A systematic review of survival outcomes for HPV/p16 sub-groups of oropharyngeal cancer, AND Drug re-purposing in head and neck cancer cell lines

R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)

Junaid, Mustaffa ; Mehanna, Hisham,Wilson, Jayne,Spruce, Rachel

University:University of Birmingham

Department:Institute of Cancer and Genomic Sciences

关键词: R Medicine;    RC Internal medicine;    RC0254 Neoplasms. Tumors. Oncology (including Cancer);   

Others  :  http://etheses.bham.ac.uk//id/eprint/6792/1/Junaid16MScbyRes.pdf

来源: University of Birmingham eTheses Repository

【 摘 要 】

Personalised cancer management has the potential to improve prognostic modelling and clinical outcomes, and to deliver tailor-made therapies. The aim of this study was, firstly, to conduct a systematic review of survival outcomes using a combination of HPV and p16 status in oropharyngeal cancers (OPC), with a particular focus on the significance of the discordant groups. Secondly, to investigate the drug re-purposing prospects of three drug targets (INH001, INH002, INH003) using HPV negative (SCC040) and HPV positive (VU147) head and neck cancer cell lines. Two independent reviewers performed a systematic review of the literature. In total 1318 OPC cases were identified from the 7 included studies. Pooled analysis found the HPV+/p16+ group with the best prognostic outcomes, followed by the HPV-/p16+ cohort. The worst prognosis outcomes were found with HPV-/p16- followed by HPV+/p16-. The 5-year overall survival rates were 81%, 58%, 32% and 42% respectively. The three drug targets were tested using proliferation, migration, flow cytometry and clonogenic assays. Both INH001 and INH003 significantly reduced proliferation of SCC040 cells at 72 hours compared to untreated control (74% +/-8.9 and 93% +/-0.4 respectively). Only INH003 significantly reduced proliferation of VU147 cells at 72 hours (86% +/-1.7). Similarly both drugs demonstrated a significant reduction in SCC040 cell survival using the clonogenic assay (99.5%+/-0.5 and 83% +/-8.7 respectively). INH003 also exhibited a significant effect on SCC040 cells in the flow cytometry cell cycle analysis. These results demonstrate the hypothetical value of prognostic studies to increase our understanding of cancer pathophysiology and patient outcomes. Furthermore there is promise in drug re-purposing methodology to increase the availability of novel and effective cancer therapies.