International Journal of Molecular Sciences Review Heterogeneity of Colorectal Cancer Progression: Molecular Gas and Brakes Federica Gaiani 1,2 , Federica Marchesi 3,4, Francesca Negri 5 , Luana Greco 6, Alberto Malesci 3,7, Gian Luigi de’Angelis 1,2 and Luigi Laghi 1,6,* 1 Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy;
[email protected] (F.G.);
[email protected] (G.L.d.) 2 Gastroenterology and Endoscopy Unit, University-Hospital of Parma, via Gramsci 14, 43126 Parma, Italy 3 IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Italy;
[email protected] (F.M.);
[email protected] (A.M.) 4 Department of Medical Biotechnology and Translational Medicine, University of Milan, 20132 Milan, Italy 5 Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy;
[email protected] 6 Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Italy;
[email protected] 7 Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy * Correspondence:
[email protected] Abstract: The review begins with molecular genetics, which hit the field unveiling the involvement of oncogenes and tumor suppressor genes in the pathogenesis of colorectal cancer (CRC) and uncovering genetic predispositions. Then the notion of molecular phenotypes with different clinical behaviors was introduced and translated in the clinical arena, paving the way to next-generation sequencing that captured previously unrecognized heterogeneity. Among other molecular regulators of CRC progression, the extent of host immune response within the tumor micro-environment has a critical Citation: Gaiani, F.; Marchesi, F.; position.