Cell death in pancreatic cancer: from pathogenesis to therapy

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2021, Volume and Issue: 18(11), P. 804 - 823

Published: July 30, 2021

Language: Английский

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Metabolic networks in mutant KRAS-driven tumours: tissue specificities and the microenvironment

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(8), P. 510 - 525

Published: July 9, 2021

Language: Английский

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Microbiota in Tumors: From Understanding to Application

Advanced Science, Journal Year: 2022, Volume and Issue: 9(21)

Published: May 23, 2022

Microbes with complex functions have been found to be a potential component in tumor microenvironments. Due their low biomass and other obstacles, intratumor microbiota is poorly understood. Mucosal sites normal adjacent tissues are important sources of microbiota, while hematogenous spread also leads the invasion microbes. Intratumor affects progression tumors through several mechanisms, such as DNA damage, activation oncogenic pathways, induction immunosuppression, metabolization drugs. Notably, different types tumors, composition abundance highly heterogeneous may play roles tumors. Because concern this field, techniques omics immunological methods used study microbiota. Here, recent progress field reviewed, including related heterogeneity. Techniques that can discussed. Moreover, research summarized into development strategies antitumor treatment prospects for possible future field.

Language: Английский

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Context-Specific Determinants of the Immunosuppressive Tumor Microenvironment in Pancreatic Cancer

Cancer Discovery, Journal Year: 2023, Volume and Issue: 13(2), P. 278 - 297

Published: Jan. 9, 2023

Immunotherapies have shown benefits across a range of human cancers, but not pancreatic ductal adenocarcinoma (PDAC). Recent evidence suggests that the immunosuppressive tumor microenvironment (TME) constitutes an important roadblock to their efficacy. The landscape TME differs substantially PDAC subtypes, indicating context-specific principles immunosuppression. In this review, we discuss how cells, local TME, and systemic host environmental factors drive immunosuppression in context. We argue unraveling mechanistic drivers modes will open new possibilities target more efficiently by using multimodal (immuno)therapeutic interventions. Immunosuppression is almost universal hallmark cancer, although entity highly heterogeneous its different subtypes phenotypes. Here, provide diverse cancer central executor various context-dependent immunosuppression, key challenges novel opportunities uncover, functionalize, functional nodes for therapeutic exploitation.

Language: Английский

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Intratumoural microbiota: a new frontier in cancer development and therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 10, 2024

Abstract Human microorganisms, including bacteria, fungi, and viruses, play key roles in several physiological pathological processes. Some studies discovered that tumour tissues once considered sterile actually host a variety of which have been confirmed to be closely related oncogenesis. The concept intratumoural microbiota was subsequently proposed. Microbiota could colonise through mucosal destruction, adjacent tissue migration, hematogenic invasion affect the biological behaviour tumours as an important part microenvironment. Mechanistic demonstrated potentially promote initiation progression by inducing genomic instability mutations, affecting epigenetic modifications, promoting inflammation response, avoiding immune regulating metabolism, activating metastasis. Since more comprehensive profound insights about intratumoral are continuously emerging, new methods for early diagnosis prognostic assessment cancer patients under examination. In addition, interventions based on show great potential open chapter antitumour therapy, especially immunotherapy, although there some inevitable challenges. Here, we aim provide extensive review concept, development history, sources, heterogeneity, carcinogenic mechanisms explore role microorganisms prognosis, discuss current treatment regimens target research prospects limitations this field.

Language: Английский

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Noncoding RNAs as regulators of STAT3 pathway in gastrointestinal cancers: Roles in cancer progression and therapeutic response

Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 43(5), P. 1263 - 1321

Published: March 23, 2023

Abstract Gastrointestinal (GI) tumors (cancers of the esophagus, gastric, liver, pancreas, colon, and rectum) contribute to a large number deaths worldwide. STAT3 is an oncogenic transcription factor that promotes genes associated with proliferation, antiapoptosis, survival, metastasis. overactivated in many human malignancies including GI which accelerates tumor progression, metastasis, drug resistance. Research recent years demonstrated noncoding RNAs (ncRNAs) play major role regulation signaling pathways pathway. The types endogenous ncRNAs are being extensively studied oncology microRNAs, long RNAs, circular RNAs. These can either be tumor‐promoters or tumor‐suppressors each one them imparts their activity via different mechanisms. pathway also tightly modulated by ncRNAs. In this article, we have elaborated on tumor‐promoting tumors. Subsequently, comprehensively discussed as well suppressor functions mechanism action known modulate cancers.

