Comprehensive review of targeted therapy for colorectal cancer

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Март 20, 2020

Abstract Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in world was responsible for nearly 881,000 cancer-related deaths 2018. Surgery chemotherapy have long been first choices patients. However, prognosis of CRC has never satisfying, especially patients with metastatic lesions. Targeted therapy a new optional approach that successfully prolonged overall survival Following successes anti-EGFR (epidermal growth factor receptor) agent cetuximab anti-angiogenesis bevacizumab, agents blocking different critical pathways as well immune checkpoints are emerging at an unprecedented rate. Guidelines worldwide currently updating recommended targeted drugs on basis increasing number high-quality clinical trials. This review provides overview existing CRC-targeted their underlying mechanisms, discussion limitations future trends.

Язык: Английский

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Protein Profiling and Sizing of Extracellular Vesicles from Colorectal Cancer Patients via Flow Cytometry

ACS Nano, Год журнала: 2018, Номер 12(1), С. 671 - 680

Опубликована: Янв. 4, 2018

Extracellular vesicles (EVs) have stimulated considerable scientific and clinical interest, yet protein profiling sizing of individual EVs remains challenging due to their small particle size, low abundance proteins, overall heterogeneity. Building upon a laboratory-built high-sensitivity flow cytometer (HSFCM), we report here rapid approach for quantitative multiparameter analysis single down 40 nm with an rate up 10 000 particles per minute. Statistically robust size distribution was acquired in minutes resolution profile well matched those cryo-TEM measurements. Subpopulations expressing CD9, CD63, and/or CD81 were quantified immunofluorescent staining. When HSFCM used analyze blood samples, significantly elevated level CD147-positive identified colorectal cancer patients compared healthy controls (P < 0.001). provides sensitive platform surface EVs, which could greatly aid the understanding EV-mediated intercellular communication development advanced diagnostic therapeutic strategies.

Язык: Английский

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Genetic and biological hallmarks of colorectal cancer

Genes & Development, Год журнала: 2021, Номер 35(11-12), С. 787 - 820

Опубликована: Июнь 1, 2021

Colorectal cancer has served as a genetic and biological paradigm for the evolution of solid tumors, these insights have illuminated early detection, risk stratification, prevention, treatment principles. Employing hallmarks framework, we provide conceptual framework to understand how alterations in colorectal drive cell biology properties shape heterotypic interactions across cells tumor microenvironment. This review details research advances pertaining genetics cancer, emerging concepts gleaned from immune single-cell profiling, critical remaining knowledge gaps influencing development effective therapies this that remains major public health burden.

Язык: Английский

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FXR Regulates Intestinal Cancer Stem Cell Proliferation

Cell, Год журнала: 2019, Номер 176(5), С. 1098 - 1112.e18

Опубликована: Фев. 1, 2019

Язык: Английский

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Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis

Molecular Cancer, Год журнала: 2020, Номер 19(1)

Опубликована: Июль 27, 2020

Abstract Background Colorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators intercellular communication and that abundant Circular RNAs (circRNAs) are enriched within exosomes. CircRNAs novel members noncoding regulating proliferation progression. However, function regulatory mechanism cancer-derived exosomal circRNAs in CRC remains unclear. Methods cells-derived exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA) western blot. CCK-8, wound healing transwell assays, flow cytometry assays conducted to assess whether would affect proliferation, metastasis, apoptosis cells, respectively. Moreover, we performed RNA sequencing RT-qPCR identify exosome-stimulated cells. Fluorescence situ hybridization (FISH) assay was used detect cellular distribution circPACRGL. Bioinformatic analyses (StarBase 2.0) pool miRNA targets Luciferase verify direct interaction. Finally, differentiation N1-N2 neutrophils. Results Our study identified a CRC-derived circRNA, We found circPACRGL significantly upregulated cells after tumor-derived addition . serves sponge for miR-142-3p/miR-506-3p facilitate transforming growth factor- β1 (TGF-β1) expression. As result, promoted cell migration invasion, well N1 N2 neutrophils via miR-142-3p/miR-506-3p-TGF- axis. Conclusion study, first reveal plays an oncogenic role providing mechanistic insights into roles progression valuable marker treatment.

