Global Disparities of Cancer and Its Projected Burden in 2050.

Importance: Cancer prevention and care efforts have been challenged by the COVID-19 pandemic and armed conflicts, resulting in a decline in the global Human Development Index (HDI), particularly in low- and middle-income countries. These challenges and subsequent shifts in health care priorities underscore the need to continuously monitor cancer outcome disparities and statistics globally to ensure delivery of equitable and optimal cancer prevention and care in uncertain times.

Objective: To measure the global burden of 36 cancers in 2022 by sex, age, and geographic location and to project future trends by 2050.

West African Genetic Ancestry, Neighborhood Deprivation, and Prostate Cancer.

Importance: Racial disparities in prostate cancer are likely the result of complex relationships between both socioeconomic and environmental factors captured by the neighborhood environment and genetic factors, including West African genetic ancestry. However, few studies have examined the combined role of neighborhood environment and genetic ancestry in developing lethal prostate cancer.

Objective: To examine the interactions between West African genetic ancestry and neighborhood deprivation in modifying prostate cancer risk and mortality.

Association of neighborhood gentrification with prostate cancer and immune markers in African American and European American men.

Background: Prior studies showed that neighborhood deprivation increases the risk of lethal prostate cancer. However, the role of neighborhood gentrification in prostate cancer development and outcome remains poorly understood. We examined the relationships of gentrification with prostate cancer and serum proteome-defined inflammation and immune function in a diverse cohort.

Diabetes-associated breast cancer is molecularly distinct and shows a DNA damage repair deficiency.

Diabetes commonly affects patients with cancer. We investigated the influence of diabetes on breast cancer biology using a 3-pronged approach that included analysis of orthotopic human tumor xenografts, patient tumors, and breast cancer cells exposed to diabetes/hyperglycemia-like conditions. We aimed to identify shared phenotypes and molecular signatures by investigating the metabolome, transcriptome, and tumor mutational burden.

Circulating trans fatty acids are associated with prostate cancer in Ghanaian and American men.

The association between fatty acids and prostate cancer remains poorly explored in African-descent populations. Here, we analyze 24 circulating fatty acids in 2934 men, including 1431 prostate cancer cases and 1503 population controls from Ghana and the United States, using CLIA-certified mass spectrometry-based assays. We investigate their associations with population groups (Ghanaian, African American, European American men), lifestyle factors, the fatty acid desaturase (FADS) genetic locus, and prostate cancer.

Systemic Inflammation Indices and Association with Prostate Cancer Survival in a Diverse Patient Cohort.

There is a lack of investigations assessing the performance of systemic inflammation indices as outcome predictive tools in African Americans with prostate cancer. This study aims to assess the relationships between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation (SII), and systemic inflammation response index (SIRI) with survival outcomes among 680 diverse men with prostate cancer. Routine blood results were collected from self-identified African American and European American patients.

Association of Neighborhood Deprivation With Prostate Cancer and Immune Markers in African American and European American Men.

Importance: Neighborhood variables may be factors in the excessive burden of prostate cancer among African American men.

Objective: To examine associations between neighborhood deprivation, circulating immune-oncology markers, and prostate cancer among African American and European American men.

Design, Setting, And Participants: A case-control study was conducted between January 1, 2005, and January 1, 2016.

Human herpesvirus 8 infection is associated with prostate cancer among IFNL4-ΔG carriers.

Background: The dinucleotide germline variant, rs368234815-ΔG, in the IFNL4 gene (IFNL4-ΔG) has been associated with prostate cancer among men at increased risk of sexually transmitted infections and reported to impair viral clearance. Human herpesvirus 8 (HHV-8) seropositivity has been associated with prostate cancer in Tobago.

Methods: We examined whether the association of HHV-8 with prostate cancer is IFNL4-ΔG-dependent among 728 IFNL4-ΔG-genotyped cases and 813 genotyped population-based controls from the NCI-Maryland Prostate Cancer Case-Control study.

Assessment of factors associated with PSA level in prostate cancer cases and controls from three geographical regions.

It is being debated whether prostate-specific antigen (PSA)-based screening effectively reduces prostate cancer mortality. Some of the uncertainty could be related to deficiencies in the age-based PSA cut-off thresholds used in screening. Current study considered 2779 men with prostate cancer and 1606 men without a cancer diagnosis, recruited for various studies in New Zealand, US, and Taiwan.

Urinary PGE-M in Men with Prostate Cancer.

Urinary PGE-M is a stable metabolite of prostaglandin E2 (PGE2). PGE2 is a product of the inflammatory COX signaling pathway and has been associated with cancer incidence and metastasis. Its synthesis can be inhibited by aspirin.

Urinary Thromboxane B2 and Lethal Prostate Cancer in African American Men.

Background: Thromboxane A2 (TXA2) is a platelet- and cyclooxygenase-derived eicosanoid that has been linked to metastasis. We investigated the role of TXA2 in the development of lethal prostate cancer in African American (AA) and European American (EA) men.

Methods: We measured urinary 11-dehydrothromboxane B2 (TXB2), a stable metabolite of TXA2, with mass spectrometry.

