In overall, besides implicating ERBB2 as an important therapeutic target under neo-adjuvant or adjuvant settings, we present the first evidence that the presence of KRAS mutations may preclude gallbladder cancer patients to respond to anti-EGFR treatment, similar to a clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer.
In this study, we investigated the cytotoxic effects of different combined therapies with trastuzumab and gemcitabine and/or 5-fluorouracil on HER2-negative GBC cell lines in vitro and in vivo.
Mutations in KRAS exon 2 were examined by a highly sensitive, droplet digital PCR platform using surgically resected specimens of PBM-associated (n = 31) and non-associated gallbladder cancers (n = 49).
IDH1/2 mutations appeared more frequently in ICC (23.6%, P = 0.0002) than in GBC (4.0%) or ECC (2.3%), while ERBB2/3 mutations were found only in GBC (20.0%) and ECC (11.4%).
While in IDH1-2/BAP1/PBRM1 group there were 58%, 22%, and 10% of patients with intrahepatic-cholangiocarcinoma (ICC), perihilar-cholangiocarcinoma (PHCC), and gallbladder cancer (GBC), in KRAS/TP53 group there were 42%, 78%, and 90% of patients with ICC, PHCC, and GBC (p = 0.003), respectively.
While in IDH1-2/BAP1/PBRM1 group there were 58%, 22%, and 10% of patients with intrahepatic-cholangiocarcinoma (ICC), perihilar-cholangiocarcinoma (PHCC), and gallbladder cancer (GBC), in KRAS/TP53 group there were 42%, 78%, and 90% of patients with ICC, PHCC, and GBC (p = 0.003), respectively.
Examples include, interest in the HER2/Neu signaling pathway and the recognition that chronic inflammation plays a crucial role in gallbladder cancer pathogenesis.
We assessed HER2 expression in a consecutive series of 211 GBC cases by immunohistochemistry (IHC), paying particular attention to intratumoral heterogeneity.
A let-7 microRNA binding site polymorphism in the KRAS 3'UTR is associated with increased risk and reduced survival for gallbladder cancer in North Indian population.
Because miR-206 directly suppresses expression of ANXA2 and KRAS, which are thought to promote GBC progression, Malat1 binding of miR-206 in GBC tissue and cells has an oncogenic effect.
We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians.
Gender wise stratification revealed susceptibility for recessive models of PDGFB +1135A>C (OR=3.00) and HER2Ile655Val (OR=2.52) polymorphisms among female GBC cases.
HER2/neu blockade is a promising treatment strategy for gallbladder cancer patients with gene amplification and deserves further exploration in a multi-center study.
The purpose of this study was to examine the frequency of TP53 and K-ras mutations in Bolivian patients with GBC and to compare them with our previous data obtained in other high-GBC-prevalence countries, namely Japan, Chile, and Hungary.