Major Cancer Types Research Articles

The Human Pathology Atlas for deciphering the prognostic features of human cancers

Cancer is one of the leading causes of mortality worldwide, highlighting the urgent need for a deeper molecular understanding and the development of personalized treatments. The present study aims to establish a solid association between gene expression and patient survival outcomes to enhance the utility of the Human Pathology Atlas for cancer research. In this updated analysis, we examined the expression profiles of 6918 patients across 21 cancer types. We integrated data from 10 independent cancer cohorts, creating a cross-validated, reliable collection of prognostic genes. We applied systems biology approach to identify the association between gene expression profiles and patient survival outcomes. We further constructed prognostic regulatory networks for kidney renal clear cell carcinoma (KIRC) and liver hepatocellular carcinoma (LIHC), which elucidate the molecular underpinnings associated with patient survival in these cancers. We observed that gene expression during the transition from normal to tumorous tissue exhibited diverse shifting patterns in their original tissue locations. Significant correlations between gene expression and patient survival outcomes were identified in KIRC and LIHC among the major cancer types. Additionally, the prognostic regulatory network established for these two cancers showed the indicative capabilities of the Human Pathology Atlas and provides actionable insights for cancer research. The updated Human Pathology Atlas provides a significant foundation for precision oncology and the formulation of personalized treatment strategies. These findings deepen our understanding of cancer biology and have the potential to advance targeted therapeutic approaches in clinical practice. The Knut and Alice Wallenberg Foundation (72110), the China Scholarship Council (Grant No. 202006940003).

Abstract A019: Discovery of a potent and brain-penetrable tubulin inhibitor SB-216 that shows efficacy in primary tumor growth and brain metastasis

Abstract A major clinical challenge in cancer treatment is to prevent and treat metastatic disease. Despite the significant advancements in targeted therapy and immunotherapy, chemotherapeutic drugs, including taxanes, remain one of the mainline systemic treatment options for several major cancer types. However, the prolonged use of taxanes has been associated with the development of multidrug resistance, dose-limiting hematopoietic toxicity, and neurotoxicity, frequently presenting as persistent peripheral neuropathy. In addition, these drugs have limited blood-brain barrier penetration, and thus they are not effective in treating brain tumors or brain metastases from other cancer types, particularly breast cancer metastases. We have developed a new generation of tubulin inhibitors, termed colchicine binding site inhibitors (CBSIs). Unlike taxanes, these compounds bind to the colchicine site in tubulin, structurally less complex than taxanes which enables fine-tuning of physical-chemical properties, and shows the ability to overcome acquired drug resistance to existing taxane drugs. One of the best inhibitors in this class of compounds is SB-216. We have solved the high-resolution crystal structure of SB-216 in a complex with tubulin protein (PDB: 6X1F) and confirmed its mode of action. Extensive preclinical evaluations of SB-216 in a number of tumor models, including taxane-resistant prostate cancer, melanoma, ovarian cancer, and triple-negative breast cancer, indicated that SB-216 is highly potent in suppressing both primary tumor growth and tumor metastases. Importantly, SB-216 shows high brain penetration and shows efficacy in suppressing brain metastases from triple-negative breast cancer. SB-216 also has good drug-like properties and shows strong promise as a new generation of tubulin inhibitor for systemic cancer treatments, not only in brain metastasis from non-CNS tumors but also potentially be useful for brain tumors such as glioma. The work is supported by NIH/NCI grants R01CA14876 and R01CA276152 and the DoD grant HT9425-23-1-0216. Citation Format: Kelli L. Adeleye, Satyanarayana Pochampally, Raisa Krutilina, Rui Wang, Junming Yue, Tiffany Seagroves, Duane D.Miller, Wei Li. Discovery of a potent and brain-penetrable tubulin inhibitor SB-216 that shows efficacy in primary tumor growth and brain metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A019.

Where should the cancer control interventions target: A geospatial hotspot analysis for major cancer mortality 2018-2022 in the U.S.

