Wnt, Notch and Hedgehog Activity in Chemo-Naive Tumors Collected During Staging of Esophageal Cancer Patients

Overview

Cancer results when undifferentiated cells grow in an uncontrolled manner, crowding out normal cells, causing morbidity and ultimately mortality. the cancer stem cell theory suggests that most tumors undergo a process of differentiation through which a relatively rare cancer stem or progenitor cell (CSC) gives rise to more differentiated populations of cells (including transiently amplifying cells) comprising the bulk of the tumor. As a result of this cellular diversity, one or more cells within the tumor are likely to be resistant to therapy. Among cells resistant to a given therapy, only CSCs can repopulate the tumor. A key feature of this resistant subset of CSCs is that they repopulate a tumor resistant to the original intervention. The cellular programs driving the uncontrolled proliferation of many solid tumors result from aberrant activity of Wnt, Shh, and/or Notch signaling pathways in esc. Thus, therapies that down-regulate the activity of these fundamental pathways in CSCs will be effective in the treatment of cancer. The investigator's research program focuses on the elucidation of signaling mechanisms, control of cellular processes and discovery of small molecules that selectively target Wnt, Shh, and Notch signaling pathways that are fundamental to CSCs. Our preliminary results identified a novel Notch associated protein NACK that functions as a transcriptional co-activator of Notch. Moreover, Nack is expressed in human solid tumors and is required for cell survival and tumor growth in notch -dependent tumor cells.

The investigator's aim is to further interrogate the link between Notch and Nack.

Specific Aims:

- Identify and isolate the cancer stem cell populations from primary chemo naive esophageal tumor samples.

- Interrogate the status of the Notch,( the link between Notch and Nack), Wnt and Hedghog pathways in the chemo naive esophageal tumor as well as in specific cell populations, such as the CSC.

- Determine the degree of cross-talk between these pathways and which of these pathways is essential for the self renewal properties and tumorigenic properties of the esc population.

- Identify critical targets for therapeutic intervention in CSC populations.

Full Title of Study: “Interrogation of Wnt, Notch, and Hedgehog Activity in Chemonaive Tumors Collected During the Staging Ultrasound Endoscopies of Patients Diagnosed With Esophageal Cancer”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: November 7, 2018

Interventions

  • Procedure: Tumor Biopsy via Ultrasound Endoscopy
    • The staging ultrasound endoscopy is performed on patients previously diagnosed with esophageal cancer via diagnostic biopsy. The staging ultrasound identifies affected lymph nodes and depth of tumor to the esophageal wall. The tumor sampling is via a biopsy forcep (one pass to obtain 100 cells).

Arms, Groups and Cohorts

  • Patients with Esophageal Cancer
    • Tumor Biopsy via Ultrasound Endoscopy

Clinical Trial Outcome Measures

Primary Measures

  • Percentage of samples with identifiable Notch, Wnt and Hedghog pathways in the chemo naive esophageal tumor as well as in cancer stem cell populations (CSC).
    • Time Frame: 24 months

Participating in This Clinical Trial

Inclusion Criteria

  • Patients diagnosed with an esophageal cancer and scheduled for a standard of care endoscopic ultrasound.
  • Patient must sign a consent to be a participant in this protocol.

Exclusion Criteria

  • Patients not diagnosed with an esophageal cancer.
  • Patients that have undergone a previous staging endoscopic ultrasound.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Miami
  • Provider of Information About this Clinical Study
    • Principal Investigator: Anthony Capobianco, Professor – University of Miami
  • Overall Official(s)
    • Anthony Capobianco, MD, Principal Investigator, University of Miami

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