Novel therapeutic targets in soft-tissue sarcomas
Abstract/Contents
- Abstract
- Cancer is a disease that is characterized by uncontrolled cell proliferation and is the second leading cause of death in the industrialized world. Cancers can be broadly classified based on their cell type of origin: carcinomas arise from cells of the epithelium, leukemias and lymphomas arise from the cells of the hematopoietic system, and sarcomas arise from cells of the mesenchyme. Recent advances in the understanding of the biological mechanisms of cancer initiation, growth, and metastasis have led to a number of new therapeutic modalities with cancer-specific modes of action; these new biotherapeutic drugs have led to significant improvements in the clinical management of many tumor types. However, these advances have predominantly been directed towards the treatments of carcinomas, leukemias, and lymphomas. For sarcomas, there exist very few available targeted therapies, and the treatment of these tumors remains a significant unmet medical need. This dissertation concerns the identification and inhibition of novel therapeutic targets in sarcomas. In Chapter One, a brief introduction to the epidemiology, biology, and available treatments for cancer is presented. In Chapter Two, a relatively understudied receptor tyrosine kinase (RTK), ROR2, is shown to be a prognostic biomarker of patient outcome and to play a pro-tumorigenic role in two soft-tissue sarcomas, leiomyosarcoma (LMS) and gastrointestinal stromal tumor (GIST). In Chapter Three, a cell surface protein, CD47, is shown to prevent immune-mediated clearance of LMS tumors by macrophages, and anti-CD47 monoclonal antibody (mAb) drugs are demonstrated to have therapeutic efficacy against LMS tumors in vitro and in vivo. In Chapter Four, a mAb directed towards KIT, an RTK over-expressed and mutated in GIST, is shown to slow tumor growth in vitro and in vivo in GIST tumors that are both sensitive and resistant to treatment with the current standard of care drug, imatinib. In Chapter Five, a computational approach is taken to identify novel drugs for LMS by comparing gene expression profiles of these tumors to those of benign lesions arising from the same cell type; drugs identified by this analysis were then tested in vitro on LMS cells. Chapters Six and Seven contain discussions and concluding remarks on the results presented in earlier chapters. In sum, these results help further the identification and experimental validation of novel therapeutic targets in soft-tissue sarcomas. It is hoped that these studies will add to the scientific understanding of soft-tissue sarcoma biology and will help to enable further scientific and clinical advances to improve the lives of patients suffering from these cancers.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Edris, Badreddin |
|---|---|
| Associated with | Stanford University, Department of Genetics |
| Primary advisor | Rijn, Matt van de |
| Thesis advisor | Rijn, Matt van de |
| Thesis advisor | Ford, James M. (James Matthew) |
| Thesis advisor | Galli, Stephen J |
| Thesis advisor | Sage, Julien |
| Thesis advisor | Stearns, Tim |
| Advisor | Ford, James M. (James Matthew) |
| Advisor | Galli, Stephen J |
| Advisor | Sage, Julien |
| Advisor | Stearns, Tim |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Badreddin Edris. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2012. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2012 by Badreddin Edris
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