title: BRAF in metastatic colorectal cancer: the future starts now.
abstract: BRAF mutations are detectable in about 5-15% of metastatic colorectal cancer (mCRC) patients and represent a clear negative prognostic factor. While in BRAF-mutated (BRAFmt) metastatic melanoma TKI target therapies (BRAF and MEK inhibitor), both alone or in combination, have shown significant efficacy, in BRAFmt CRC single-agent BRAF-inhibitors as well as chemotherapy seem to be ineffective. The critical role of EGFR in CRC and its multiple downstreaming pathways seem to be involved in this lack of response. In recent years, preclinical investigations and retrospective studies slowly increased our knowledge on BRAFmt CRC. This review analyses preclinical data and discusses several clinical trials in order to explore new therapeutic strategies targeting BRAFmt mCRC.
authors.affiliation: Medical Oncology Department, Università Cattolica del Sacro Cuore, Rome, Italy.|Medical Oncology, Sacro Cuore Don Calabria Hospital, Negrar - Verona, Italy.|Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Orlandi
authors.affiliation: Medical Oncology Department, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Calegari
authors.affiliation: Medical Oncology, Sacro Cuore Don Calabria Hospital, Negrar-Verona Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Inno
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Berenato
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Caporale
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Niger
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bossi
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bartolomeo
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; colorectal cancer; immunotherapy; target therapy