Global Cancer Drug Development-A Report From the 2022 Accelerating Anticancer Agent Development and Validation Meeting.

Rapidly expanding systemic treatment options, combined with improved screening, diagnostic, surgical, and radiotherapy techniques, have led to improved survival outcomes for many cancers over time. However, these overall survival gains have disproportionately benefited patients in high-income countries, whereas patients in low- and middle-income countries (LMICs) continue to experience challenges in accessing timely and guideline concordant care. In September 2022, the Accelerating Anticancer Agent Development and Validation workshop was held, focusing on global cancer drug development. Panelists discussed key barriers such as the lack of diagnostic services and human resources, drug accessibility and affordability, lack of research infrastructure, and regulatory and authorization challenges, with a particular focus on Africa and Latin America. Potential opportunities to improve access and affordability were reviewed, such as the importance of prioritizing investments in diagnostics, investing health infrastructure and work force planning, coordinated drug procurement efforts and streamlined regulatory processing, incentivized pricing through regulatory change, and the importance of developing and promoting clinical trials that can answer relevant clinical questions for patients in LMICs. As a cancer community, we must continue to advocate for and work toward equitable access to high-quality interventions for patients, regardless of their geographical location.

Addressing the dichotomy between individual and societal approaches to personalised medicine in oncology.

Academic, industry, regulatory leaders and patient advocates in cancer clinical research met in November 2018 at the Innovation and Biomarkers in Cancer Drug Development meeting in Brussels to address the existing dichotomy between increasing calls for personalised oncology approaches based on individual molecular profiles and the need to make resource and regulatory decisions at the societal level in differing health-care delivery systems around the globe. Novel clinical trial designs, the utility and limitations of real-world evidence (RWE) and emerging technologies for profiling patient tumours and tumour-derived DNA in plasma were discussed. While randomised clinical trials remain the gold standard approach to defining clinical utility of local and systemic therapeutic interventions, the broader adoption of comprehensive tumour profiling and novel trial designs coupled with RWE may allow patient and physician autonomy to be appropriately balanced with broader assessments of safety and overall societal benefit.

Aging is associated with a rapid decline in frequency, alterations in subset composition, and enhanced Th2 response in CD1d-restricted NKT cells from human peripheral blood.

NKT cells are important for initiating and regulating immune responses. We investigated the age-related changes in the CD1d-restricted semi-invariant NKT (iNKT) cells in peripheral blood of healthy adults. The iNKT cell frequency was 2.5- to 10.7-fold less in healthy elderly subjects (61 years and over) compared to the healthy young subjects (20-40 years, p<0.001). This age-related decline in iNKT cells was observed both in freshly isolated PBMC and in cultures where iNKT cells were enriched by alpha-GalCer stimulation using either the Valpha24/Vbeta11 TCR antibody pair or the CD1d-tetramer as the iNKT cell marker. The decline in frequency was associated with an alteration in the iNKT cell subset compositions: an increase in the proportion of CD4+ subset and a decrease in the proportion of CD4/CD8 double-negative (DN) subset. The age-related decline in iNKT cells and changes in subset composition were independent from the age-related changes of conventional T cells/T cell subsets. Additionally, there was a Th1 to Th2 shift in the cytokine response profile from iNKT cells with aging. We conclude that aging is associated with a significant decline in iNKT cell frequency in peripheral blood, accompanied with alterations in subset composition and cytokine response profile.