Язык: Английский

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Determinants and clinical implications of chromosomal instability in cancer

Nature Reviews Clinical Oncology, Год журнала: 2018, Номер 15(3), С. 139 - 150

Опубликована: Янв. 3, 2018

Язык: Английский

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Fusobacterium nucleatum in Colorectal Carcinoma Tissue According to Tumor Location

Clinical and Translational Gastroenterology, Год журнала: 2016, Номер 7(11), С. e200 - e200

Опубликована: Ноя. 1, 2016

Evidence suggests a possible role of Fusobacterium nucleatum in colorectal carcinogenesis, especially right-sided proximal colorectum. Considering change bowel contents and microbiome from to distal segments, we hypothesized that the proportion carcinoma enriched with F. might gradually increase along subsites rectum cecum.A retrospective, cross-sectional analysis was conducted on 1,102 colon rectal carcinomas molecular pathological epidemiology databases Nurses' Health Study Professionals Follow-up Study. We measured amount DNA tumor tissue using quantitative PCR assay equally dichotomized nucleatum-positive cases (high vs. low). used multivariable logistic regression examine relationship subsite variable (rectum, rectosigmoid junction, sigmoid colon, descending splenic flexure, transverse hepatic ascending cecum) nucleatum.The nucleatum-high cancers increased (2.5%; 4/157) cecal (11%; 19/178), statistically significant linear trend all (P<0.0001) little evidence non-linearity. The nucleatum-low higher rectal, than middle segments.The increases cecum. Our data support continuum model reflects pathogenic influences gut microbiota neoplastic immune cells challenges prevailing two-colon (proximal distal) dichotomy paradigm.

Язык: Английский

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Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(19), С. 10260 - 10260

Опубликована: Сен. 23, 2021

Colorectal cancer (CRC) is a predominant malignancy worldwide, being the fourth most common cause of mortality and morbidity. The CRC incidence in adolescents, young adults, adult populations increasing every year. In pathogenesis CRC, various factors are involved including diet, sedentary life, smoking, excessive alcohol consumption, obesity, gut microbiota, diabetes, genetic mutations. tumor microenvironment (TME) involves complex cooperation between tumoral cells with stroma, immune, endothelial cells. Cytokines several growth (GFs) will sustain cell proliferation, survival, motility, invasion. Epidermal factor receptor (EGFR), Insulin-like -1 (IGF-1R), Vascular Endothelial Growth Factor -A (VEGF-A) overexpressed human cancers CRC. phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target rapamycin (mTOR) all three major subfamilies mitogen-activated protein (MAPK) signaling pathways may be activated by GFs further play key roles development. main aim this review to present incidence, risk factors, pathogenesis, impact during its Moreover, article describes relationship EGF, IGF, VEGF, inhibitors, PI3K/AKT/mTOR-MAPK pathways,

Язык: Английский

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Comparison of ⁶⁸Ga-FAPI and ¹⁸F-FDG Uptake in Gastric, Duodenal, and Colorectal Cancers

Radiology, Год журнала: 2020, Номер 298(2), С. 393 - 402

Опубликована: Дек. 1, 2020

Background: Accurate clinical staging is crucial to managing gastrointestinal cancer, but fluorine 18 ( F) fluorodeoxyglucose (FDG) PET/CT has limitations.Targeting fibroblast-activation protein a newer diagnostic approach for the visualization of tumor stroma, and gallium 68 Ga)-labeled inhibitors (FAPIs), hereafter Ga-FAPIs, present promising alternative F-FDG.Purpose: To compare efficacy Ga-FAPI in primary metastatic lesions malignancies with that F-FDG PET/CT. Materials Methods:Images from patients gastric, duodenal, colorectal cancers who underwent contemporaneous between October 2019 through June 2020 were retrospectively analyzed. 18F-FDG uptakes compared by using Wilcoxon signed-rank test.The McNemar test was used performance two techniques.Results: Thirty-five (median age, 64 years [interquartile range, 53-68 years]; men) evaluated.In treatment-naive (n = 19), led upstaging TNM stage four (21%) PET/CT.Tracer uptake higher than (gastric cancer: 12.7 vs 3.7, respectively, P .003;colorectal 15.9 7.9, .03),involved lymph nodes (6.7 2.4, , .001), bone visceral metastases (liver metastases: 9.7 5.2, .001;peritoneal 8.4 3.6, .001;bone 4.3 2.2, .001;lung 4.4 1.9, .01).In addition, sensitivity detection tumors (100% [19 19] 53% [10 19], respectively; .004),lymph (79% [22 28] 54% [15 28], (89% [31 35] 57% [20 35], .001). Conclusion:Gallium inhibitor superior cancers, tracer most lesions.

Язык: Английский

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Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

Cells, Год журнала: 2019, Номер 9(1), С. 60 - 60

Опубликована: Дек. 24, 2019

Heat shock proteins (HSPs) constitute a large family of molecular chaperones classified by their weights, and they include HSP27, HSP40, HSP60, HSP70, HSP90. HSPs function in diverse physiological protective processes to assist maintaining cellular homeostasis. In particular, participate protein folding maturation under stressors such as heat shock, hypoxia, degradation. Notably, also play essential roles across cancers are implicated variety cancer-related activities cell proliferation, metastasis, anti-cancer drug resistance. this review, we comprehensively discuss the functions association with cancer initiation, progression, metastasis therapy Moreover, potential utilization enhance effects chemo-, radio-, immunotherapy is explored. Taken together, have multiple clinical usages biomarkers for diagnosis prognosis well therapeutic targets treatment.

Язык: Английский

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