Advances in spatial transcriptomics and its applications in cancer research

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 20, 2024

Abstract Malignant tumors have increasing morbidity and high mortality, their occurrence development is a complicate process. The of sequencing technologies enabled us to gain better understanding the underlying genetic molecular mechanisms in tumors. In recent years, spatial transcriptomics been developed rapidly allow quantification illustration gene expression context tissues. Compared with traditional technologies, not only detect levels cells, but also inform location genes within tissues, cell composition biological interaction between cells. Here we summarize tools its application cancer research. We discuss limitations challenges current approaches, as well future prospects.

Language: Английский

---

State-of-the-Art and Upcoming Innovations in Pancreatic Cancer Care: A Step Forward to Precision Medicine

Cancers, Journal Year: 2023, Volume and Issue: 15(13), P. 3423 - 3423

Published: June 30, 2023

Pancreatic cancer remains a social and medical burden despite the tremendous advances that medicine has made in last two decades. The incidence of pancreatic is increasing, it continues to be associated with high mortality morbidity rates. difficulty early diagnosis (the lack specific symptoms biomarkers at stages), aggressiveness disease, its resistance systemic therapies are main factors for poor prognosis cancer. only curative treatment surgery, but vast majority patients have advanced disease time diagnosis. surgery among most challenging surgical procedures, recent improvements techniques, careful patient selection, availability minimally invasive techniques (e.g., robotic surgery) dramatically reduced surgery. Patients who not candidates may benefit from locoregional therapy. In some cases whom marginal resection feasible), therapy considered bridge allow downstaging cancer; other metastatic disease), standard approach goal prolonging survival. complexity requires personalized multidisciplinary choose best each clinical situation. aim this article provide literature review available treatments different stages

Language: Английский

---

Activation of the PI3K/AKT signaling pathway by ARNTL2 enhances cellular glycolysis and sensitizes pancreatic adenocarcinoma to erlotinib

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: March 8, 2024

Abstract Background Pancreatic adenocarcinoma (PC) is an aggressive malignancy with limited treatment options. The poor prognosis primarily stems from late-stage diagnosis and when the disease has become therapeutically challenging. There urgent need to identify specific biomarkers for cancer subtyping early detection enhance both morbidity mortality outcomes. addition of EGFR tyrosine kinase inhibitor (TKI), erlotinib, gemcitabine chemotherapy first-line patients advanced pancreatic slightly improved However, restricted clinical benefits may be linked absence well-characterized criteria stratification dependable prediction effectiveness. Methods results We examined levels various hallmarks identified glycolysis as primary risk factor overall survival in PC. Subsequently, we developed a glycolysis-related score (GRS) model accurately distinguish PC high GRS. Through silico screening 4398 compounds, discovered that erlotinib had strongest therapeutic high-GRS patients. Furthermore, ARNTL2 novel prognostic biomarker predictive responsiveness Inhibition expression reduced efficacy, whereas increased cell sensitivity erlotinib. Validation vivo using patient-derived xenografts (PDX-PC) varying demonstrated monotherapy effectively halted tumor progression PDX-PC models expression. In contrast, lacking did not respond favorably treatment. Mechanistically, ARNTL2/E2F1 axis-mediated cellular sensitizes cells by activating PI3K/AKT signaling pathway. Conclusions Our investigations have indicator sensitivity. These will help erlotinib-responsive cases improve findings contribute advancement precision oncology, enabling more accurate targeted interventions.

Language: Английский

---

Advance in the role of chemokines/chemokine receptors in carcinogenesis: Focus on pancreatic cancer

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 967, P. 176357 - 176357

Published: Feb. 1, 2024

Language: Английский

---

HMGA2 alleviates ferroptosis by promoting GPX4 expression in pancreatic cancer cells

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(3)

Published: March 16, 2024

Abstract Pancreatic cancer is one of the most malignant tumor types and characterized by high metastasis ability a low survival rate. As chromatin-binding protein, HMGA2 widely overexpressed considered an oncogene with various undefined regulatory mechanisms. Herein, we demonstrated that highly expressed in pancreatic tissues, mainly distributed epithelial cells, represents subtype epithelial–mesenchymal transition. Deletion inhibits malignancy through cell proliferation, metastasis, xenograft growth vivo. Moreover, enhanced cellular redox status inhibiting reactive oxygen species promoting glutathione production. Importantly, ferroptotic death was significantly ameliorated cells overexpressing HMGA2. Conversely, deletion exacerbated ferroptosis. Mechanistically, activated GPX4 expression transcriptional translational regulation. binds promotes cis-element modification promoter region gene enhancing enhancer activity increased H3K4 methylation H3K27 acetylation. Furthermore, stimulated protein synthesis via mTORC1-4EBP1 -S6K signaling axes. The overexpression alleviated decrease levels resulting from pharmacologic inhibition mTORC1. compared control, more strongly reduced phosphorylation 4EBP1 S6K. A strong positive correlation between confirmed using immunohistochemical staining. We also mitigated sensitivity to combination treatment ferroptosis inducer mTORC1 or gemcitabine. In summary, our results revealed mechanism which coordinates underscores potential value targeting treatment.

