The HER3 pathway as a potential target for inhibition in patients with biliary tract cancers.

Abstract

INTRODUCTION:

Expression of human epidermal growth factor receptor (HER)2 and HER3 have been investigated in small BTC studies using variable scoring systems.

METHODS:

HER2 and HER3 overexpression/amplification were explored following internationally agreed guidelines using immunohistochemistry (IHC) and fluorescent in-situ hybridisation (FISH), respectively. Logistic regression and survival analysis (Kaplan Meier, Log rank test and Cox Regression) were used for statistical analysis.

RESULTS:

Sixty-seven eligible patients with Stage I/II (31.3%) or III/IV (68.7%) disease at diagnosis were included. Membrane HER2 overexpression/amplification was identified in 1 patient (1%). HER3 overexpression was predominantly cytoplasmic; the rate of overexpression/amplification of HER3 in membrane and cytoplasm was 16% [ampullary cancer (AMP) (1/13; 8%), gallbladder cancer (GBC) (1/10; 10%), intra-hepatic cholangiocarcinoma (ICC) (6/26; 23%), extra-hepatic cholangiocarcinoma (ECC) (3/18; 17%)] and 24% [AMP (1/13; 8%), GBC (1/10; 10%), ICC (10/26; 38%), ECC (4/18; 22%)], respectively.

CONCLUSIONS:

A significant subset of patients with BTC expressed HER3. Inhibition of HER3 warrants further investigation. A better understanding of the downstream effects of HER3 in BTC requires further mechanistic investigations to identify new biomarkers and improve patient selection for future clinical trials.

• Authors: Angela Lamarca, Salvatore Galdy, Jorge Barriuso, Sharzad Moghadam, Elizabeth Beckett, Jane Rogan, Alison Backen, Catherine Billington, Mairéad G McNamara, Richard A Hubner, Angela Cramer, Juan W Valle
• Journal: PloS one (PLoS One) Vol. 13 Issue 10 Pg. e0206007 ( 2018) ISSN: 1932-6203 [Electronic] United States
• PMID: 30335866 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ERBB2 protein, human
• Receptor, ErbB-2
• Receptor, ErbB-3

Topics

• Aged
• Biliary Tract Neoplasms (drug therapy)
• Computer Simulation
• Female
• Genome, Human
• Humans
• Male
• Middle Aged
• Molecular Targeted Therapy
• Multivariate Analysis
• Proportional Hazards Models
• Receptor, ErbB-2 (metabolism)
• Receptor, ErbB-3 (antagonists & inhibitors, metabolism)
• Signal Transduction
• Survival Analysis