Targeting aggressive subtypes of non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer to be diagnosed and is responsible for a high mortality rate. It is characterised by the de-regulation of the PI3K/AKT/mTOR pathway, resulting in the promotion of growth and proliferation of tumour cells. The poor prognosis of NSCLC coupled with the adverse effects elicited by standard cancer treatment reveals the need for more effective and less toxic alternative treatments. In this study, a PI3K/ inhibitor, AZD8835, was investigated for its potential sensitisation effect on large cell carcinoma (LCC), an aggressive subtype of NSCLC. H460 cells were cultured and treated with a range of AZD8835 concentrations. Cell viability was assessed with a PrestoBlue assay at 24, 48, and 72 hour time-points post-drug treatment. Results showed that sensitisation was successfully achieved, with an AZD8835 drug concentration of 0.5M being of particular interest owing to its effect on H460 cell viability which was approximately constant across all three time-points. Furthermore, a possible link between free eIF4E levels and cell viability is also revealed. The use of AZD8835 as part of combination therapy is also briefly discussed in relation to the broader Lung Cancer Enhanced Novel Therapy (LCENT) project where a higher efficacy and the use of a lower drug dosage would ultimately benefit the patient. Although more investigations need to be conducted to assess the effectiveness of AZD8835, especially in other NSCLC subtypes, this drug has potential for future use in NSCLC treatment particularly in combination with other drugs working on common targets.