Language: Английский

---

Pancreatic Ductal Adenocarcinoma (PDAC): A Review of Recent Advancements Enabled by Artificial Intelligence

Cancers, Journal Year: 2024, Volume and Issue: 16(12), P. 2240 - 2240

Published: June 17, 2024

Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most formidable challenges in oncology, characterized by its late detection and poor prognosis. Artificial intelligence (AI) machine learning (ML) are emerging as pivotal tools revolutionizing PDAC care across various dimensions. Consequently, many studies have focused on using AI to improve standard care. This review article attempts consolidate literature from past five years identify high-impact, novel, meaningful focusing their transformative potential management. Our analysis spans a broad spectrum applications, including but not limited patient risk stratification, early detection, prediction treatment outcomes, thereby highlighting AI’s role enhancing quality precision By categorizing into discrete sections reflective patient’s journey screening diagnosis through survivorship, this offers comprehensive examination AI-driven methodologies addressing multifaceted PDAC. Each study is summarized explaining dataset, ML model, evaluation metrics, impact has improving PDAC-related outcomes. We also discuss prevailing obstacles limitations inherent application within context, offering insightful perspectives future directions innovations.

Language: Английский

---

Overcoming therapy resistance in pancreatic cancer: New insights and future directions

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 229, P. 116492 - 116492

Published: Aug. 15, 2024

Pancreatic adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer deaths by 2030 and this mostly due therapy failure. Limited treatment options resistance standard-of-care (SoC) therapies makes PDAC one types with poorest prognosis survival rates [1,2]. tumors are renowned for their poor response therapeutic interventions including targeted therapies, chemotherapy radiotherapy. Herein, we review hallmarks in current strategies aiming tackle escape mechanisms re-sensitize cells therapy. We will further provide insights on recent advances field drug discovery, nanomedicine, disease models that setting ground future research.

Language: Английский

---

Cancer‐Associated Fibroblast‐Secreted Exosomes Regulate Macrophage Polarization in Pancreatic Cancer via the NOD1 Pathway

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(1)

Published: Jan. 1, 2025

ABSTRACT Metastasis is a major cause of poor prognosis pancreatic cancer. Exosomes (Exos) regulate cancer progression by modulating macrophage polarization. This study aimed to investigate the effects cancer‐associated fibroblast (CAF)‐released Exos on polarization in and molecular mechanisms. THP‐1 cells or xenografted tumor mice were treated with from CAFs, was analyzed using quantitative real‐time PCR (qPCR) flow cytometry. cocultured BXPC‐3 cells, metastasis Transwell assay scratch test. Exosomal PTGS2 detected qPCR, NOD1 pathway evaluated western blot analysis. The results showed that promoted M2‐type inhibited M1‐type polarization, then facilitated cell migration, invasion, epithelial‐mesenchymal transition. expression increased Exo‐treated macrophages, its knockdown CAFs M2 M1 Moreover, via PTGS2, inhibition reversed caused Exos. Additionally, required M1/M2 vivo mediated In conclusion, CAF‐secreted carrying activate pathway, thereby promoting metastasis, providing evidence CAF‐Exos accelerating progression.

Language: Английский

---

Defective homologous recombination and genomic instability predict increased responsiveness to carbon ion radiotherapy in pancreatic cancer

npj Precision Oncology, Journal Year: 2025, Volume and Issue: 9(1)

Published: Jan. 17, 2025

Pancreatic ductal adenocarcinoma (PDAC) is notably resistant to conventional chemotherapy and radiation treatment. However, clinical trials indicate that carbon ion radiotherapy (CIRT) with concurrent gemcitabine effective for unresectable locally advanced PDAC. This study aimed identify patient characteristics predictive of CIRT response. We utilized a panel human PDAC cell lines diverse genetic profiles determine their sensitivity compared γ-rays, assessing relative biological effectiveness (RBE) at 10% survival, which ranged from 1.96 3.04. Increased radiosensitivity was linked impaired DNA double-strand break (DSB) repair, particularly in deficiencies the homologous recombination (HR) repair pathway and/or elevated genomic instability replication stress. Furthermore, pretreatment HR inhibitor B02 significantly enhanced radioresistant line when irradiated spread-out Bragg peak but not entry position beam. These findings suggest tumors mutations or high stress are more likely benefit while minimizing normal tissue toxicity.

Language: Английский

---

Current Approaches for the Curative-Intent Surgical Treatment of Pancreatic Ductal Adenocarcinoma

Cancers, Journal Year: 2023, Volume and Issue: 15(9), P. 2584 - 2584

Published: April 30, 2023

Radical resection is the only curative treatment for pancreatic cancer. However, up to 20% of patients are considered eligible surgical at time diagnosis. Although upfront surgery followed by adjuvant chemotherapy has become gold standard resectable cancer there numerous ongoing trials aiming compare clinical outcomes various strategies (e.g., or neoadjuvant with subsequent resection). Neoadjuvant best approach in borderline tumors. Individuals locally advanced disease now candidates palliative chemo- chemoradiotherapy; however, some may during course such treatment. When metastases found, qualified as unresectable. It possible perform radical metastasectomy selected cases oligometastatic disease. The role multi-visceral resection, which involves reconstruction major mesenteric veins, well known. Nonetheless, controversies terms arterial and reconstruction. Researchers also trying introduce personalized treatments. careful, preliminary selection other therapies should be based on tumor biology, among factors. Such play a key improving survival rates

Language: Английский

---