Current Opinion in Pharmacology

The proton-sensing receptor ovarian cancer G-protein coupled receptor 1 (OGR1) in airway physiology and disease

Numerous G protein-coupled receptors (GPCRs) regulate multiple airway functions and play fundamental roles in normal and aberrant airway and lung physiology. Thus, GPCRs are prime candidates of targeting by disease therapeutics. The intriguing proton-sensing GPCR Ovarian cancer G-protein coupled receptor 1 (OGR1; aka GPR68) has recently been shown capable of regulating airway smooth muscle (ASM) contraction and proliferation. Although the study of OGR1 has been confounded by the fact that the proton is the presumed cognate ligand of OGR1, recent studies have begun to identify novel ligands and modulators capable of regulating the diverse signaling, and functional role of OGR1. Such studies offer hope for OGR1-targeting drugs as therapeutics for obstructive lung diseases such as asthma. Herein, we review the literature to date detailing the receptor biology and pharmacology of OGR1, receptor function in the airway, and describe the potential clinical utility of OGR1-modulating drugs.

Targeting DNA damage repair precision medicine strategies in cancer

DNA repair targeted therapeutics is a promising precision medicine strategy in cancer. The development and clinical use of PARP inhibitors has transformed lives for many patients with BRCA germline deficient breast and ovarian cancer as well as platinum sensitive epithelial ovarian cancers. However, lessons learnt from the clinical use of PARP inhibitors also confirm that not all patients respond either due to intrinsic or acquired resistance. Therefore, the search for additional synthetic lethality approaches is an active area of translational and clinical research. Here, we review the current clinical state of PARP inhibitors and other evolving DNA repair targets including ATM, ATR, WEE1 inhibitors and others in cancer.

Genomic landscape analyses in cervical carcinoma and consequences for treatment

Where we are on the road to 'tailor-made' precision medicine for drug-resistant cervical carcinoma? We explored studies about analyses of viral and human genomes, epigenomes and transcriptomes, DNA mutation analyses, their importance in detecting HPV sequences, mechanisms of drug resistance to established and targeted therapies with small molecule or therapeutic antibodies, to radiosensitivity and to chemoradiotherapy. The value of repurposing of old drugs initially approved for other disease indications and now considered for cervix cancer therapy is also discussed. The microbiome influences drug response and survival too. HPV genomic integration sites were less significant. Nomograms (Lee et al., 2013) even outperformed FIGO staging regarding prediction of five-year overall survival times. We conclude that there are still many loose threads to be followed up, before coherent conclusions for individualized therapy of drug-resistant cervical carcinoma can be drawn.