Landscape of cancer biomarker testing in England following genomic services reconfiguration: insights from a nationwide pathologist survey.

AIMS: Cancer diagnostics have been evolving rapidly. In England, the new National Health Service Genomic Medicine Service (GMS) provides centralised access to genomic testing via seven regional Genomic Laboratory Hubs. The PATHways survey aimed to capture pathologists' experience with current diagnostic pathways and opportunities for optimisation to ensure equitable and timely access to biomarker testing. METHODS: A nationwide survey was conducted with consultant pathologists from regional laboratories, via direct interviews based on a structured questionnaire. Descriptive analysis of responses was undertaken using quantitative and qualitative methods. RESULTS: Fifteen regional centres completed the survey covering a median population size of 2.5 (1.9-3.6) million (each for n=12). The median estimated turnaround time (calendar days) for standard molecular markers in melanoma, breast and lung cancers ranged from 2 to 3 days by immunohistochemistry (excluding NTRKfus in breast and lung cancers, and PD-L1 in melanoma) and 6-15 days by real-time-PCR (excluding KIT for melanoma), to 17.5-24.5 days by next-generation sequencing (excluding PIK3CA for breast cancer). Tests were mainly initiated by pathologists and oncologists. All respondents discussed the results at multidisciplinary team (MDT) meetings. The GMS roll-out was perceived to have high impact on services by 53% of respondents, citing logistical and technical issues. Enhanced education on new pathways, tissue requirements, report interpretation, providing patient information and best practice sharing was suggested for pathologists and other MDT members. CONCLUSION: Our survey highlighted the role of regional pathology within the evolving diagnostic landscape in England. Notable recommendations included improved communication and education, active stakeholder engagement, and tackling informatics barriers.

Chemosensing ensembles for monitoring biomembrane transport in real time.

The efficacy of drugs and biomolecules relies on their ability to pass through the bilayer. The development of methods to directly and sensitively monitor these membrane transport processes has remained an experimental challenge. A macrocyclic host (p-sulfonatocalix[4]arene or cucurbit[7]uril) and a fluorescent dye (lucigenin or berberine) are encapsulated as a chemosensing ensemble inside liposomes, which allows for a direct, real-time fluorescence monitoring of the passage of unlabeled bioorganic analytes. This in vitro assay is transferable to different channel proteins and analytes, has potential for fluorescence-based screening, e.g., of channel modulators, and yields the absolute kinetics of translocation. Using this new biophysical method, we observed for the first time direct rapid translocation of protamine, an antimicrobial peptide, through the bacterial transmembrane protein OmpF.