Tumor Microenvironment Remodeling in Gastrointestinal Cancer: Role of miRNAs as Biomarkers of Tumor Invasion DOI Creative Commons
Valeria Lucarini, Daniela Nardozi, Valentina Angiolini

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(6), P. 1761 - 1761

Published: June 19, 2023

Gastrointestinal (GI) cancers are the most frequent neoplasm, responsible for half of all cancer-related deaths. Metastasis is leading cause death from GI cancer; thus, studying processes that regulate cancer cell migration paramount importance development new therapeutic strategies. In this review, we summarize mechanisms adopted by cells to promote and subsequent metastasis formation highlighting key role tumor microenvironment components play in deregulating cellular pathways involved these processes. We, therefore, provide an overview different microRNAs promoting their as potential biomarkers prognosis, monitoring, diagnosis patients. Finally, relate possible use nutraceuticals a strategy targeting numerous invasiveness.

Language: Английский

The importance of preclinical models for cholangiocarcinoma drug discovery DOI
Florian Primavesi, Felix J. Krendl, Rupert Oberhuber

et al.

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Biliary tract cancer (BTC) comprises a clinically diverse and genetically heterogeneous group of tumors along the intra- extrahepatic biliary system (intrahepatic cholangiocarcinoma) gallbladder with common feature poor prognosis, despite increasing molecular knowledge associated genetic aberrations possible targeted therapies. Therefore, search for even more precise individualized therapies is ongoing preclinical tumor models are central to development such new approaches. The described in current review include simple advanced vitro vivo models, including cell lines, 2D monolayer, spheroid organoid cultures, 3D bioprinting, patient-derived xenografts, recently, machine-perfusion platform-based resected liver specimens. All these have individual advantages, disadvantages limitations that need be considered depending on desired application. In addition potential cost limitations, availability BTC types, time required model establishment growth success rate, differently reflect relevant characteristics as heterogeneity, spatial tumor-stroma microenvironment interactions, metabolic nutritional gradients immunological interactions. consequent combination different may improve clinical study outcomes by strengthening data basis.

Language: Английский

Citations

1
SERPINE1: Role in Cholangiocarcinoma Progression and a Therapeutic Target in the Desmoplastic Microenvironment DOI Creative Commons

Ralf‐Peter Czekay,

Craig E. Higgins,

Hasan Basri Aydin

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(10), P. 796 - 796

Published: May 7, 2024

A heterogenous population of inflammatory elements, other immune and nonimmune cells cancer-associated fibroblasts (CAFs) are evident in solid malignancies where they coexist with the growing tumor mass. In highly desmoplastic malignancies, CAFs prominent mesenchymal cell type microenvironment (TME), their presence abundance signal a poor prognosis. play major role progression various cancers by remodeling supporting stroma into dense, fibrotic matrix while secreting factors that promote maintenance cancer stem-like characteristics, survival, aggressive growth metastasis reduced sensitivity to chemotherapeutics. Tumors high stromal signatures more likely be associated drug resistance eventual relapse. Identifying molecular underpinnings for such multidirectional crosstalk among normal neoplastic types TME may provide new targets novel opportunities therapeutic intervention. This review highlights recent concepts regarding complexity CAF biology cholangiocarcinoma, cancer. The discussion focuses on heterogeneity, functionality resistance, contributions progressively stroma, involved signaling pathways participating genes.

Language: Английский

Citations

8
From mechanism to therapy: the journey of CD24 in cancer DOI Creative Commons
Kai Zhao,

Caifeng Wu,

Xiangjun Li

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 31, 2024

CD24 is a glycosylphosphatidylinositol-anchored protein that expressed in wide range of tissues and cell types. It involved variety physiological pathological processes, including adhesion, migration, differentiation, apoptosis. Additionally, has been studied extensively the context cancer, where it found to play role tumor growth, invasion, metastasis. In recent years, there growing interest as potential therapeutic target for cancer treatment. This review summarizes current knowledge CD24, its structure, function, cancer. Finally, we provide insights into clinical application discuss possible approaches development targeted therapies.

