Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/117495
Title: OVERRIDING CISPLATIN RESISTANCE IN LUNG SQUAMOUS CELL CARCINOMA: INSIGHTS FROM COMBINATION WITH HDAC INHIBITOR
Authors: KONG LI REN
Keywords: cisplatin, lung squamous cell carcinoma, reversal of resistance, gain-of-function of mutant p53
Issue Date: 24-Jan-2014
Source: KONG LI REN (2014-01-24). OVERRIDING CISPLATIN RESISTANCE IN LUNG SQUAMOUS CELL CARCINOMA: INSIGHTS FROM COMBINATION WITH HDAC INHIBITOR. ScholarBank@NUS Repository.
Abstract: LUNG CANCER REMAINS A LEADING CAUSE OF CANCER-RELATED MORTALITY. IN RECENT YEARS, GENOMIC ANALYSES OF LUNG ADENOCARCINOMA HAVE YIELDED SIGNIFICANT STRATEGIES AGAINST PATHWAY ACTIVATION TO IMPROVE TREATMENT, BUT THESE EFFORTS HAVE BEEN LESS SUCCESSFUL IN LUNG SQUAMOUS CELL CARCINOMA (SCC). IN THIS STUDY, NEXT GENERATION SEQUENCING TECHNOLOGY CONFIRMED A PAUCITY OF ONCOGENIC DRIVER LESIONS IN LUNG SCC. CELL LINES WITH INHERENT RESISTANCE TO CISPLATIN WERE FIRST IDENTIFIED. DRUG-INDUCED PERTURBATIONS TO GENE AND PROTEIN EXPRESSION WERE BEING COMPARED. ACTIVATION OF MAPK/ERK PATHWAY WAS SHOWN TO CONFER CISPLATIN RESISTANCE, WHILE MEK INHIBITORS AND BELINOSTAT AUGMENTED CISPLATIN SENSITIVITY IN SCC CELLS THROUGH INHIBITION OF MAPK/ERK SIGNALLING. PARALLEL INVESTIGATIONS SHOWED THAT BELINOSTAT POTENTIATED CISPLATIN-INDUCED APOPTOSIS IN SCC CELLS HARBOURING TP53 MUTATION. THIS CELL DEATH MECHANISM WAS DEMONSTRATED TO BE A GAIN-OF-FUNCTION EVENT IN P53 MUTANT CELLS. IN SUMMARY, THIS THESIS PRO
URI: http://scholarbank.nus.edu.sg/handle/10635/117495
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
KONG li ren PhD Thesis (electronic).pdf15.49 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

89
checked on Feb 22, 2018

Download(s)

17
checked on Feb 22, 2018

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.