Resistance is reverted by simultaneous inhibition of EGFR, HER2, and HER3, thereby revealing a potential therapeutic strategy to overcome trastuzumab resistance in patients with gastric cancer.
In this study, we evaluated prevalence of Her3 in gastric cancer, in a Saudi cohort of cases, along with its association with prognostic markers p53 and Ki-67.
We evaluated the expression levels of various ERBB receptor ligands (i.e., heparin-binding epidermal growth factor-like growth factor [HBEGF], transforming growth factor-α [TGFA], amphiregulin [AREG], epiregulin [EREG], epidermal growth factor [EGF], and betacellulin [BTC]) and 3 ERBB family receptors (i.e., epidermal growth factor receptor [EGFR], human EGFR2 [HER2], and ERBB3) in 313 cases of GC using immunohistochemistry, fluorescence in situ hybridization, and mRNA in situ hybridization.
A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer.
Our findings offer compelling evidence that APIP plays an essential role in ERBB3 signaling as a positive regulator for tumorigenesis, warranting future development of therapeutic strategies for ERBB3-driven gastric cancer.
In conclusion, various molecular transduction patterns: Her2/Her3 and Met/Her3 were verified in human GC, and Her3 could serve as a potential target in GC treatment.
Also, the data suggest that ERBB3 is altered in GC and CRC by various ways, including somatic mutations and increased expression that might play roles in tumorigenesis.
Thus, of the RTKs studied, HER3 was the only RTK identified as an independent prognostic indicator of stage II/III advanced gastric cancer with standard treatment.
Nuclear YB-1 expression was significantly (P = 0.026) associated with HER2 expression, but not with EGFR or HER3, in patients with gastric cancer (n = 111).