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      Is Open Access

      Consensus Molecular Subtypes (CMS) in Metastatic Colorectal Cancer - Personalized Medicine Decision

      research-article
      , M.D., Ph.D., * , 1 , 2
      Radiology and Oncology
      Sciendo
      metastatic colorectal cancer, heterogeneity, biomarkers, consensus molecular subtypes, CMS1, CMS2, CMS3, CMS4

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          Abstract

          Background

          Colorectal cancer (CRC) is one of the most common types of cancer in the world. Metastatic disease is still incurable in most of these patients, but the survival rate has improved by treatment with novel systemic chemotherapy and targeted therapy in combination with surgery. New knowledge of its complex heterogeneity in terms of genetics, epigenetics, transcriptomics and microenvironment, including prognostic and clinical characteristics, led to its classification into various molecular subtypes of metastatic CRC, called consensus molecular subtypes (CMS). The CMS classification thus enables the medical oncologists to adjust the treatment from case to case. They can determine which type of systemic chemotherapy or targeted therapy is best suited to a specific patient, what dosages are needed and in what order.

          Conclusions

          CMS in metastatic CRC are the new tool to include the knowledge of molecular factors, tumour stroma and signalling pathways for personalized, patient-orientated systemic treatment in precision medicine.

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          Most cited references16

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          Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer

          In this Review, Dienstmann et al. analyse the complex nature of colorectal cancer and the different subtypes in which this disease can be classified, advocating for a 'multi-molecular' perspective for the development of therapies to treat it.
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            Treatment sequencing in metastatic colorectal cancer

            Metastatic colorectal cancer (mCRC) remains incurable in most cases, but survival has improved with advances in cytotoxic chemotherapy and targeted agents. However, the optimal use and sequencing of these agents across multiple lines of treatment is unclear. Here, we review current treatment approaches and optimal treatment sequencing across the first-, second- and third-line settings in mCRC, including biological aspects affecting sequencing and rechallenge. Effective first-line therapy is a key determinant of treatment outcomes and should be selected after considering both clinical factors and biological markers, notably RAS and BRAF. The second-line regimen choice depends on the systemic therapies given in first-line. Anti-angiogenic agents (e.g. bevacizumab, ramucirumab and aflibercept) are indicated for most patients, whereas epidermal growth factor receptor (EGFR) inhibitors do not improve survival in the second-line setting. Molecular profiling is important in third-line treatment, with options in RAS wild-type patients including EGFR inhibitors (cetuximab or panitumumab), regorafenib and trifluridine/tipiracil. Immunotherapy with pembrolizumab or nivolumab ± ipilimumab may be considered for patients with high microsatellite instability disease. Targeting HER2/neu amplification shows promise for the subset of CRC tumours displaying this abnormality. Sequencing decisions are complicated by the potential for any treatment break or de-escalation to evoke a distinct clinical progression type. Ongoing trials are investigating the optimal sequencing and timing of therapies for mCRC. Molecular profiling has established new targets, and increasing knowledge of tumour evolution under drug pressure will possibly impact on sequencing.
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              Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance)

              To determine the predictive and prognostic value of the consensus molecular subtypes (CMSs) of colorectal cancer (CRC) that represent a merging of gene expression-based features largely in primary tumors from six independent classification systems and provide a framework for capturing the intrinsic heterogeneity of CRC in patients enrolled in CALGB/SWOG 80405.
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                Author and article information

                Journal
                Radiol Oncol
                Radiol Oncol
                raon
                raon
                Radiology and Oncology
                Sciendo
                1318-2099
                1581-3207
                September 2020
                28 May 2020
                : 54
                : 3
                : 272-277
                Affiliations
                [1 ]Department of Medical Oncology, Institute of Oncology Ljubljana , Ljubljana, Slovenia
                [2 ]Faculty of Medicine, University of Ljubljana , Ljubljana, Slovenia
                Author notes
                [* ] Assist. Prof. Martina Reberšek, M.D., Ph.D., Department of Medical Oncology, Institute of Oncology Ljubljana, Zaloška 2, SI-1000 Ljubljana, Slovenia. mrebersek@ 123456onko-i.si
                Article
                raon-2020-0031
                10.2478/raon-2020-0031
                7409603
                32463385
                47f4c0d4-4a31-45f6-9e42-5e3b929fe9c8
                © 2020 Martina Rebersek, published by Sciendo

                This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

                History
                : 13 March 2020
                : 29 April 2020
                Page count
                Pages: 6
                Categories
                Review

                Oncology & Radiotherapy
                metastatic colorectal cancer,heterogeneity,biomarkers,consensus molecular subtypes,cms1,cms2,cms3,cms4

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