The lung maintains a delicate balance of response to oxidative stress and protection against tumourigenesis. One of the most critical stress response pathways mammalian cells utilise is controlled by the transcription factor Nuclear factor erythroid-2-related factor 2 (NRF2), which is negatively regulated by the E3 Ubiquitin ligase Kelch-like ECH-associated protein 1 (KEAP1). Alterations in the KEAP1-NRF2 pathway have been identified in 23% of lung adenocarcinomas (ADC) and 34% of squamous cell carcinomas (SCC), though validation of the KEAP1-NRF2 pathway as a driver in lung cancer has not been determined. Using genetically engineered mouse models (GEMMs), we conditionally deleted Keap1 (Keap1f/f) in the lung, utilising inhalation of Adenovirus-driven Cre and investigated the effects on lung cancer development. We found that, while loss of Keap1 alone displayed no abnormalities in the lung, Keap1 loss in combination with oncogenic KrasG12D or loss of Pten promoted malignant transformation. Interestingly, loss of p53, a bona fide lung cancer tumour suppressor gene failed to promote tumour formation, highlighting tumour-promoting selectivity in co-occurring mutations. Given that genetic inactivation of both KEAP1 and PTEN have been identified in lung ADC, we generated Keap1f/f/Ptenf/f mice, and monitored lung tumour initiation and progression in the distal lung, and metabolite profile changes in the serum. Prominently, the Pentose Phosphate Pathway enzymes were altered in these lung tumours, metabolites of which could be identified in the serum of tumour-bearing mice. This highlights the potential of biomarker identification of lung tumours with a highly activated KEAP1-NRF2 pathway.