Language: Английский

Citations

6
Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights DOI Creative Commons
Xinyu Li, Haiying Zhao

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: Feb. 1, 2025

Abstract Secretory autophagy is a classical form of unconventional secretion that integrates with the secretory process, relying on highly conserved autophagy-related molecules and playing critical role in tumor progression treatment resistance. Traditional responsible for degrading intracellular substances by fusing autophagosomes lysosomes. However, uses signaling to mediate specific regulate microenvironment (TME). Cytoplasmic are preferentially secreted rather than directed toward lysosomal degradation, involving various selective mechanisms. Moreover, released convey biological signals TME, inducing immune dysregulation contributing drug Therefore, elucidating mechanisms underlying essential improving clinical treatments. This review systematically summarizes current knowledge autophagy, from initiation secretion, considering inter-tumor heterogeneity, explores its across different types. Furthermore, it proposes future research directions highlights unresolved challenges.

Language: Английский

Citations

0
PPIH is a novel diagnostic biomarker associated with immune infiltration in cholangiocarcinoma DOI Creative Commons
Jun Ye, Zhitao Chen, Chuan Zhang

et al.

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 7, 2025

Language: Английский

Citations

0
Targeting Integrin αvβ3 by Liposome-Tetrac Induce Dual Inhibitory Effects on Proliferation in Cholangiocarcinoma DOI

Fitria Sari Wulandari,

Linyi Huang,

Dana R. Crawford

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Abstract Cell surface receptors play vital roles in cancer growth and metastasis. Overexpressed integrin αvβ3 various cells crosstalk with the epidermal factor receptor further stimulated progression. Thyroid hormone binds to activate signal transduction cell proliferation. However, thyroxine (T4) deaminated analogue, tetraiodothyronine (tetrac), competes for binding on inhibits The current study investigated pathogenic effect of thyroid EGF cholangiocarcinoma potential a novel therapeutic strategy. Pathogenetic studies clinical samples revealed αvβ3, EGFR, (PD-ligand 1) PD-L1 related progression malignancy. expression. thyroxine-induced accumulated nuclei colocalized p300. Alternatively, increased nuclear accumulation β-catenin. Clinical evidence supported targeting EGFR therapy. Targeting liposome-tetrac inhibited EGFR-dependent transduction, expression, xenograft model. Liposome-tetrac its Dox-derivative targeted performed dual inhibitory effects inhibit growth. Our research provides significant findings that will inform enlighten field treatment.

Language: Английский

Citations

0
New platinum derivatives selectively cause double-strand DNA breaks and death in naïve and cisplatin-resistant cholangiocarcinomas DOI Creative Commons
Irene Olaizola, Mikel Odriozola‐Gimeno, Paula Olaizola

et al.

Journal of Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Patients with cholangiocarcinoma (CCA) have poor prognosis. Current cisplatin-based first-line chemotherapy offers limited survival benefits. Cisplatin induces single-strand DNA breaks, activating repair mechanisms that diminish its effectiveness. Here, we present the design, chemical synthesis, and therapeutic evaluation of a new generation chemotherapeutic agents (Aurkines) unique polyelectrophilic properties. These cause high frequency double-strand bypassing repair, promoting cancer cell death. Two novel compounds, Aurkine 16 18, were designed evaluated for their antitumor effects in both naïve cisplatin-resistant CCA cells, cancer-associated fibroblasts (CAFs), healthy cholangiocytes, vivo models. Aurkines effectively induced leading to increased damage elevated levels reactive oxygen species, resulting greater cytotoxicity than cisplatin cells. Phosphoproteomic molecular analysis revealed activates pathways, while primarily induce apoptosis. Importantly, also triggered apoptosis cells CAFs without harming cholangiocytes. Additionally, demonstrated other cancers, such as breast ovarian cancer. This tumor selectivity results from reduced uptake, efflux, compact chromatin structure normal limiting Aurkine-DNA interactions. In vivo, inhibited growth subcutaneous tumors, well orthotopic tumors immunocompetent mice immune recruitment, any adverse events. Transport studies selectively taken up by OCT1, OCT3, CTR1, OATP1A2, whereas only CTR1 transported cisplatin. represent promising drugs cancers due properties selective targeting malignant study introduces strategy frequent breaks evident toxic side at doses. approach may settle basis strategies overcome critical challenge drug resistance treatment, has potential be breakthrough not treatment biliary but cancers.

Language: Английский

Citations

0
Efficacy and biomarker analysis of second‐line nab‐paclitaxel plus sintilimab in patients with advanced biliary tract cancer DOI Creative Commons

Xiaofen Li,

Nan Zhou, Yang Yu

et al.

