HER-2 inhibition in gastric and colorectal cancers: tangible achievements, novel acquisitions and future perspectives

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.

Radiofrequency Ablation and Microwave Ablation in Liver Tumors: An Update

“…In fact, today the median OS frequency for patients with metastatic colorectal cancer is 30 months, more than double that of 20 years ago; the features involved are a closer patient follow‐up to obtain an earlier detection of metastatic disease, efficacy increase of systemic therapies based on patient selection, and an increase in the number of patients undergoing complete surgical resection of metastases . Additionally, the spread of ablative techniques and of chemotherapeutic targeted therapies can be selectively applied with the aim to make the patient eligible for resection. Although surgical resection is still the gold standard for the management of metastatic liver cancer, most patients are not eligible for this procedure because of anatomic limitations, insufficient functional liver reserve, multifocal nature of the disease, extrahepatic metastases, or medical comorbidities .…”

Effective and persistent antitumor activity of HER2-directed CAR-T cells against gastric cancer cells in vitro and xenotransplanted tumors in vivo

“…Components of the HER2 signaling pathway have been used extensively as a key immunotherapy target in therapy against various solid tumors. Although several anti-HER2 drugs, such as trastuzumab, pertuzumab, lapatinib, and TDM-1, have been tested in clinical GC trials, only trastuzumab is currently approved for the first-line treatment of AGC (Fanotto et al, 2016 ). Hence, to enhance treatment efficacy and minimize drug resistance, the HER2-directed CAR approach has been developed and validated in diverse tumor-bearing mouse models, including those of osteosarcoma (Rainusso et al, 2012 ), breast cancer (Sun et al, 2014 ), renal cancer (Schonfeld et al, 2015 ), and glioblastoma (Zhang et al, 2016 ).…”

Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors

“…It contained novel TP53, RNASEL and SMAD4 mutations that scored as high-confidence putative drivers, as well as ERBB2 and GRIN2A low-confidence putative drivers and an EDNRB mutation. ERBB2 (HER2/Neu) is overexpressed or amplified in a significant fraction of GC [ 82 ], particularly cancers with intestinal histology and cancers of the gastro-esophageal junction. In the ToGA trial [ 83 ], the addition of trastuzumab to chemotherapy significantly increased median overall survival compared to chemotherapy alone in HER2-positive GC.…”