Format

Send to

Choose Destination
BMC Gastroenterol. 2018 Jun 22;18(1):94. doi: 10.1186/s12876-018-0823-x.

Metabolomic and BH3 profiling of esophageal cancers: novel assessment methods for precision therapy.

Author information

1
Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10; 4-3952, 10 Center Drive, MSC 1201, Bethesda, MD, 20892-1201, USA. Taylor.Ripley@nih.gov.
2
Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10; 4-3952, 10 Center Drive, MSC 1201, Bethesda, MD, 20892-1201, USA.
3
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
4
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
5
Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

Abstract

BACKGROUND:

Esophageal cancers accounted for nearly 16,000 deaths in 2016. The number of patients with esophageal cancers increases every year. Neoadjuvant chemoradiotherapy (nCRT) prior to esophagectomy is a standard treatment for esophageal cancers. The patients who have no residual tumor (pathological complete response (pCR)) at surgery are the most likely to experience long term survival. Accurately determining which patients will have a pCR will improve prognostic information for patients and families, confirm lack of response to nCRT, or avoid surgery if no residual tumor is present. Imaging, endoscopy, and liquid biomarkers have all failed to detect pCR without performing an esophagectomy.

METHODS:

In this study, we are enrolling patients with esophageal adenocarcinoma and squamous cell carcinoma. Patients will undergo standard evaluation including CT scans, laboratory tests, endoscopy with biopsies, and evaluation by a thoracic surgeon. Tissue biopsy is required for enrollment that will be sent for BH3 profiling and metabolomics. Patients will be treated with standard nCRT followed by surgery. Patients with metastatic disease are not eligible. Surgery at the National Cancer Institute will be minimally-invasive robotic surgery. Patients will remain on study indefinitely with regular clinic visits and imaging tests.

DISCUSSION:

The mitochondria are critically involved in the intrinsic pathway apoptosis. Bcl-2 homology domain 3 (BH3) profiling is a technique to measure a cell's susceptibility to apoptosis. BH3 profiling measures the relative interactions of proteins that induce or block apoptosis. The collective balance of these proteins determines whether a cell is near the threshold to undergo apoptosis. If the cell is near this threshold, then the tumor may be more likely to die when treated with nCRT. The mitochondria secrete metabolites that may be detectable as biomarkers. Metabolomics is a global assessment of all metabolite changes that has been performed for detection, monitoring, prognosis, and treatment response in cancers. Stratification of patients based on whether pCR occurs or not may elucidate metabolomic signatures that may be associated with response. We are asking whether BH3 profiling or a metabolomic signature will correlate with tumor death after nCRT for esophageal cancer.

TRIAL REGISTRATION:

NCT03223662 ; Clinicaltrials.gov. July 21, 2017.

KEYWORDS:

BH3 profiling; Esophageal adenocarcinoma; Esophageal squamous cell carcinoma; Metabolomics; Pathologic complete response

PMID:
29933761
PMCID:
PMC6013848
DOI:
10.1186/s12876-018-0823-x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center