Cancer Science, Journal Year: 2024, Volume and Issue: 115(7), P. 2371 - 2383

Published: April 18, 2024

Abstract Biliary tract cancer (BTC) is a highly aggressive malignancy with limited second‐line therapy. We conducted this phase 2 trial to evaluate the efficacy and safety of nab‐paclitaxel plus sintilimab in advanced BTC. Histologically confirmed BTC patients documented disease progression after first‐line chemotherapy were enrolled. Subjects received 125 mg/m on days 1 8 200 mg day 1, administered every 3 weeks. The primary end point was objective response rate (ORR). secondary points progression‐free survival (PFS), overall (OS), adverse reactions. Simultaneously, next‐generation sequencing, programmed cell death ligand immunohistochemistry multiplex immunofluorescence tumor‐infiltrating lymphocytes applied explore potential biomarkers. Twenty‐six subjects consecutively ORR 26.9% (7/26), including two complete responses five partial responses, which met point. control 61.5% (16/26). median PFS 169 (about 5.6 months, 95% confidence interval [CI] 60–278 days). OS 442 14.7 CI 298–586 Grade treatment‐related events (TRAEs) mainly anemia (27%), leukopenia (23%), neutropenia (19%), peripheral sensory neuropathy (8%). No grade 4 or 5 TRAEs occurred. Biomarker analysis suggested that positive PD‐L1 high proportions CD8 + T‐cell infiltration correlated improved clinical outcome. Nab‐paclitaxel potentially effective tolerable regimen for deserves be studied large‐scale trials. status T might promising biomarkers prediction.

Language: Английский

Citations

2
Cellular Senescence in Liver Cancer: How Dying Cells Become “Zombie” Enemies DOI Creative Commons
Aurora Gazzillo, Camilla Volponi, Cristiana Soldani

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 12(1), P. 26 - 26

Published: Dec. 21, 2023

Liver cancer represents the fourth leading cause of cancer-associated death worldwide. The heterogeneity its tumor microenvironment (TME) is a major contributing factor metastasis, relapse, and drug resistance. Regrettably, late diagnosis makes most liver patients ineligible for surgery, frequent failure non-surgical therapeutic options orientates clinical research to investigation new drugs. In this context, cellular senescence has been recently shown play pivotal role in progression chronic inflammatory diseases, ultimately cancer. Moreover, stem-like state triggered by associated with emergence drug-resistant, aggressive clones. recent years, an increasing number studies have emerged investigate senescence-associated hepatocarcinogenesis derived therapies, promising results. review, we intend provide overview evidence that unveils forms primary metastatic cancer, focusing on involvement mechanism therapy

Language: Английский

Citations

6
Extrahepatic Cholangiocarcinoma: Genomic Variables Associated With Anatomic Location and Outcome DOI
William Preston, Esther Drill, Thomas Boerner

et al.

JCO Precision Oncology, Journal Year: 2024, Volume and Issue: 8

Published: July 1, 2024

PURPOSE This study aimed to define genomic differences between perihilar cholangiocarcinoma (PCA) and distal (DCA) identify determinants of survival. MATERIALS AND METHODS Consecutive patients with ECA tissue for targeted next-generation sequencing were analyzed, stratified by anatomic site (PCA/DCA), disease extent, treatment. Associations alterations, clinicopathologic features, outcomes analyzed using Cox proportional hazards regression compare RESULTS In total, 224 diagnosed 2004 2022 (n = 127 PCA; n 97 DCA) met inclusion criteria. The median survival was 29 months (43 after resection 17 from diagnosis unresectable disease). Compared PCA, DCA enriched in TP53alt (alterations; 69% v 33%; Q < 0.01), epigenetic pathway alterations (45% 29%; 0.041), had more total altered pathways (median 3 2; 0.01). KRASalt frequency similar PCA (36%) (37%); however, KRAS G12D (19% 9%; P .002). No other or variables distinguished subtypes. resected patients, no associated outcome. However, CDKN2Aalt (hazard ratio [HR], 2.59 [1.48 4.52]) APCalt (HR, 5.11 [1.96 13.3]) reduced For the entire cohort, irresectability 3.13 [2.25 4.36]), 1.80 [1.80 2.68]), 2.00 [1.04 3.87]) poor CONCLUSION ECA, primarily advanced disease. As genetically similar, coanalysis future studies is reasonable.

Language: Английский

Citations

2