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Title

Targeting kinase dependencies in thyroid cancer

Project Description

Our goals are to understand the regulation and function of the Src signaling pathway in thyroid cancer to determine the most effective therapeutic strategy.  Given that advanced tumors often harbor multiple genetic lesions that result in the activation of several oncogenic signaling pathways which drive tumor progression, it is likely that molecular-targeted therapies, such as Src inhibitors, will need to be combined for maximal therapeutic efficacy.  Thus, the goals of this project are to define pathways that promote sensitivity versus resistance to Src inhibition.  For these studies, we are using a genome-wide short inhibitory RNA (shRNA) library screen and a small molecule kinase dependency screen to identify genes and pathways that promote survival in the presence of Src inhibitors.  Our goal is to identify rational therapeutic strategies that when targeted in combination with Src, will eliminate thyroid cancer cells.  To further address the specific role of Src in thyroid cancer growth, invasion, and metastasis, we are using an orthotopic thyroid cancer model and a novel metastasis model.  We have already shown that inhibition of Src inhibits tumor growth in an orthotopic model, and metastatic growth in an experimental metastasis model, consistent with our in vitro findings (Chan CM et al 2012).  We are further validating the clinical relevance of Src signaling using a comprehensive thyroid tumor microarray. Ultimately the results from this projects will 1) allow for identification of biomarkers to better predict which tumors will respond to inhibitors of the FAK-Src pathway; 2) develop more specific targeted therapies to block distinct components of this pathway that are deregulated; and 3) develop new approaches for limiting the metastatic spread of disease.

Area of Study

Hematology and Oncology

Populations

 

Method

Animal Models; Cell Biology, Molecular Biology, and Genetics

Disease or Symptom

Cancer

Department

Medicine

Mentor Location

12801 E 17th Ave #7103 RC1 South Rm 7119

Mentor Contact Number

303-724-3179

Mentor Email

rebecca.schweppe@ucdenver.edu

Website

http://www.ucdenver.edu/academics/colleges/medicalschool/departments/Pathology/academicprograms/cancerbiology/Pages/Rebecca-Schweppe.aspx

Mentor Name

Schweppe, Rebecca

Funding Department/Program

Cancer Center; Medicine

Status

Current

Display on public listing?

Yes

Upload Date

8/18/2015 9:08 AM

Attachments

Created at 8/21/2015 7:49 AM by Ross, Randy
Last modified at 8/25/2017 11:00 PM by Macfarlane, Helen