Identifying changes in geographical disparities of cancer mortality reveals locations where cancer prevention and control efforts should be focused/targeted. We use recent cancer surveillance data to demonstrate the geographical disparity of major cancer mortality rates in the US and its shift compared to previous data. This cross-sectional study used the 2018-2022 county-level mortality rates of colorectal, lung, breast and prostate cancer from the CDC mortality data. Counties with suppressed death counts were imputed by spatial regression models. Getis-Ord Gi* statistics were used to evaluate spatial clustering of county mortality. Identified hotspot counties were visualized and compared with literature for hotspot pattern change. A total of 3108 US mainland counties were included. Cancer mortality rates were significantly higher in 244 counties for colorectal, 456 for lung, 147 for breast and 180 for prostate. Hotspot areas were central Appalachia (for colorectal and lung), Lower Mississippi Delta (colorectal, breast and prostate), Midwest (colorectal and lung), north Michigan/Wisconsin (lung and prostate), north Florida (lung), and the West (prostate). West central Appalachia and Lower Mississippi Delta continue to be hotspots for major cancer types, while previously identified eastern North Carolina/Virginia hotspots shrunk, east Oklahoma and north Florida emerged as the new hotspot for lung cancer, and several hotspots emerged in the West for prostate cancer. This study updated the analyses for geospatial disparity in major cancers' mortality since 2018-illustrating recent changes in the disparity pattern and pinpointing areas that cancer prevention and control efforts should target.

REMR: Identification of RNA Editing-mediated MiRNA Regulation in Cancers

Dysregulation of adenosine-to-inosine (A-to-I) RNA editing has been implicated in cancer progression. However, a comprehensive understanding of how A-to-I RNA editing is incorporated into miRNA regulation to modulate gene expression in cancer remains unclear, given the lack of effective identification methods. To this end, we introduced an information theory-based algorithm named REMR to systematically identify 12,006 A-to-I RNA editing-mediated miRNA regulatory triplets (RNA editing sites, miRNAs, and genes) across ten major cancer types based on multi-omics profiling data from The Cancer Genome Atlas (TCGA). Through analyses of functional enrichment, transcriptional regulatory networks, and protein-protein interaction (PPI) networks, we showed that RNA editing-mediated miRNA regulation potentially affects critical cancer-related functions, such as apoptosis, cell cycle, drug resistance, and immunity. Furthermore, triplets can serve as biomarkers for classifying cancer subtypes with distinct prognoses or drug responses, highlighting the clinical relevance of such regulation. In addition, an online resource (http://www.jianglab.cn/REMR/) was constructed to support the convenient retrieval of our findings. In summary, our study systematically dissected the RNA editing-mediated miRNA regulations, thereby providing a valuable resource for understanding the mechanism of RNA editing as an epitranscriptomic regulator in cancer.

Biosynthesis-Encoded Lipogenic Acetyl-CoA Measurement Using NMR Reveals Glucose-Driven Lipogenesis and Glutamine's Alternative Roles in Kidney Cancer.

Fatty acid de novo synthesis (FADNS) is a critical process in lipogenesis that is characteristically altered in clear cell renal cell carcinoma (ccRCC), which is the major type of kidney cancer. An important challenge in studying the FADNS process has been the accurate measurement of cytosolic lipogenic acetyl-CoA (AcCoA), the precursor in FADNS, due to its compartmentalization within cells. Here, we describe a novel NMR-based method to decode the isotopic enrichment of lipogenic AcCoA, which, as we demonstrated, is encoded in the simple signal ratios of the geminal methyl groups of lanosterol during its biosynthesis. The approach was validated based on the independence of the tracer enrichment and species along with the expected FADNS modulation using differentially enriched tracers and a well-studied drug. Application of this technique to 786-O ccRCC cells showed that glucose may serve as a major carbon source for lipogenic AcCoA in FADNS at physiological nutrient concentrations, at odds with previous studies that indicated glutamine's dominant role through reductive carboxylation under higher nutrient conditions. Further investigation into glutamine's alternative roles in ccRCC cells suggested its major involvement in the bioenergetic TCA cycle, pyrimidine synthesis, and glutathione synthesis, which is also critical in ccRCC growth. The glutamine-dependent glutathione synthesis was also suggested as a possible metabolic vulnerability compared to normal kidney cells using a glutathione synthesis inhibitor. The current study provides a simple tool for studying an important aspect of lipid metabolism and suggests translational implications for targeting glucose-driven lipogenesis and glutamine-supported glutathione synthesis in ccRCC.

