Targeting lipid metabolism in oral cancer.


The survival rates of patients diagnosed with frequently presenting cancer types have improved dramatically in recent years, with the classification of disease based on genetic and molecular constituents opening the door for innovative intervention strategies. However, some cancers have not yet profited from such advances. Survival rates for oral/oropharyngeal squamous cell carcinoma (OSCC/OPSCC) have remained stagnant for the past 50 years, with a 5 year survival rate of 40-50%, dropping to <10% when coupled with metastasis. Conversely, the incidence of OSCC and OPSCC continues to rise, and it is now the 6th most common cancer worldwide (CRUK). Drugs used in treating OSCC/OPSCC remain generic, with poor efficacy and resistance: new, targeted therapeutics are urgently required.
We have utilised a suite of complimentary approaches to identify the most pertinent players in supporting viability and metastasis of OSCC/OPSCC. Interrogation of aggressive cell lines derived from patient tumour tissue (generated in-house and through collaboration) has been undertaken using whole genome siRNA screening under hypoxic and normoxic environmental conditions, coupled with high content phenotypic analysis. This has led to the identification of genes resulting in lethality, a subset of which demonstrates selective lethality under hypoxia. Furthermore, genomic sequencing of our cell lines is ongoing, with the overall aim of identifying genetic signatures associated with identified driver mutations. We are also employing additional data resources (gene expression profiling, pathway mapping, cell line mutation, prognosis/survival etc) to ensure focused target validation of the most apposite genes and pathways. Collectively these approaches will support the development of more target driven, personalised therapeutic options for OSCC/OPSCC patients.

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