCLUSIONS: The present study shows that the ratio of nicotine to MAO inhibitory activity varies depending on the type of tobacco product used. The roll-your-own tobaccos tested delivered more tar and more MAO inhibitory activity per mg of nicotine than the factory-made cigarettes. These findings suggest that smokers of roll-your-own tobacco may experience greater difficulty in stopping smoking.