Molecular mechanisms in Barrett's metaplasia and its progression.
The dramatic increase in the incidence and poor overall survival rates of esophageal/gastroesophageal junction adenocarcinoma underscore the necessity to discover molecular markers that can be used for risk assessment, early diagnosis, and targeted therapeutic intervention. Barrett's esophagus (BE) is proposed to represent a precursor of esophageal/gastroesophageal junction adenocarcinoma. BE progression to invasive cancer is defined by a metaplasia-dysplasia-carcinoma progression characterized by an increasing accumulation of genetic changes associated with alterations in molecular gatekeepers of cell circuitries and tissue homeostasis. Using a combination of in situ tissue-based and high-throughput analyses, we investigated alterations of cell-cycle regulators and inflammation-associated molecular effectors. Our data suggest a potential synergistic effect of these alterations for the BE progression to cancer, and underscore the potential use of these markers: (1) in molecular panels assessing cancer risk in BE patients; and (2) as potential therapeutic targets for chemopreventive interventions and to enhance response to anti-neoplastic therapies.
Izzo
Julie G
JG
Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. jizzo@mdanderson.org
Luthra
Rajyalakshmi
R
Wu
Tseung-Teh
TT
Correa
Arlene M
AM
Luthra
Madan
M
Anandasabapathy
Sharmila
S
Chao
K S Clifford
KS
Hung
Mien-Chie
MC
Aggarwal
Bharat
B
Hittelman
Walter N
WN
Ajani
Jaffer A
JA
D000230:Adenocarcinoma / Q000473:pathology; D001471:Barrett Esophagus / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D018890:Chemoprevention; D019938:Cyclin D1 / Q000502:physiology; D018450:Disease Progression; D042241:Early Diagnosis; D004938:Esophageal Neoplasms / Q000473:pathology*; D006801:Humans; D008679:Metaplasia; D016328:NF-kappa B / Q000502:physiology; D011230:Precancerous Conditions / Q000473:pathology*; D018570:Risk Assessment; D015398:Signal Transduction / Q000502:physiology; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D016328:NF-kappa B; D019938:Cyclin D1