Preliminary Screening for Hereditary Breast and Ovarian Cancer Using an AI Chatbot as a Genetic Counselor: Clinical Study.

Hereditary breast and ovarian cancer (HBOC) is a major type of hereditary cancer. Establishing effective screening to identify high-risk individuals for HBOC remains a challenge. We developed a prototype of a chatbot system that uses artificial intelligence (AI) for preliminary HBOC screening to determine whether individuals meet the National Comprehensive Cancer Network BRCA1/2 testing criteria. This study's objective was to validate the feasibility of this chatbot in a clinical setting by using it on a patient population that visited a hospital. We validated the medical accuracy of the chatbot system by performing a test on patients who consecutively visited the Kanagawa Cancer Center. The participants completed a preoperation questionnaire to understand their background, including information technology literacy. After the operation, qualitative interviews were conducted to collect data on the usability and acceptability of the system and examine points needing improvement. A total of 11 participants were enrolled between October and December 2020. All of the participants were women, and among them, 10 (91%) had cancer. According to the questionnaire, 6 (54%) participants had never heard of a chatbot, while 7 (64%) had never used one. All participants were able to complete the chatbot operation, and the average time required for the operation was 18.0 (SD 5.44) minutes. The determinations by the chatbot of whether the participants met the BRCA1/2 testing criteria based on their medical and family history were consistent with those by certified genetic counselors (CGCs). We compared the medical histories obtained from the participants by the CGCs with those by the chatbot. Of the 11 participants, 3 (27%) entered information different from that obtained by the CGCs. These discrepancies were caused by the participant's omissions or communication errors with the chatbot. Regarding the family histories, the chatbot provided new information for 3 (27%) of the 11 participants and complemented information for the family members of 5 (45%) participants not interviewed by the CGCs. The chatbot could not obtain some information on the family history of 6 (54%) participants due to several reasons, such as being outside of the scope of the chatbot's interview questions, the participant's omissions, and communication errors with the chatbot. Interview data were classified into the following: (1) features, (2) appearance, (3) usability and preferences, (4) concerns, (5) benefits, and (6) implementation. Favorable comments on implementation feasibility and comments on improvements were also obtained. This study demonstrated that the preliminary screening system for HBOC using an AI chatbot was feasible for real patients.

Deep Diving Into the Fusion Across Cancer Types in the Indian Population From Formalin-Fixed Paraffin-Embedded RNA-Exome Data: A Road to Discovering Novel Rearrangements With Clinical Relevance.

Gene fusions are critical oncogenic mutations that drive cancer development and serve as diagnostic and prognostic biomarkers. Despite the increasing cancer burden in India, large-scale analyses of molecular landscapes, particularly gene fusions, have been relatively scarce. This retrospective study used RNA-exome data from 1,392 Indian patients with cancer across 15 major cancer types to explore gene fusions. The study used a comprehensive framework that integrated open-source and proprietary tools to detect gene fusions from formalin-fixed paraffin-embedded tumor samples. The process involved RNA extraction, RNA-exome library preparation, and analysis using tools such as FastQC, DRAGEN RNA Pipeline, STAR-Fusion, and FusionInspector. We validated and filtered potential false-positive fusion calls using AGFusion and FusionAnnotator to annotate fusion breakpoints and their functional impact through various in silico tools. The study found a notable prevalence of FGFR fusions across cancer types, especially FGFR3, with FGFR3::TACC3 as the most recurrent. Kinase fusions were prevalent in the cohort accounting for 37% of incidence in the patients. We also identified 91 novel potential driver fusions, including those involving FGFR2, MET, ESR1, and PDGFRA. This study underscores the critical role of gene fusions as biomarkers in cancer, extending beyond fusion-driven malignancies to encompass all cancer types. Gene fusions serve as both diagnostic markers and tumor-agnostic therapeutic targets within the current cancer treatment paradigm. Our insights into the prevalence of oncogenic drivers and novel targets expand the understanding of gene fusions, shedding new light on their mechanisms and clinical implications.

