Rural Caregivers' Willingness for Community Pharmacists to Administer the HPV Vaccine to Their Age-Eligible Children.

Human papillomavirus (HPV) vaccination uptake varies by geographic regions with rural, often medically underserved areas, lagging behind more urban regions in terms of vaccine initiation and completion. In these regions, pharmacies may serve as an additional location for HPV vaccine administration. Little is known about rural caregivers' willingness to have their HPV vaccine age-eligible children obtain this vaccine from their local pharmacist. First and second authors conducted 26 in-depth interviews with caregivers of HPV vaccine age-eligible children living in rural regions of a southwestern state to explore their perceptions of the HPV vaccine and their willingness for pharmacist-administered HPV vaccination. They analyzed interview data using an inductive qualitative content analyses approach. The majority of caregivers were unaware that pharmacists could offer adolescent vaccines. However, most were willing to allow their children to receive the vaccine from this non-traditional source. Comments related to obtaining vaccinations from pharmacists related mostly to concerns about proper training and their certification to vaccinate against HPV. Caregivers believed that having a pharmacist administer the HPV vaccine would not affect their relationship with their primary care provider. Caregivers preferred print health education resources and were interested in also receiving health information via social media to learn more about the HPV vaccine and pharmacists' role in HPV vaccine administration. Pharmacies may serve as an additional site to increase HPV vaccine initiation and completion. Rural regions need additional health information about the HPV vaccine and pharmacists' abilities to administer this cancer prevention resource.

A novel small molecule inhibitor of the DNA repair protein Ku70/80.

Non-Homologous End-Joining (NHEJ) is the predominant pathway for the repair of DNA double strand breaks (DSBs) in human cells. The NHEJ pathway is frequently upregulated in several solid cancers as a compensatory mechanism for a separate DSB repair defect or for innate genomic instability, making this pathway a powerful target for synthetic lethality approaches. In addition, NHEJ reduces the efficacy of cancer treatment modalities which rely on the introduction of DSBs, like radiation therapy or genotoxic chemotherapy. Consequently, inhibition of the NHEJ pathway can modulate a radiation- or chemo-refractory disease presentation. The Ku70/80 heterodimer protein plays a pivotal role in the NHEJ process. It possesses a ring-shaped structure with high affinity for DSBs and serves as the first responder and central scaffold around which the rest of the repair complex is assembled. Because of this central position, the Ku70/80 dimer is a logical target for the disruption of the entire NHEJ pathway. Surprisingly, specific inhibitors of the Ku70/80 heterodimer are currently not available. We here describe an in silico, pocket-based drug discovery methodology utilizing the crystal structure of the Ku70/80 heterodimer. We identified a novel putative small molecule binding pocket and selected several potential inhibitors by computational screening. Subsequent biological screening resulted in the first identification of a compound with confirmed Ku-inhibitory activity in the low micro-molar range, capable of disrupting the binding of Ku70/80 to DNA substrates and impairing Ku-dependent activation of another NHEJ factor, the DNA-PKCS kinase. Importantly, this compound synergistically sensitized human cell lines to radiation treatment, indicating a clear potential to diminish DSB repair. The chemical scaffold we here describe can be utilized as a lead-generating platform for the design and development of a novel class of anti-cancer agents.