Non-small cell lung cancer (NSCLC) is one of the most lethal malignancies accountings for nearly 80% of all lung cancer cases diagnosed and causing over one million deaths annually worldwide. The discovery of molecular alterations including driver mutations and gene fusions has led to innovation of numerous targeted therapies, which certainly provided an edge over the classical chemotherapeutic treatment regimens and improved survival of the patients. Despite all the breakthrough innovations, the five-year survival statistics has not improved the way it was expected, pointing the challenges and limitations of currently approved diagnostic methods and therapies. This review summarizes various innovative therapies, treatment regimens developed over the last two decades for NSCLC treatment and the current challenges and limitations in the NSCLC treatment landscape.

Metal oxides (MeOx) are exponentially being used in a wide range of applications and are the largest class of commercially produced nanomaterials. This presents unprecedented human exposure. Thus, understanding nanoparticle induced cellular stress can greatly help design strategies to combat them. Scores of studies have been carried out to understand the effects of MeOx nanoparticle exposure on human alveolar cells, which are highly susceptible to aerosolized matter. There is a huge redundancy of information generated, also, a lack of a comprehensive conglomeration of this information. We have built here in a sincere summary of the cellular responses reported till date as a direct consequence of MeOx nanoparticle exposure on human alveolar (A549) cells. Detailed accounts of cellular morphology modulation, generation of reactive oxygen species (ROS) and oxidative stress, inflammation and cytokine release, genotoxic and epi-genotoxic insults, toxicological trend, nanoparticle internalization, modes of cell death, protein synthesis, and membrane damage among others are discussed. Finally, to aid predictability of the highly dynamic and multifactorial nature of this toxicity, we have hypothesized models that describe the ensuing mechanisms based on common patterns discovered throughout our literature survey.

Https://doi.org/10.18632/oncotarget.27558 Makhan Kumar, Ansie Martin, Snehal Nirgude, Bibha Chaudhary, Sukanta Mondal, Angshuman Sarkar