Intricate roles of estrogen and estrogen receptors in digestive system cancers: a systematic review.

Gender disparities are evident across different types of digestive system cancers, which are typically characterized by a lower incidence and mortality rate in females compared to males. This finding suggests a potential protective role of female steroid hormones, particularly estrogen, in the development of these cancers. Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors (ERs), including the classic (ERα and ERβ) and non-traditional ERs [G protein-coupled estrogen receptor (GPER)]. Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers. In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers, including hepatocellular, pancreatic, esophageal, gastric, and colorectal carcinoma. Furthermore, we discuss the potential molecular mechanisms underlying ERα, ERβ, and GPER effects, and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs. The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved. Additionally, deciphering the intricate roles of estrogen, ERs, and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers, eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.

The diagnosis value of dual-energy computed tomography (DECT) multi-parameter imaging in lung adenocarcinoma and squamous cell carcinoma.

Lung cancer continues to pose a serious risk to human health. With a high mortality rate, non-small cell lung cancer (NSCLC) is the major type of lung cancer, making up to 85% of all cases of lung cancer. Lung adenocarcinoma (AC), and lung squamous cell carcinoma (SC) are the two primary types of NSCLC. Determining the pathological type of NSCLC is important in establishing the most effective treatment method. Dual-energy computed tomography (DECT) multi-parameter imaging is an imaging technology that provides accurate and reliable disease diagnosis, and its uses are utilized for the combined diagnostic efficacy of AC and SC. The purpose of this study was to investigate the diagnostic value of spectral parameters of DECT in efficacy to AC and SC, and their combined diagnostic efficacy was also analyzed. We conducted a retrospective analysis of clinical and imaging data for 36 patients diagnosed with SC and 35 patients with AC. These patients underwent preoperative DECT chest scans, encompassing both arterial and venous phases, at our hospital from December 2020 to April 2022. The tumor diameter, water concentration (WC), iodine concentration (IC), normalized iodine concentration (NIC), Z effective (Zeff), and slope of the curve (K) in lesions were evaluated during two scanning phases in the two separate pathological types of lung cancers. The differences in parameters between these two types of lung cancers were statistically analyzed. In addition, receiver operating characteristic (ROC) curves were performed for these parameters to distinguish between SC and AC. In a univariate analysis involving 71 lung cancer patients, the results from Zeff, IC, NIC, and K from the AC's arterial and venous phase images were more elevated than those from the SC (P < 0.05). In contrast, the WC results were lower than those from SC (P < 0.05). The area under the ROC curve (AUC) for multi-parameter joint prediction typing was 0.831, with a corresponding sensitivity of 63.9% and specificity of 94.3%. It is possible to distinguish between central SC and AC using the spectrum characteristics of DECT-enhanced scanning (Zeff, IC, NIC, K, WC, and tumor diameter). Diagnostic effectiveness can be greatly improved when multiple variables are included.

The association between heart failure diagnosis and the incidence of cancer: a longitudinal analysis of the United Kingdom Biobank