Language: Английский

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Type I conventional dendritic cells facilitate immunotherapy in pancreatic cancer

Science, Journal Year: 2024, Volume and Issue: 384(6703)

Published: June 27, 2024

Inflammation and tissue damage associated with pancreatitis can precede or occur concurrently pancreatic ductal adenocarcinoma (PDAC). We demonstrate that in PDAC coupled (ptPDAC), antigen-presenting type I conventional dendritic cells (cDC1s) are specifically activated. Immune checkpoint blockade therapy (iCBT) leads to cytotoxic CD8 + T cell activation elimination of ptPDAC restoration life span even upon rechallenge. Using antigen-loaded cDC1s as a vaccine, immunotherapy-resistant was rendered sensitive iCBT tumors. cDC1 vaccination identified specific CDR3 sequences the tumor-infiltrating potential therapeutic importance. This study identifies fundamental difference immune microenvironment concurrent with, without, provides rationale for combining treatment option.

Language: Английский

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Consensus, debate, and prospective on pancreatic cancer treatments

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Oct. 10, 2024

Pancreatic cancer remains one of the most aggressive solid tumors. As a systemic disease, despite improvement multi-modality treatment strategies, prognosis pancreatic was not improved dramatically. For resectable or borderline patients, surgical strategy centered on improving R0 resection rate is consensus; however, role neoadjuvant therapy in patients and optimal chemotherapy with without radiotherapy were debated. Postoperative adjuvant gemcitabine/capecitabine mFOLFIRINOX recommended regardless margin status. Chemotherapy as first-line for advanced metastatic included FOLFIRINOX, gemcitabine/nab-paclitaxel, NALIRIFOX regimens whereas 5-FU plus liposomal irinotecan only standard care second-line therapy. Immunotherapy an innovative although anti-PD-1 antibody currently agent approved by MSI-H, dMMR, TMB-high tumors, which represent very small subset cancers. Combination strategies to increase immunogenicity overcome immunosuppressive tumor microenvironment may sensitize immunotherapy. Targeted therapies represented PARP KRAS inhibitors are also under investigation, showing benefits progression-free survival objective response rate. This review discusses current modalities highlights cancer.

Language: Английский

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Probiotics functionalized with a gallium-polyphenol network modulate the intratumor microbiota and promote anti-tumor immune responses in pancreatic cancer

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 17, 2024

The intratumor microbiome imbalance in pancreatic cancer promotes a tolerogenic immune response and triggers immunotherapy resistance. Here we show that Lactobacillus rhamnosus GG probiotics, outfitted with gallium-polyphenol network (LGG@Ga-poly), bolster by modulating microbiota-immune interactions. Upon oral administration, LGG@Ga-poly targets tumors specifically, selectively eradicates tumor-promoting Proteobacteria microbiota-derived lipopolysaccharides through gallium-facilitated disruption of bacterial iron respiration. This elimination microbiota impedes the activation tumoral Toll-like receptors, thus reducing immunosuppressive PD-L1 interleukin-1β expression tumor cells, diminishing immunotolerant myeloid populations, improving infiltration cytotoxic T lymphocytes tumors. Moreover, hampers growth both preventive therapeutic contexts, amplifies antitumor efficacy checkpoint blockade preclinical models female mice. Overall, offer evidence thoughtfully designed biomaterials targeting can efficaciously augment for challenging cancer.

Language: Английский

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Emerging roles of long noncoding RNAs in chemoresistance of pancreatic cancer

Seminars in Cancer Biology, Journal Year: 2020, Volume and Issue: 83, P. 303 - 318

Published: Nov. 15, 2020

Language: Английский

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