Colorectal Cancer: A Review of Carcinogenesis, Global Epidemiology, Current Challenges, Risk Factors, Preventive and Treatment Strategies

Cancers, Journal Year: 2022, Volume and Issue: 14(7), P. 1732 - 1732

Published: March 29, 2022

Colorectal cancer (CRC) is the second most deadly cancer. Global incidence and mortality are likely to be increased in coming decades. Although deaths associated with CRC very high high-income countries, fatalities related growing developing countries too. detected early entirely curable by surgery subsequent medications. However, recurrence rate high, drug resistance increases treatment failure rate. Access diagnosis of for survival somewhat possible developed countries. these facilities rarely available Highlighting current status CRC, its development, risk factors, management crucial creating public awareness. Therefore, this review, we have comprehensively discussed global epidemiology, resistance, challenges, preventive strategies CRC. Additionally, there a brief discussion on development pathways recommendations preventing treating

Language: Английский

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Advances in targeted therapy for esophageal cancer

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Oct. 7, 2020

Abstract Esophageal cancer (EC) is one of the most lethal cancers in world, and its morbidity mortality rates rank among top ten China. Currently, surgical resection, radiotherapy chemotherapy are primary clinical treatments for esophageal cancer. However, outcomes still unsatisfactory due to limited efficacy severe adverse effects conventional treatments. As a new type approach, targeted therapies have been confirmed play an important role treatment cancer; these include cetuximab bevacizumab, which target epidermal growth factor receptor (EGFR) vascular endothelial (VEGF), respectively. In addition, other drugs targeting surface antigens signaling pathways or acting on immune checkpoints continuously developed. For example, trastuzumab, monoclonal antibody human 2 (HER-2), has approved by Food Drug Administration (FDA) as first-line HER-2-positive Moreover, PD-L1 inhibitor pembrolizumab highly efficient drug patients with PD-L1-positive advanced squamous cell carcinoma (ESCC). These novel can be used alone combination strategies further improve prognosis patients. Nevertheless, events, optimal dosages effective combinations need investigation. this review, we expound outline latest advances mechanisms relevant drugs, discuss their safety, provide rationale precision medicine

Language: Английский

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Genetic and biological hallmarks of colorectal cancer

Genes & Development, Journal Year: 2021, Volume and Issue: 35(11-12), P. 787 - 820

Published: June 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.

Language: Английский

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Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial

The Lancet Oncology, Journal Year: 2021, Volume and Issue: 22(6), P. 779 - 789

Published: May 4, 2021

Language: Английский

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Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 388(1), P. 44 - 54

Published: Dec. 21, 2022

Adagrasib, an oral small-molecule inhibitor of mutant KRAS G12C protein, has shown clinical activity in pretreated patients with several tumor types, including colorectal cancer. Preclinical studies suggest that combining a epidermal growth factor receptor antibody could be effective strategy.In this phase 1-2, open-label, nonrandomized trial, we assigned heavily metastatic cancer to receive adagrasib monotherapy (600 mg orally twice daily) or (at the same dose) combination intravenous cetuximab once week (with initial loading dose 400 per square meter body-surface area, followed by 250 meter) every 2 weeks 500 meter). The primary end points were objective response (complete partial response) and safety.As June 16, 2022, total 44 had received adagrasib, 32 therapy cetuximab, median follow-up 20.1 months 17.5 months, respectively. In group (43 evaluable patients), was reported 19% (95% confidence interval [CI], 8 33). duration 4.3 CI, 2.3 8.3), progression-free survival 5.6 4.1 8.3). combination-therapy (28 46% 28 66). 7.6 5.7 not estimable), 6.9 5.4 8.1). percentage grade 3 4 treatment-related adverse events 34% 16% group. No 5 observed.Adagrasib antitumor G12C, both as cetuximab. more than 6 Reversible common two groups. (Funded Mirati Therapeutics; KRYSTAL-1 ClinicalTrials.gov number, NCT03785249.).

