Abstract

The overall goal of this proposal is to determine if molecular markers found in pretreatment biopsy specimens can predict pathologic complete response (pathCR) in patients with esophageal cancer (EC) undergoing preoperative chemoradiation (CTRT). PathCR is defined as no residual carcinoma in a resected specimen. Patients with EC have a 5-year survival rate of <20%. Localized carcinoma (stage II or III) is frequently treated with preoperative CTRT, but this empirical approach results in heterogeneous and often unpredictable outcomes. Approximately 25% of patients achieve a pathCR and tend to survive longer than do the 75% who achieve The Specific Aims of the proposal are 1. Determine the gene expression profile of the new cohort of 120 patients with esophageal cancer treated with preoperative chemoradiation. 2: Construct statistical models that have a high positive predictive value for pathCR by the gene expression profile of 120 patients. The modeling will include: (a) Identification of subtypes of esophageal cancer by gene expression profiles that are highly homogeneous;(b) Build pathCR prediction models based on specific to subtypes of esophageal cancer as defined in 2(a) and also in the homogeneously treated subgroups. Our attempts to individualize patient's therapy based on molecular biology can pave the way to allow administration of effective therapy, improve safety, and preserve the esophagus in some patients.

Public Health Relevance

This proposal is an early attempt to individualize therapy based on molecular biology for patients with esophageal cancer. Our goal is to pave the way for a strategy in the future that will allow administration of effective therapy, improve safety, and preserve the esophagus in some patients.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA127672-02
Application #
7674679
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Thurin, Magdalena
Project Start
2008-08-15
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2011-07-31
Support Year
2
Fiscal Year
2009
Total Cost
$138,600
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Internal Medicine/Medicine
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Harada, Kazuto; Pool Pizzi, Melissa; Baba, Hideo et al. (2018) Cancer stem cells in esophageal cancer and response to therapy. Cancer 124:3962-3964
Harada, Kazuto; Song, Shumei; Ajani, Jaffer A (2018) Attenuation of YAP1 can potentially target cancer stem cells to overcome drug resistance. Oncoscience 5:214-215
Mizrak Kaya, Dilsa; Nogueras-González, Graciela M; Harada, Kazuto et al. (2018) Risk of peritoneal metastases in patients who had negative peritoneal staging and received therapy for localized gastric adenocarcinoma. J Surg Oncol 117:678-684
Harada, Kazuto; Mizrak Kaya, Dilsa; Baba, Hideo et al. (2018) Immune checkpoint blockade therapy for esophageal squamous cell carcinoma. J Thorac Dis 10:699-702
Harada, Kazuto; Wang, Xuemei; Shimodaira, Yusuke et al. (2018) Early Metabolic Change after Induction Chemotherapy Predicts Histologic Response and Prognosis in Patients with Esophageal Cancer: Secondary Analysis of a Randomized Trial. Target Oncol 13:99-106
Amlashi, Fatemeh G; Wang, Xuemei; Davila, Raquel E et al. (2018) Barrett's Esophagus after Bimodality Therapy in Patients with Esophageal Adenocarcinoma. Oncology 95:81-90
Song, Shumei; Xie, Min; Scott, Ailing W et al. (2018) A Novel YAP1 Inhibitor Targets CSC-Enriched Radiation-Resistant Cells and Exerts Strong Antitumor Activity in Esophageal Adenocarcinoma. Mol Cancer Ther 17:443-454
Sohn, Bo Hwa; Hwang, Jun-Eul; Jang, Hee-Jin et al. (2017) Clinical Significance of Four Molecular Subtypes of Gastric Cancer Identified by The Cancer Genome Atlas Project. Clin Cancer Res :
Lee, Keun-Wook; Lee, Sung Sook; Hwang, Jun-Eul et al. (2016) Development and Validation of a Six-Gene Recurrence Risk Score Assay for Gastric Cancer. Clin Cancer Res 22:6228-6235
Charalampakis, Nikolaos; Nogueras González, Graciela M; Elimova, Elena et al. (2016) The Proportion of Signet Ring Cell Component in Patients with Localized Gastric Adenocarcinoma Correlates with the Degree of Response to Pre-Operative Chemoradiation. Oncology 90:239-47

Showing the most recent 10 out of 31 publications