Abstract Background Heart failure (HF) and cancer represent prevalent chronic conditions with a high burden of disease worldwide. Several studies have shown a high frequency of coexistence of these two entities, highlighting a potential bidirectional association. However, few longitudinal studies have explored whether patients with HF have a significantly increased risk of cancer and if comorbidity profiles affect this risk. Purpose To explore the association between incident HF diagnosis and cancer development in UK Biobank participants after adjustment by potential confounders. Methods We conducted a retrospective cohort study in UK Biobank. HF and cancer diagnoses were determined using diagnoses and patient reports. We evaluated breast, liver, lung, prostate, colorectal, uterus, and hematological cancer. Individuals with a history of HF or cancer diagnosed before the baseline assessment were excluded. The primary exposure was incident HF diagnosis after enrollment, and the primary outcome was incident cancer during follow-up. Multivariate Cox proportional hazard regression models using time-varying covariates were used to calculate hazard ratios (HR) for the explored associations with overall cancer and by major cancer type. A Bonferroni-corrected p-value &amp;lt; 0.003 was considered statistically significant to control for family-wise error rate. Results 476,652 patients were analyzed (mean age: 56.3 years; 57.8% females). Over a median follow-up of 13.7 years, 12,461 (2.6%) developed HF, and 34,452 (7.2%) were diagnosed with cancer. Incident HF was significantly associated with increased overall cancer risk (HR 1.34, 95% CI 1.22–1.48. p&amp;lt;0.001), as well as lung (HR 1.30, 95% CI 1.18–1.43), and hematological cancers (HR 1.54, 95% CI 1.25–1.91. p&amp;lt;0.001) (Figure). Conclusion Despite sharing multiple comorbidities and risk factors, incident HF remained significantly associated with a higher cancer risk even after multivariable adjustment by relevant confounders. Nevertheless, confounding bias and especially detection bias, cannot be ruled out in the present analysis. Further research is necessary to validate these findings and elucidate the mechanisms underlying this association.Figure

Peptide-Conjugated Vascular Endothelial Extracellular Vesicles Encapsulating Vinorelbine for Lung Cancer Targeted Therapeutics.

Lung cancer is one of the major cancer types and poses challenges in its treatment, including lack of specificity and harm to healthy cells. Nanoparticle-based drug delivery systems (NDDSs) show promise in overcoming these challenges. While conventional NDDSs have drawbacks, such as immune response and capture by the reticuloendothelial system (RES), extracellular vesicles (EVs) present a potential solution. EVs, which are naturally released from cells, can evade the RES without surface modification and with minimal toxicity to healthy cells. This makes them a promising candidate for developing a lung-cancer-targeting drug delivery system. EVs isolated from vascular endothelial cells, such as human umbilical endothelial-cell-derived EVs (HUVEC-EVs), have shown anti-angiogenic activity in a lung cancer mouse model; therefore, in this study, HUVEC-EVs were chosen as a carrier for drug delivery. To achieve lung-cancer-specific targeting, HUVEC-EVs were engineered to be decorated with GE11 peptides (GE11-HUVEC-EVs) via a postinsertional technique to target the epidermal growth factor receptor (EGFR) that is overexpressed on the surface of lung cancer cells. The GE11-HUVEC-EVs were loaded with vinorelbine (GE11-HUVEC-EVs-Vin), and then characterized and evaluated in in vitro and in vivo lung cancer models. Further, we examined the binding affinity of ABCB1, encoding P-glycoprotein, which plays a crucial role in chemoresistance via the efflux of the drug. Our results indicate that GE11-HUVEC-EVs-Vin effectively showed tumoricidal effects against cell and mouse models of lung cancer.

A genetically informed study reveals modifiable pathways in skin cancer

BackgroundIdentifying modifiable risk factors is essential for the prevention of skin cancer; however, establishing causality can be challenging in conventional epidemiological studies. This study aimed to determine the causal associations of potentially modifiable risk factors with skin cancer using Mendelian randomization (MR).MethodsGenetic instruments for 53 risk factors, including socioeconomic status, dietary and lifestyle factors, anthropometric measures, medication use, and comorbidities, were identified from previous genome-wide association studies. Two-sample MR analyses were performed using summary statistics for three major types of skin cancer: melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Findings were verified using multiple MR methods under different assumptions and replication datasets.ResultsGenetic liability to sunburn occasions, actinic keratosis, and prior skin cancers was associated with a higher risk of all three types of skin cancer, whereas genetic liability to vitiligo was associated with a lower risk. For specific skin cancer types, genetically predicted higher nevus counts and occupational class were associated with an increased risk of melanoma. Genetic liability to rheumatoid arthritis, type 2 diabetes, and increased physical activity were associated with a lower risk of BCC. Genetically predicated body mass index showed a negative association with BCC, and a positive association with SCC.ConclusionsOur study reaffirmed several previously established risk factors and identified novel potential risk factors for skin cancer. Further work is needed to unravel the biological pathways in different skin cancer types and translate our findings to inform public health policies.

Cancer-related Keywords in 2023: Insights from Text Mining of a Major Consumer Portal.

