Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer

Gut, Journal Year: 2017, Volume and Issue: 67(1), P. 179 - 193

Published: Dec. 12, 2017

Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes.

Language: Английский

---

Underlying Causes and Therapeutic Targeting of the Inflammatory Tumor Microenvironment

Frontiers in Cell and Developmental Biology, Journal Year: 2018, Volume and Issue: 6

Published: June 12, 2018

Historically, the link between chronic inflammation and cancer has long been speculated. Only more recently, pre-clinical epidemiologic data as well clinical evidence all point to role of tumor microenvironment inextricably connected neoplastic process. The (TME), a complex mix vasculature, inflammatory cells, stromal cells is essential "soil" helping modulate potential. Increasingly, suggests that modifies microenvironment, via host mechanisms, including production cytokines, pro-inflammatory mediators, angiogenesis, tissue remodeling. Inflammation can be triggered by variety different pressures, such carcinogen exposure, immune dysfunction, dietary habits obesity, genetic alterations leading oncogene activation or loss suppressors. In this review, we examine concept related both extrinsic intrinsic stimuli promote in turn tumorigenesis. Understanding common pathways inherent an response may shed light on new therapies for primary metastatic disease. personalized medicine pushed field oncology drill down changes cancer, hopes identifying individually targeted agents. Given complexities it clear effective oncologic will necessitate targeting not only but their dynamic relationship well.

Language: Английский

---

The WNT/β‐catenin dependent transcription: A tissue‐specific business

WIREs Mechanisms of Disease, Journal Year: 2020, Volume and Issue: 13(3)

Published: Oct. 21, 2020

Abstract β‐catenin‐mediated Wnt signaling is an ancient cell‐communication pathway in which β‐catenin drives the expression of certain genes as a consequence trigger given by extracellular WNT molecules. The events occurring from signal to transcription are evolutionarily conserved, and their final output orchestrates countless processes during embryonic development tissue homeostasis. Importantly, dysfunctional Wnt/β‐catenin causes developmental malformations, its aberrant activation root several types cancer. A rich literature describes multitude nuclear players that cooperate with generate transcriptional program. However, unified theory how target gene still missing. We will discuss two interactors: factors allow localize at regions on DNA, co‐factors ultimately activate expression. In contrast presumed universality β‐catenin's action, ensemble available evidence suggests view complex system responses different cells tissues. malleable armamentarium might interact order right “canonical” targets each tissue, stage, or disease context. Discovering mechanism tissue‐specific response executed be crucial comprehend seemingly universal fosters wide spectrum Perhaps more importantly, this could inform us about tumor‐specific components need targeted dampen activity oncogenic β‐catenin. This article categorized under: Cancer > Molecular Cellular Physiology Genetics/Genomics/Epigenetics Stem Cells Development

Language: Английский

---

High‐fat diet‐induced dysbiosis mediates MCP‐1/CCR2 axis‐dependent M2 macrophage polarization and promotes intestinal adenoma‐adenocarcinoma sequence

Journal of Cellular and Molecular Medicine, Journal Year: 2020, Volume and Issue: 24(4), P. 2648 - 2662

Published: Jan. 19, 2020

Abstract High‐fat diet (HFD) is a well‐known risk factor for gut microbiota dysbiosis and colorectal cancer (CRC). However, evidence relating HFD, carcinogenesis limited. Our study aimed to demonstrate that HFD‐induced promoted intestinal adenoma‐adenocarcinoma sequence. In clinical study, we found HFD increased the incidence of advanced neoplasia (AN). The expression monocyte chemoattractant protein 1 (MCP‐1), CC chemokine receptor 2 (CCR2) CD163 in CRC patients with was significantly higher than normal diet. When it comes Apc min/+ mice, consumption could induce promote carcinogenesis, accompanying activation MCP‐1/CCR2 axis recruited polarized M2 tumour‐associated macrophages. Interestingly, transfer faecal from HFD‐fed mice another batch absence also enhance without significant body weight gain induced activation. be transmitted. Meanwhile, antibiotics cocktail treatment sufficient inhibit indicating vital role development. Conclusively, these data indicated accelerated sequence through axis, which would provide new insight into better understanding mechanisms prevention HFD‐related CRC.

Language: Английский

---

Driver mutations of the adenoma-carcinoma sequence govern the intestinal epithelial global translational capacity

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(41), P. 25560 - 25570

Published: Sept. 28, 2020

Significance Deregulated global mRNA translation is a feature of various cancers and considered important in oncogenic transformation. In colorectal cancer (CRC), the role most common driver mutations APC , KRAS SMAD4 TP53 on translational capacity are incompletely understood. Here, using mouse human intestinal organoids, we found that each mutation governs epithelial cell. Global linked to known hallmarks, including cell proliferation growth upon accumulation these mutations, posing apparatus as potential therapeutic target CRC.

Language: Английский

---