Research Silos in Cancer Disparities: Obstacles to Improving Clinical Outcomes for Underserved Patient Populations.

Despite much vaunted progress in cancer therapeutics and diagnostics, outcomes for many groups of non-White patients with cancer remain worse than those for their White compatriots. One reason for this is the lack of inclusion and representation of non-White patients in clinical trials, preclinical datasets, and among researchers, a shortfall that is gaining wide recognition within the cancer research community and the lay public. Several reviews and editorials have commented on the negative impacts of the status quo on progress in cancer research toward medical breakthroughs that help all communities and not just White patients with cancer. In this perspective, we describe the existence of research silos focused either on the impact of socioeconomic factors proceeding from systemic racism on cancer outcomes, or on genetic ancestry as it affects the molecular biology of cancer developing in specific patient populations. While both these research areas are critical for progress toward precision medicine equity, breaking down these silos will help us gain an integrated understanding of how race and racism impact cancer development, progression, and patient outcomes. Bringing this comprehensive approach to cancer disparities research will undoubtedly improve our overall understanding of how stress and environmental factors affect the molecular biology of cancer, which will lead to the development of new diagnostics and therapeutics that are applicable across cancer patient demographics.

High turnover of extracellular matrix reflected by specific protein fragments measured in serum is associated with poor outcomes in two metastatic breast cancer cohorts.

Increased extracellular matrix (ECM) formation and matrix metalloprotease (MMP)-mediated ECM degradation are parts of tumorgenesis and generates collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in serum with outcomes in two independent metastatic breast cancer (MBC) cohorts. ELISAs were used to measure C1M (MMP-generated type I collagen fragment), C3M (MMP-generated type III collagen fragment), C4M (MMP-generated type IV collagen fragment), and PRO-C3 (pro-peptide of type III collagen) in pretreatment serum from a phase 3 randomized clinical trial of second-line hormone therapy (HR+, n = 148), and a first-line trastuzumab-treated cohort (HER2+, n = 55). All sites of metastases were included. The collagen fragments were evaluated by Cox-regression analysis for their association with time-to-progression (TTP) and overall survival (OS). In the HR+ cohort, higher C1M and C3M levels (75th percentile cut-off) were associated with shorter TTP; all fragments were associated with shorter OS. In the HER2+ cohort, higher levels of all fragments were associated with shorter TTP; higher PRO-C3 was associated with shorter OS. In multivariate analysis of the HR+ trial for OS, higher levels of all fragments were significant for reduced OS when added separately (C1M HR = 2.1, p < 0.001; C3M HR = 1.8, p = 0.028; C4M HR = 1.8, p = 0.018; PRO-C3 HR = 1.8, p = 0.017); none other clinical covariates were significant. In conclusion, collagen fragments quantified in pretreatment serum was associated with shorter TTP and OS in two independent MBC cohorts receiving systemic therapy. If validated, quantification of ECM remodeling in serum has potential as prognostic and/or predictive biomarkers in MBC.