With the growing importance of monitoring cancer patients' internet usage, there is an increasing need for technology that expands access to relevant information through text mining. This study analyzed internet articles from portal sites in 2023 to identify trends in the information available to cancer patients and to derive meaningful insights. This study analyzed 19,578 news articles published on Naver, a major Korean portal site, from January 1, 2023, to December 31, 2023. Natural language processing, text mining, network analysis, and word cloud analysis were employed. The search term "am" (Korean for "cancer") was used to identify keywords related to cancer. In 2023, an average of 1,631 cancer-related articles were published monthly, with a peak of 1,946 in September and a low of 1,371 in February. A total of 132,456 keywords were extracted, with "cure" (2,218 occurrences), "lung cancer" (1,652), and "breast cancer" (1,235) being the most frequent. Term frequency-inverse document frequency analysis ranked "struggle" (1064.172) as the most significant keyword, followed by "lung cancer" (839.988) and "breast cancer" (744.840). Network analysis revealed four distinct clusters focusing on treatment, celebrity-related issues, major cancer types, and cancer-causing factors. The analysis of cancer-related keywords in 2023 indicates that news articles often prioritize gossip over essential information. These findings provide foundational data for future policy directions and strategies to address misinformation. This study underscores the importance of understanding the nature of cancer-related information consumed by the public and offers insights to guide official policies and healthcare practices.

Chromatin interaction maps identify oncogenic targets of enhancer duplications in cancer.

As a major type of structural variants, tandem duplication plays a critical role in tumorigenesis by increasing oncogene dosage. Recent work has revealed that noncoding enhancers are also affected by duplications leading to the activation of oncogenes that are inside or outside of the duplicated regions. However, the prevalence of enhancer duplication and the identity of their target genes remains largely unknown in the cancer genome. Here, by analyzing whole-genome sequencing data in a non-gene-centric manner, we identify 881 duplication hotspots in 13 major cancer types, most of which do not contain protein-coding genes. We show that the hotspots are enriched with distal enhancer elements and are highly lineage-specific. We develop a HiChIP-based methodology that navigates enhancer-promoter contact maps to prioritize the target genes for the duplication hotspots harboring enhancer elements. The methodology identifies many novel enhancer duplication events activating oncogenes such as ESR1, FOXA1, GATA3, GATA6, TP63, and VEGFA, as well as potentially novel oncogenes such as GRHL2, IRF2BP2, and CREB3L1 In particular, we identify a duplication hotspot on Chromosome 10p15 harboring a cluster of enhancers, which skips over two genes, through a long-range chromatin interaction, to activate an oncogenic isoform of the NET1 gene to promote migration of gastric cancer cells. Focusing on tandem duplications, our study substantially extends the catalog of noncoding driver alterations in multiple cancer types, revealing attractive targets for functional characterization and therapeutic intervention.

Trends in 5-year cancer survival disparities by race and ethnicity in the US between 2002–2006 and 2015–2019

Racial and ethnic disparities persist in cancer survival rates across the United States, despite overall improvements. This comprehensive analysis examines trends in 5-year relative survival rates from 2002–2006 to 2015–2019 for major cancer types, elucidating differences among racial/ethnic groups to guide equitable healthcare strategies. Data from the SEER Program spanning 2000–2020 were analyzed, focusing on breast, colorectal, prostate, lung, pancreatic cancers, non-Hodgkin lymphoma, acute leukemia, and multiple myeloma. Age-standardized relative survival rates were calculated to assess racial (White, Black, American Indian/Alaska Native, Asian/Pacific Islander) and ethnic (Hispanic, Non-Hispanic) disparities, utilizing period analysis for recent estimates and excluding cases identified solely through autopsy or death certificates. While significant survival improvements were observed for most cancers, notable disparities persisted. Non-Hispanic Blacks exhibited the largest gain in breast cancer survival, with an increase of 5.2% points (from 77.6 to 82.8%); however, the survival rate remained lower than that of Non-Hispanic Whites (92.1%). Colorectal cancer survival declined overall (64.7–64.1%), marked by a 6.2% point drop for Non-Hispanic American Indian/Alaska Natives (66.3–60.1%). Prostate cancer survival declined across all races, with Non-Hispanic American Indian/Alaska Natives showing a decrease of 7.7% points (from 96.9 to 89.2%). Lung cancer, acute leukemia, and multiple myeloma showed notable increases across groups. Substantial racial/ethnic disparities in cancer survival underscore the notable need for tailored strategies ensuring equitable access to advanced treatments, particularly addressing significant trends in colorectal and pancreatic cancers among specific minority groups. Careful interpretation of statistical significance is warranted given the large dataset.

