Wnt, Notch and Hedgehog Activity in Chemo-Naive Tumors Collected During Staging of Esophageal Cancer Patients
| Status: | Terminated |
|---|---|
| Conditions: | Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 1/17/2019 |
| Start Date: | April 5, 2013 |
| End Date: | November 7, 2018 |
Interrogation of Wnt, Notch, and Hedgehog Activity in Chemonaive Tumors Collected During the Staging Ultrasound Endoscopies of Patients Diagnosed With Esophageal Cancer
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.
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.
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.
We found this trial at
1
site
Miami, Florida 33124
(305) 284-2211
Principal Investigator: Anthony Capobianco, MD
Phone: 305-243-6308
University of Miami A private research university with more than 15,000 students from around the...
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