Oncotarget 69060 www.impactjournals.com/oncotarget www.impactjournals.com/oncotarget/ Oncotarget, Vol. 7, No. 42 HER-2 inhibition in gastric and colorectal cancers: tangible achievements, novel acquisitions and future perspectives Valentina Fanotto 1,* , Elena Ongaro 1,* , Karim Rihawi 2 , Antonio Avallone 3 , Nicola Silvestris 4 , Lorenzo Fornaro 5 , Enrico Vasile 5 , Lorenzo Antonuzzo 6 , Francesco Leone 7 , Gerardo Rosati 8 , Francesco Giuliani 4 , Roberto Bordonaro 9 , Mario Scartozzi 10 , Giovanna De Maglio 11 , Francesca V. Negri 12 , Gianpiero Fasola 1 and Giuseppe Aprile 1 1 Department of Oncology, University and General Hospital, Udine, Italy 2 Department of Oncology, S.Orsola-Malpighi Hospital, Bologna, Italy 3 Gastrointestinal Medical Oncology Unit, National Cancer Institute “Fondazione Giovanni Pascale” - IRCCS, Napoli, Italy 4 Department of Oncology, National CancerInstitute “Giovanni Paolo II” - IRCSS, Bari, Italy 5 Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy 6 Department of Oncology, Careggi Hospital, Firenze, Italy 7 Department of Medical Oncology, University of Torino, Candiolo Cancer Institute-FPO - IRCCS, Torino, Italy 8 Medical Oncology Unit, San Carlo Hospital, Potenza, Italy 9 Department of Oncology, ARNAS Garibaldi, Catania, Italy 10 Department of Oncology, University Hospital, Cagliari, Italy 11 Department of Pathology, University and General Hospital, Udine, Italy 12 Medical Oncology Unit, University Hospital, Parma, Italy * These authors have contributed equally to this work Correspondence to: Giuseppe Aprile, email: aprile.giuseppe@aoud.sanita.fvg.it Keywords: gastric cancer, colorectal cancer, HER2-inhibition, prognosis, predictive factor Received: December 11, 2015 Accepted: June 16, 2016 Published: August 12, 2016 ABSTRACT HER-2 (ErbB-2, c-erbB2 or Her2/neu), a member of the HER-family, is directly involved in the pathogenesis and progression of several human cancers; as such, it is also often considered as a poor prognostic factor. Following the revolutionary impact of anti-HER-2 therapy in breast cancer patients, the role of HER-2 and its blockade has also been extensively evaluated in other tumor types, including gastric and colorectal adenocarcinoma. The aims of this review are to recall the important results achieved with the use of HER-2 inhibitors in both gastric and colorectal cancer, and to discuss on the updates available on the role of HER-2 as prognostic and predictive factor in these malignancies. INTRODUCTION HER-2 (ErbB-2, c-erbB2 or Her2/neu), a member of the HER-family that also includes HER-1 (Epidermal Growth Factor Receptor-EGFR, or ErbB1), HER-3 (ErbB3) and HER-4 (ErbB4), is a proto-oncogene that encodes for a 185-kDa plasma membrane-bound tyrosine kinase receptor, located on the chromosome 17 at q21 [1]. Its stimulation by extracellular signals leads to the activation of downstream pathways such as mitogen- activated protein kinase (MAPK), phosphoinositide- 3-kinase (PI3K), phospholipase C and protein kinase C, inducing signal transduction and transcription [2, 3]. As such, HER-2 gene amplifcation and protein overexpression are involved in the pathogenesis and progression of several human cancers, thus they are often considered as a poor prognostic factor [4-6]. HER-2/ neu overexpression has been reported in many epithelial malignancies including lung, prostate, bladder, pancreatic cancer and osteosarcoma. But it is mainly due to the Review