Assessing Breast Cancer through Tumor Microenvironment Mapping of Collagen and Other Biomolecule Spectral Fingerprints─A Review.

Breast cancer is a major challenge in the field of oncology, with around 2.3 million cases and around 670,000 deaths globally based on the GLOBOCAN 2022 data. Despite having advanced technologies, breast cancer remains the major type of cancer among women. This review highlights various collagen signatures and the role of different collagen types in breast tumor development, progression, and metastasis, along with the use of photoacoustic spectroscopy to offer insights into future cancer diagnostic applications without the need for surgery or other invasive techniques. Through mapping of the tumor microenvironment and spotlighting key components and their absorption wavelengths, we emphasize the need for extensive preclinical and clinical investigations.

Pan-Cancer Single-Cell Analysis Revealing the Heterogeneity of Cancer-Associated Fibroblasts in Skin Tumors.

Cancer-Associated Fibroblasts (CAFs) constitute a heterogeneous group of cells critical for the remodeling of the tumor microenvironment (TME). Given their significant impact on tumor progression, particularly in skin cancers, a deeper understanding of their characteristics and functions is essential. This study employed a single-cell transcriptomic analysis to explore the diversity of CAFs within three major types of skin cancer: basal cell carcinoma, melanoma, and head and neck squamous cell carcinoma. We applied analytical techniques, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), pseudotime tracking, metabolic profiling, and stemness assessment to delineate and define the functional attributes of identified CAF subgroups. Our analysis successfully delineated nine distinct CAF subgroups across the studied tumor types. Of particular interest, we identified a novel CAF subtype, designated as C0, exclusive to basal cell carcinoma. This subtype exhibits phenotypic traits associated with invasive and destructive capabilities, significantly correlating with the progression of basal cell carcinoma. The identification of this subgroup provides new insights into the role of CAFs in cancer biology and opens avenues for targeted therapeutic strategies. A pan-cancer analysis was performed on three cancers, BCC, MA, and HNSCC, focusing on tumor fibroblasts in TME. Unsupervised clustering categorized CAF into nine subpopulations, among which the C0 subpopulation had a strong correspondence with BCC-CAF and an invasive- destructive-related phenotype.

Recent Advancements in Drug Delivery System in Lung Cancer

Eliminating the fact that the use of free pharmaceuticals in conventional dosage forms usually involves difficulties in hitting the target site at the appropriate dose after or during a correct time period, medication targeting specific organs and tissues became one of the century's most important initiatives. Thus, finding new drug delivery strategies and modes of action are lines of battle. Difficulties are still encountered with radiation therapy to accurately track the movements of lung tumors while treatments are being admitted. The development of MRI-linac hybrid system prototypes offers the possibility of real-time, ionization-free tumor imaging. This study assesses how well lung tumor tracking algorithms function on five healthy participants' cine-MRI sagittal images. The targets were vascular structures that could be seen. Lung cancer is the leading cause of mortality in the world. This is one of the heterogeneous diseases that include, at the basic level, two main subtypes: small cell lung cancer and non-small cell lung cancer. Less than 20% of patients with LC survive for 5 years on average despite recent improvements in treatment. The effectiveness of existing therapeutic techniques is impaired because of severe off-target effects and innate or acquired medication resistance. The two major types of lung cancers are SCLC and NSCLC; among these, the former is the most frequently diagnosed. Lung cancers account for the highest mortality rate due to cancer. The application of nanomedicines can partially overcome the failures that are associated with the anticancer therapies against NSCLC. One of the nanoparticle subfields that hold out much promise for better delivery while ensuring stability and sufficient bioavailability of administered anticancer medications is nanomedicine.

