Dissertation
The influence of signaling networks on the pathogenesis of cancers of the lung
Doctor of Philosophy (Ph.D.), Drexel University
May 2016
DOI:
https://doi.org/10.17918/00008268
Abstract
Lung cancer is the leading cause of cancer related mortality and head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally. Both cancers are still not fully understood on a molecular level and treatment efforts frequently fail to cure patients. Analysis of broad signaling networks can provide new insights and is particularly powerful in combination with annotated patient data. We took advantage of available 'omics' databases to augment the study of Anti-Müllerian Hormone (AMH) and its receptor (AMHR2) - two proteins we identified as expressed and active in lung cancer - and of retinoblastoma 1 (RB1) associated cell cycle regulation. To better understand the importance of RB1 activity in HPV-negative HNSCC, we investigated the prognostic value of inhibitory CDK4/6 phosphorylation of RB1 on threonine 356 (T356) in archival HPV-negative tumor specimens from patients who underwent surgical resection and received adjuvant radiation. pT356RB1 was identified as a potential prognostic biomarker and a potential response predictor for CDK4/6 inhibitors. Regarding AMH and AMHR2, we discovered that 6-8% of non-small cell lung cancers express high levels of AMH or AMHR2. Furthermore, we were able to show that AMH/AMHR2 participate in a TGF-b/BMP signaling network and regulates epithelial-mesenchymal transition (EMT) in lung cancer. EMT is related to cancer cell metastasis and resistant to therapy, two dominant drivers of cancer mortality. In summary, we used publically available databases to augment the study of RB1 and AMH/AMHR2, with the goal to better understand the pathogenesis of cancers of the lung, head and neck.
Metrics
14 File views/ downloads
16 Record Views
Details
- Title
- The influence of signaling networks on the pathogenesis of cancers of the lung
- Creators
- Tim Nico Beck
- Contributors
- Erica Golemis (Advisor) - Drexel University, Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Drexel University
- Other Identifier
- 991021888847004721