Language: Английский

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Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 22(1), P. 130 - 130

Published: Dec. 24, 2020

Colorectal cancer (CRC), the third most common type of cancer, is second leading cause cancer-related mortality rates worldwide. Although modern research was able to shed light on pathogenesis CRC and provide enhanced screening strategies, prevalence still rise. Studies showed several cellular signaling pathways dysregulated in CRC, onset malignant phenotypes. Therefore, analyzing involved metastasis necessary elucidate underlying mechanism progression pharmacotherapy. This review focused target genes as well various including Wnt/β-catenin, p53, TGF-β/SMAD, NF-κB, Notch, VEGF, JAKs/STAT3, which are associated with metastasis. Additionally, alternations methylation patterns relation regulating mechanisms such cell cycle, transcription, apoptosis, angiogenesis invasion were also reviewed. To date, understanding genomic epigenomic instability has identified candidate biomarkers that validated for routine clinical use management. Nevertheless, better can aid development early detection molecular markers risk stratification methods improve care patients.

Language: Английский

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Butyrate producers, “The Sentinel of Gut”: Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 12, 2023

Gut-microbial butyrate is a short-chain fatty acid (SCFA) of significant physiological importance than the other major SCFAs (acetate and propionate). Most producers belong to Clostridium cluster phylum Firmicutes, such as Faecalibacterium , Roseburia Eubacterium Anaerostipes Coprococcus Subdoligranulum Anaerobutyricum . They metabolize carbohydrates via butyryl-CoA: acetate CoA-transferase pathway kinase terminal enzymes produce most butyrate. Although, in minor fractions, amino acids can also be utilized generate glutamate lysine pathways. Butyrogenic microbes play vital role various gut-associated metabolisms. Butyrate used by colonocytes energy, stabilizes hypoxia-inducible factor maintain anaerobic environment gut, maintains gut barrier integrity regulating Claudin-1 synaptopodin expression, limits pro-inflammatory cytokines (IL-6, IL-12), inhibits oncogenic pathways (Akt/ERK, Wnt, TGF-β signaling). Colonic shape microbial community secreting anti-microbial substances, cathelicidins, reuterin, β-defensin-1, homeostasis releasing anti-inflammatory molecules, IgA, vitamin B, molecules. Additionally, producers, anti-carcinogenic metabolites, shikimic precursor conjugated linoleic acid. In this review, we summarized significance butyrate, critically examined relevance contextualized their therapeutics.

Language: Английский

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Metastatic colorectal cancer: mechanisms and emerging therapeutics

Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 44(4), P. 222 - 236

Published: Feb. 23, 2023

Language: Английский

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Biomarkers in Colorectal Cancer: Current Research and Future Prospects

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(15), P. 5311 - 5311

Published: July 27, 2020

Colorectal cancer (CRC) is a leading cause of death worldwide, despite progress made in detection and management through surgery, chemotherapy, radiotherapy, immunotherapy. Novel therapeutic agents have improved survival both the adjuvant advanced disease settings, albeit with an increased risk toxicity cost. However, metastatic continues to poor long-term prognosis significant challenges remain due late stage diagnosis treatment failure. Biomarkers are key tool early detection, prognostication, survival, predicting response. The past three decades seen advances genomics molecular pathology biomarkers, allowing for greater individualization therapy positive impact on outcomes. Clinically useful predictive biomarkers aid clinical decision making, such as presence KRAS gene mutations benefit from epidermal growth factor receptor (EGFR) inhibiting antibodies. few been translated into practice highlighting need further investigation. We review range protein, DNA RNA-based under investigation diagnostic, predictive, prognostic properties CRC. In particular, long non-coding RNAs (lncRNA), investigated cancers including colorectal cancer. Specifically, we evaluate potential role lncRNA plasmacytoma variant translocation 1 (PVT1), oncogene, prognostic, biomarker

Language: Английский

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Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study

The Lancet, Journal Year: 2023, Volume and Issue: 402(10395), P. 41 - 53

Published: June 16, 2023

Language: Английский

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