A therapeutic antibody targeting annexin-A1 inhibits cancer cell growth in vitro and in vivo

In this study we conducted the first investigation to assess the efficacy of a novel therapeutic antibody developed to target annexin-A1 (ANXA1). ANXA1 is an immunomodulatory protein which has been shown to be overexpressed in, and promote the development and progression of, several cancer types. In particular, high ANXA1 expression levels correlate with poorer overall survival in pancreatic and triple-negative breast cancers, two cancers with considerable unmet clinical need. MDX-124 is a humanised IgG1 monoclonal antibody which specifically binds to ANXA1 disrupting its interaction with formyl peptide receptors 1 and 2 (FPR1/2). Here we show that MDX-124 significantly reduced proliferation (p < 0.013) in a dose-dependent manner across a panel of human cancer cell lines expressing ANXA1. The anti-proliferative effect of MDX-124 is instigated by arresting cell cycle progression with cancer cells accumulating in the G1 phase of the cell cycle. Furthermore, MDX-124 significantly inhibited tumour growth in both the 4T1-luc triple-negative breast and Pan02 pancreatic cancer syngeneic mouse models (p < 0.0001). These findings suggest ANXA1-targeted therapy is a viable and innovative approach to treat tumours which overexpress ANXA1.</p

Cross-sectional associations between Angiotensin Converting Enzyme inhibitor use and cancer diagnosis in US adults

Purpose: The objective of the present study was to investigate the association between Angiotensin converting enzyme (ACE) inhibitor use and cancer incidence (overall, and breast, prostate, and colorectal cancers specifically) in a large representative sample of US adults. Methods: Cross-sectional data on cancer diagnosis, timing of cancer diagnosis, ACE inhibitor use, and other characteristics were extracted from 49 512 adults aged ≥ 20 years participating in the National Health and Nutrition Examination Survey (1999-2016). Multivariable-logistic and propensity score matching (PSM) regressions examined the relationship between pre-diagnosis use of ACE inhibitors and diagnosis of all cancers, and breast, prostate, and colorectal cancers specifically. Results: Overall, we observed an increased likelihood of cancer diagnosis [odds ratio (OR)=1.269, 95% confidence interval (CI): 1.088 to 1.480] among those who used ACE inhibitors compared to non-ACE inhibitor use, and for prostate cancer diagnosis (OR=1.438, 95% CI: 1.090 to 1.897), after adjusting for age, sex, body mass index, race/ethnicity, educational attainment, physical activity, alcohol drinking status, smoking status, and high blood pressure. PSM regression retrieved more conservative estimates such that the increased likelihood of cancer diagnosis was only observed when comparing ACE inhibitor users with non-drug users (OR=1.022, 95% CI: 1.016 to 1.027). Conclusion: Compared with non-ACE inhibitor use, ACE inhibitor use was associated with an increased risk of prostate cancer. In conclusion, in this large representative sample of US adults, it was found that ACE inhibitor use may have a marginal influence on some cancers