Abstract A081: Comprehensive examination of disparities in cancer incidences by race, gender, and age over 65 years in Alabama's Black belt counties, USA

Abstract In the United States, significant disparities persist in cancer incidence, mortality, and treatment outcomes, particularly among Black populations. Despite advances in medical care, disparities continue to challenge efforts to achieve health equity. Understanding and addressing these complex issues are imperative to ensure that all individuals, regardless of race or ethnicity, have equal access to effective cancer prevention, diagnosis, and treatment. Alabama stands out as the leading state among the top ten in terms of densely populated Black Belt counties in the United States. With 67 counties in total, Alabama is home to 24 designated Black Belt counties. Given this concentration, Alabama becomes a key focus for comprehending cancer disparities. The ongoing research seeks to examine the occurrence of various types of cancer among the predominant racial groups in the United States, focusing particularly on the Black Belt counties of Alabama. Data on cancer occurrences, obtained from the database of National Cancer Institute (NIH) and the Centers for Disease Control and Prevention (CDC), offer insights into cancer incidences among various demographic groups, age categories, and specific types of cancer spanning the last five years (2016-2020). Analysis of the data, focusing on patients aged 65 years and older, was performed using GraphPad Prism 5 software. Graphs were created to visually represent and interpret the data regarding incidences per 100,000 populations. We observe significantly elevated incidences of major cancer types such as prostate, colon, lung, stomach, pancreas, and liver among Black males, and similarly heightened rates of uterus, cervix, stomach, pancreas, and kidney cancers among Black females, when compared to white populations. Notably, within Alabama's Black Belt regions, only a small number of counties have reported incidences of cancer regardless of gender and cancer types, except for prostate cancer in males and breast cancer in females. Moreover, in certain Black Belt counties, rates of colon and lung cancer (in both males and females), as well as prostate cancer in males and breast cancer in females, are exceptionally elevated compared to both the statewide average in Alabama and even the national average in the United States. Generally, females tend to have lower rates of cancer across various types compared to males. In conclusion, factors contributing to these disparities include genetic predispositions, socioeconomic status, healthcare accessibility, systemic biases, and cultural influences. Further investigations, including molecular screening studies, are imperative to corroborate these health disparities and foster community-wide cancer awareness and public health initiatives. Citation Format: Faith Onomeh, Anathbandhu Chaudhuri. Comprehensive examination of disparities in cancer incidences by race, gender, and age over 65 years in Alabama's Black belt counties, USA [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A081.

Trends in Cancer Incidence and Mortality in US Adolescents and Young Adults, 2016-2021.

(1) Background: The incidence rate of early onset-cancer (<50) has increased since 1995. Among younger people, cancers in AYAs (aged 15-39 y) are often biologically distinct tumors from those treated in the pediatric and older adult population. The current study describes trends in the United States for the most recent years including the first year of the COVID-19 epidemic. We aimed to describe the recent incidence and mortality trends of cancers in AYAs (aged 15-39 y). (2) Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER 22) from 1 January 2016 to 31 December 2021. Age-adjusted incidence and mortality rates were assessed by SEER*Stat 8.4.3 for major cancer types by sex, race/ethnicity, age, and metropolitan/nonmetropolitan status. Time trends of age-adjusted incidence and mortality rates were examined by sex and metropolitan/nonmetropolitan status. (3) Results: Age-adjusted overall cancer incidence and mortality rates were stable during this study period. The age-adjusted incidence rates declined significantly for ependymoma, melanoma, carcinomas of lung, bronchus, and trachea, unspecified malignant neoplasms, and non-Hodgkin's lymphoma. Significant increases were found for gastrointestinal tract cancers and non-Kaposi sarcomas. The age-adjusted mortality rate decreased for acute myeloid leukemia, melanoma, carcinomas of liver and intrahepatic bile ducts, kidney and, in women, leukemia. For some cancers, rates differed by sex, race, ethnicity, and geography. Monitoring the rates and time trends of AYA cancer emphasizes the distinct health concern for this age group.