Lung cancer is one of the leading causes of cancer-related fatalities. Non-small cell lung cancer is the most common type of lung cancer. EML4- ALK-positive NSCLC is a subtype of NSCLC common in non-smokers which can be treated using the tyrosine kinase inhibitor, Alectinib. However, treatment fails due to emergence of drug resistance mediated by activation of the c-MET pathway mediated by activation from hepatocyte growth factor.
We use an evolutionary game-theoretic framework to understand the emergence of acquired drug resistance in EML4- ALK positive NSCLC. For doing so, we first set up in vitro game assays to unveil the dynamics between sensitive, resistant, and producer cells and image the cultures using the incucyte every 6 hours. Using the confluences from the image analysis, we abstract the population frequencies. We characterise the fitness of these populations using a linear regression between growth rates and frequencies. This helps us obtain the pay-off matrix for each game.
Our results reveal that HGF producing cells are the fittest population and that they extend protection to sensitive. This protection is a linear function of producer frequency until the fitness saturates. Cells with intrinsic resistance do not interact significantly with the other cell types.
Tweaking these pay-offs could potentially reveal new therapeutic regimens for treating the game.