{
  "abstract": "Colorectal cancer (CRC) is one of the most common malignant cancers and its incidence is steadily rising particularly in young patients. While screening measures and the widespread availability of surgical treatment have led to an impressive improvement of prognosis within the overall CRC population, patients with metastatic CRC still face 5-year survival rates of around 10–25%. Despite continuous development of new systemic treatment strategies that include cytotoxic chemotherapy and targeted therapy, most patients with metastatic CRC eventually progress. However, a small proportion of patients with mismatch repair-deficient or microsatellite unstable CRC responds exceptionally well to treatment with immune checkpoint inhibitors, thereby proving that CRC is in principle amenable to immunotherapy and showing that long-term disease stabilisation can be achieved even in metastasised stages. However, the reasons for the lack of response to immunotherapy in the vast majority of CRC cases remain to be elucidated. Yet, recent evidence suggests that the tumour stroma, which includes non-immune cells in the colorectal tumour microenvironment, mediates immunosuppressive mechanisms that prevent effective immunotherapy. These findings open new avenues for the development of advanced immunotherapies for CRC. In this review, we summarise major developments in the systemic therapy of CRC within the last couple of decades, provide an overview of emerging and soon-to-be implemented therapeutic strategies and present concepts from clinical and preclinical research to manipulate tumour cells and the tumour stroma to sensitise microsatellite stable colorectal tumours to immunotherapy.",
  "authors": [
    {
      "affiliations": [
        "Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt/Main, Germany",
        "Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt/Main, Germany",
        "Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt/Main, Germany"
      ],
      "name": "Christoph Steup"
    },
    {
      "affiliations": [
        "Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt/Main, Germany",
        "Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt/Main, Germany"
      ],
      "name": "Kilian B Kennel"
    },
    {
      "affiliations": [
        "First Department of Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
      ],
      "name": "Markus F Neurath"
    },
    {
      "affiliations": [
        "Department of Surgery, University Medical Center Regensburg, Regensburg, Germany",
        "German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany"
      ],
      "name": "Stefan Fichtner-Feigl"
    },
    {
      "affiliations": [
        "Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt/Main, Germany",
        "Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt/Main, Germany",
        "German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany"
      ],
      "name": "Florian R Greten"
    }
  ],
  "title": "Current and emerging concepts for systemic treatment of metastatic colorectal cancer",
  "uid": "3ea2162f-23d0-57f9-a2e8-0dba9c270666"
}