Lung microbiome: an emerging player in lung cancer pathogenesis and progression.

The microbiome of the lungs, although until recently neglected, is now emerging as a potential contributor to chronic lung diseases, including cancer. Preclinical evidence suggests that the microbial burden of the lungs shapes the host immunity mechanisms and affects local antitumor immune responses. Studies of cohorts of patients with lung cancer reveal that different microbiome profiles are detected in patients with lung cancer compared to controls. In addition, an association between differential lung microbiome composition and distinct responses to immunotherapy has been suggested, yet, with limited data. Scarce evidence exists on the role of the lung microbiome in the development of metastases in the lungs. Interestingly, the lung microbiome is not isolated and interacts with the gut microbiome through a dynamic axis. Future research on the involvement of the lung microbiome in lung cancer pathogenesis and potential therapeutic implications is greatly anticipated.

BRAF/MEK inhibition in NSCLC: mechanisms of resistance and how to overcome it.

Targeted therapy for oncogenic genetic alterations has changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC). Mutations in the BRAF gene are detected in approximately 4% of patients and result in hyper-activation of the MAPK pathway, leading to uncontrolled cellular proliferation. Inhibition of BRAF and its downstream effector MEK constitutes a therapeutic strategy for a subset of patients with NSCLC and is associated with clinical benefit. Unfortunately, the majority of patients will develop disease progression within 1 year. Preclinical and clinical evidence suggests that resistance mechanisms involve the restoration of MAPK signaling which becomes inhibition-independent due to upstream or downstream alterations, and the activation of bypass pathways, such as the PI3/AKT/mTOR pathway. Future research should be directed to deciphering the mechanisms of cancer cells' oncogenic dependence, understanding the tissue-specific mechanisms of BRAF-mutant tumors, and optimizing treatment strategies after progression on BRAF and MEK inhibition.