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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Progress in Understanding the IL-6/STAT3 Pathway in Colorectal Cancer

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          Abstract

          As a pleiotropic cytokine, interleukin-6 (IL-6) not only regulates the cellular immune response, but it also promotes tumor development by activating multiple carcinogenic pathways. IL-6 expression is significantly elevated in colorectal cancer (CRC) and is closely related to CRC development and patient prognosis. In CRC, IL-6 activates signal transducers and activators of transduction-3 (STAT3) to promote tumor initiation and tumor growth. IL-6/STAT3 signalling has a profound effect on tumor-infiltrating immune cells in the tumor immune microenvironment in CRC. Additionally, IL-6/STAT3 pathway activates downstream target genes to protect tumor cells from apoptosis; drive tumor cell proliferation, cell cycle progression, invasion and metastasis; promote tumor angiogenesis; and stimulate drug resistance. Therefore, a thorough understanding of the many effects of the IL-6/STAT3 pathway in CRC is needed, which the present review examines.

          Most cited references89

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)
          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Comprehensive Molecular Characterization of Human Colon and Rectal Cancer

            Nikolaus Schultz (2014)
            Summary To characterize somatic alterations in colorectal carcinoma (CRC), we conducted genome-scale analysis of 276 samples, analyzing exome sequence, DNA copy number, promoter methylation, mRNA and microRNA expression. A subset (97) underwent low-depth-of-coverage whole-genome sequencing. 16% of CRC have hypermutation, three quarters of which have the expected high microsatellite instability (MSI), usually with hypermethylation and MLH1 silencing, but one quarter has somatic mismatch repair gene mutations. Excluding hypermutated cancers, colon and rectum cancers have remarkably similar patterns of genomic alteration. Twenty-four genes are significantly mutated. In addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9, and FAM123B/WTX. Recurrent copy number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive CRC and important role for MYC-directed transcriptional activation and repression.
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              Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies

              NaNa Keum, Edward Luciano Giovannucci (2019)
              Globally, colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer death. Arising through three major pathways, including adenoma-carcinoma sequence, serrated pathway and inflammatory pathway, CRC represents an aetiologically heterogeneous disease according to subtyping by tumour anatomical location or global molecular alterations. Genetic factors such as germline MLH1 and APC mutations have an aetiologic role, predisposing individuals to CRC. Yet, the majority of CRC is sporadic and largely attributable to the constellation of modifiable environmental risk factors characterizing westernization (for example, obesity, physical inactivity, poor diets, alcohol drinking and smoking). As such, the burden of CRC is shifting towards low-income and middle-income countries as they become westernized. Furthermore, the rising incidence of CRC at younger ages (before age 50 years) is an emerging trend. This Review provides a comprehensive summary of CRC epidemiology, with emphasis on modifiable lifestyle and nutritional factors, chemoprevention and screening. Overall, the optimal reduction of CRC incidence and mortality will require concerted efforts to reduce modifiable risk factors, to leverage chemoprevention research and to promote population-wide and targeted screening.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): ott
                Journal ID (pmc): ott
                Title: OncoTargets and therapy
                Publisher: Dove
                ISSN (Electronic): 1178-6930
                Publication date (Electronic): 21 December 2020
                Publication date Collection: 2020
                Volume: 13
                Pages: 13023-13032
                Affiliations
                [1 ]Department of Medical Oncology, Guangxi Medical University Cancer Hospital , Nanning, Guangxi 530021, People’s Republic of China
                [2 ]Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital , Nanning, Guangxi 530021, People’s Republic of China
                Author notes
                Correspondence: Rong Liang Department of Medical Oncology, Guangxi Medical University Cancer Hospital , Nanning, Guangxi530021, People’s Republic of ChinaTel +86 771 5333058 Email ronglianggx@126.com
                Author information
                http://orcid.org/0000-0001-5209-9426
                Article
                Publisher ID: 278013
                DOI: 10.2147/OTT.S278013
                PMC ID: 7762435
                PubMed ID: 33376351
                SO-VID: cd6f3beb-7de3-444b-a0b5-18584f36b3c4
                Copyright © © 2020 Lin et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 20 August 2020
                Date accepted : 01 December 2020
                Page count
                Figures: 1, Tables: 2, References: 89, Pages: 10
                Funding
                Funded by: National Natural Science Foundation of China, open-funder-registry 10.13039/501100001809;
                Funded by: China Postdoctoral Science Foundation, open-funder-registry 10.13039/501100002858;
                Funded by: Guangxi Key Research and Development Plan;
                Funded by: Project of the Guangxi Natural Science Foundation;
                Funded by: Guangxi Medical and Health Appropriate Technology Development and Application Project;
                This research was supported by the National Natural Science Foundation of China (NO. 82060427,81660498 and 81803007), China Postdoctoral Science Foundation (NO.2019M663412), Guangxi Key Research and Development Plan (NO.GUIKEAB19245002), Guangxi Scholarship Fund of Guangxi Education Department, General Program of Guangxi Natural Science Foundation (NO. 2020GXNSFAA259080), Youth Talent Fund Project of Guangxi Natural Science Foundation (NO. 2018GXNSFBA281030, 2018GXNSFBA281091), Guangxi Medical and Health Appropriate Technology Development and Application Project (No. S2017101, S2018062), Guangxi Medical University Training Program for Distinguished Young Scholars, Science and Technology Plan Project of Qingxiu District, Nanning (NO.2020037, 2020038).
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: il-6/stat3 pathway,colorectal cancer,tumor development
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: il-6/stat3 pathway, colorectal cancer, tumor development

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