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The Tumor Microenvironment in Colorectal Cancer Therapy

1
Department of Medical Oncology, Hospital Clinic of Barcelona, 08036 Barcelona, Spain
2
Translational Genomics and Targeted Therapeutics in Solid Tumors Group, Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
3
Department of Medicine, University of Barcelona, 08036 Barcelona, Spain
4
Networking Center for Biomedical Research in Hepatic and Digestive Diseases (CIBER-EHD), Instituto de Salud Carlos III, 28029 Madrid, Spain
5
Laboratory of Cell Signaling and Cancer, Institute for Molecular Biology, Science Research Council (CSIC), 08036 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(8), 1172; https://doi.org/10.3390/cancers11081172
Received: 12 July 2019 / Revised: 26 July 2019 / Accepted: 9 August 2019 / Published: 14 August 2019
(This article belongs to the Collection Drug Resistance and Novel Therapies in Cancers)
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Abstract

The current standard-of-care for metastatic colorectal cancer (mCRC) includes chemotherapy and anti-angiogenic or anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, even though the addition of anti-angiogenic agents to backbone chemotherapy provides little benefit for overall survival. Since the approval of anti-angiogenic monoclonal antibodies bevacizumab and aflibercept, for the management of mCRC over a decade ago, extensive efforts have been devoted to discovering predictive factors of the anti-angiogenic response, unsuccessfully. Recent evidence has suggested a potential correlation between angiogenesis and immune phenotypes associated with colorectal cancer. Here, we review evidence of interactions between tumor angiogenesis, the immune microenvironment, and metabolic reprogramming. More specifically, we will highlight such interactions as inferred from our novel immune-metabolic (IM) signature, which groups mCRC into three distinct clusters, namely inflamed-stromal-dependent (IM Cluster 1), inflamed-non stromal-dependent (IM Cluster 2), and non-inflamed or cold (IM Cluster 3), and discuss the merits of the IM classification as a guide to new immune-metabolic combinatorial therapeutic strategies in mCRC. View Full-Text
Keywords: colorectal cancer; mCRC; tumor microenvironment (TME); tumor-infiltrating lymphocytes (TILs); angiogenesis; tumor metabolism colorectal cancer; mCRC; tumor microenvironment (TME); tumor-infiltrating lymphocytes (TILs); angiogenesis; tumor metabolism
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Pedrosa, L.; Esposito, F.; Thomson, T.M.; Maurel, J. The Tumor Microenvironment in Colorectal Cancer Therapy. Cancers 2019, 11, 1172.

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