-ΔG is associated with prostate cancer among men at increased risk of sexually transmitted infections.

Sexually transmitted infections can reach the prostate gland where their harmful effects are mediated by innate immunity, including interferons. Humans are polymorphic for the germline dinucleotide variant, rs368234815-TT/ΔG, in the gene encoding interferon λ4. Since the ΔG allele has been linked to impaired viral clearance, we hypothesized that potential exposure to sexually transmitted pathogens, as assessed by the number of lifetime sexual partners, may increase prostate cancer risk in an ΔG-dependent manner.

ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming.

Metabolic reprogramming in breast tumors is linked to increases in putative oncogenic metabolites that may contribute to malignant transformation. We previously showed that accumulation of the oncometabolite, 2-hydroxyglutarate (2HG), in breast tumors was associated with MYC signaling, but not with isocitrate dehydrogenase (IDH) mutations, suggesting a distinct mechanism for increased 2HG in breast cancer. Here, we determined that D-2HG is the predominant enantiomer in human breast tumors and show that the D-2HG-producing mitochondrial enzyme, alcohol dehydrogenase, iron-containing protein 1 (ADHFE1), is a breast cancer oncogene that decreases patient survival.

Analysis of Tumor Biology to Advance Cancer Health Disparity Research.

Cancer mortality rates in the United States continue to decline. Reductions in tobacco use, uptake of preventive measures, adoption of early detection methods, and better treatments have resulted in improved cancer outcomes for men and women. Despite this progress, some population groups continue to experience an excessive cancer burden when compared with other population groups.

Inhibition of ERG Activity in Patient-derived Prostate Cancer Xenografts by YK-4-279.

Background/aim: The aim of the current study was to determine the effects of the ERG small-molecule inhibitor YK-4-279 on ERG prostate cancer patient-derived xenografts (PDX).

Materials And Methods: ERG activity was blocked using YK-4-279 in three subcutaneously-implanted ERG (LuCaP 23.1, 86.

Depletion of tyrosyl DNA phosphodiesterase 2 activity enhances etoposide-mediated double-strand break formation and cell killing.

DNA topoisomerase 2 (Top2) poisons, including common anticancer drugs etoposide and doxorubicin kill cancer cells by stabilizing covalent Top2-tyrosyl-DNA 5'-phosphodiester adducts and DNA double-strand breaks (DSBs). Proteolytic degradation of the covalently attached Top2 leaves a 5'-tyrosylated blocked termini which is removed by tyrosyl DNA phosphodiesterase 2 (TDP2), prior to DSB repair through non-homologous end joining (NHEJ). Thus, TDP2 confers resistance of tumor cells to Top2-poisons by repairing such covalent DNA-protein adducts, and its pharmacological inhibition could enhance the efficacy of Top2-poisons.

Combined experience of six independent laboratories attempting to create an Ewing sarcoma mouse model.

Ewing sarcoma (ES) involves a tumor-specific chromosomal translocation that produces the EWS-FLI1 protein, which is required for the growth of ES cells both in vitro and in vivo. However, an EWS-FLI1-driven transgenic mouse model is not currently available. Here, we present data from six independent laboratories seeking an alternative approach to express EWS-FLI1 in different murine tissues.

Ezrin Inhibition Up-regulates Stress Response Gene Expression.

Ezrin is a member of the ERM (ezrin/radixin/moesin) family of proteins that links cortical cytoskeleton to the plasma membrane. High expression of ezrin correlates with poor prognosis and metastasis in osteosarcoma. In this study, to uncover specific cellular responses evoked by ezrin inhibition that can be used as a specific pharmacodynamic marker(s), we profiled global gene expression in osteosarcoma cells after treatment with small molecule ezrin inhibitors, NSC305787 and NSC668394.

Ezrin Enhances EGFR Signaling and Modulates Erlotinib Sensitivity in Non-Small Cell Lung Cancer Cells.

Ezrin is a scaffolding protein that is involved in oncogenesis by linking cytoskeletal and membrane proteins. Ezrin interacts with epidermal growth factor receptor (EGFR) in the cell membrane, but little is known about the effects of this interaction on EGFR signaling pathway. In this study, we established the biological and functional significance of ezrin-EGFR interaction in non-small cell lung cancer (NSCLC) cells.

YK-4-279 effectively antagonizes EWS-FLI1 induced leukemia in a transgenic mouse model.

Ewing sarcoma is an aggressive tumor of bone and soft tissue affecting predominantly children and young adults. Tumor-specific chromosomal translocations create EWS-FLI1 and similar aberrant ETS fusion proteins that drive sarcoma development in patients. ETS family fusion proteins and over-expressed ETS proteins are also found in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients.

Identification of Novel Ezrin Inhibitors Targeting Metastatic Osteosarcoma by Screening Open Access Malaria Box.

Ezrin is a member of the ERM (ezrin, radixin, moesin) family of proteins and functions as a linker between the plasma membrane and the actin cytoskeleton. Ezrin is a key driver of tumor progression and metastatic spread of osteosarcoma. We discovered a quinoline-based small molecule, NSC305787, that directly binds to ezrin and inhibits its functions in promoting invasive phenotype.