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      Therapeutic Targets and Tumor Microenvironment in Colorectal Cancer

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          Abstract

          Colorectal cancer (CRC) is a genetically, anatomically, and transcriptionally heterogeneous disease. The prognosis for a CRC patient depends on the stage of the tumor at diagnosis and widely differs accordingly. The tumor microenvironment (TME) in CRC is an important factor affecting targeted cancer therapy. The TME has a dynamic composition including various cell types, such as cancer-associated fibroblasts, tumor-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, as well as extracellular factors that surround cancer cells and have functional and structural roles under physiological and pathological conditions. Moreover, the TME can limit the efficacy of therapeutic agents through high interstitial pressure, fibrosis, and the degradation of the therapeutic agents by enzymatic activity. For this reason, the TME is a fertile ground for the discovery of new drugs. The aim of this narrative review is to present current knowledge and future perspectives regarding the TME composition based on strategies for patients with CRC.

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          Most cited references137

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          The Hallmarks of Cancer

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            The Consensus Molecular Subtypes of Colorectal Cancer

            Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression–based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, evident metabolic dysregulation; and CMS4 (Mesenchymal, 23%), prominent transforming growth factor β activation, stromal invasion, and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intra-tumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC – with clear biological interpretability – and the basis for future clinical stratification and subtype–based targeted interventions.
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              Tumour-associated macrophages as treatment targets in oncology

              Tumour-associated macrophages (TAMs) are key drivers of tumour-promoting inflammation and cancer progression, and are important determinants of responsiveness to a range of therapies. Herein, the authors summarize the roles of TAMs in cancer, and discuss the potential of TAM-targeted therapeutic strategies to complement and synergize with other anticancer treatments.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                25 May 2021
                June 2021
                : 10
                : 11
                : 2295
                Affiliations
                [1 ] Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; vescio@ 123456unicz.it (G.V.); gilda_depaola@ 123456libero.it (G.D.P.)
                [2 ]Department of Health Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; sammarco@ 123456unicz.it
                Author notes
                [* ]Correspondence: gallog@ 123456unicz.it
                Author information
                https://orcid.org/0000-0003-1066-4671
                https://orcid.org/0000-0003-0470-4729
                Article
                jcm-10-02295
                10.3390/jcm10112295
                8197564
                34070480
                1383d956-b652-4631-9256-6f1743e3ef22
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 09 April 2021
                : 21 May 2021
                Categories
                Review

                tumor microenvironment,colorectal cancer,targeted therapy,angiogenesis,tumor-associated macrophages,regulatory t cells,cancer-associated fibroblasts

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