Impact of physiological aging and redox homeostasis on lung cancer progression

During tumorigenesis, cancer cells must overcome barriers of oxidative stress due to increasing levels of reactive oxygen species (ROS).

Following our initial findings, a plethora of studies have shown that cancer cells frequently hijack pathways that ramp up endogenous antioxidant production through metabolic-rewiring and thus promote cancer progression and metastasis.Cancer is a disease strongly linked to aging.

Current dogma stipulates that increased levels of ROS and oxidative damage of cellular macromolecules is a major hallmark of aging. Despite this, studies on the role of physiological aging on lung cancer progression are virtually non-existent.

Furthermore, whether dietary antioxidants or activation of the endogenous oxidative stress response stimulate tumorigenesis in aged subjects is unknown.

Finally, any link between therapy resistance in aggressive subtypes of lung cancer and effectiveness of targeted precision medicines remain unexplored in aged subjects.

Here we propose a detailed program that will begin to address these questions and should markedly increase our knowledge of how physiological aging impacts lung cancer progression, tumor-infiltrating immune cells and response to anti-cancer therapy.

We envision that this knowledge will serve as a foundation for a field in its infancy and could provide novel approaches for personalized cancer therapies, ultimately improving the outcomes for cancer patients in our ever-aging population.