title: Challenging chemoresistant metastatic colorectal cancer: therapeutic strategies from the clinic and from the laboratory.
abstract: As survival has improved for patients with metastatic colorectal cancer (mCRC), there is an increasing need for effective and well-tolerated third-line and subsequent-lines of treatment. Despite recent advances with the development of new-targeted therapies in this setting, there remains an unmet need to exploit oncogenic drivers of colorectal cancer and overcome acquired resistance. Potential treatment strategies include revisiting old targets such as human epidermal growth factor receptor 2, RAS, and BRAF and investigating new targets such as c-MET, the PI3 kinase, and Wnt pathways, and also the use of immune-checkpoint inhibitors. Here, we review recent phase III trials exploring approved agents, early trials investigating new drugs for chemorefractory mCRC, and the potential of capturing tumour dynamics during its evolution by liquid biopsy analysis.
authors.affiliation: Department of Hematology and Oncology, Division of Oncology, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy andrea.sartorebianchi@ospedaleniguarda.it.
authors.forename: A
authors.initials: A
authors.lastname: Sartore-Bianchi
authors.affiliation: Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) via Gattamelata 64, Padova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Loupakis
authors.affiliation: Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Argilés
authors.affiliation: Department of Medicine I, Comprehensive Cancer Center and Medical University, Vienna, Austria.
authors.forename: G W
authors.initials: GW
authors.lastname: Prager
mesh_terms: D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D048493:Proto-Oncogene Proteins B-raf; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C482119:BRAF protein, human
keywords: circulating tumour cells; colorectal cancer; ctDNA; liquid biopsy; metastatic; targeted therapies