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Although substantial progress has been made in defining the genetic, epigenetic, and molecular drivers of this heterogeneous disease, metabolic reprogramming has only recently emerged as a major determinant of tumour progression and therapeutic response. Cumulative evidence demonstrates that rather than relying on a single nutrient source or pathway, cancer cells integrate glucose and glutamine, fatty acid and one-carbon metabolism, as well as nucleotide biosynthesis, and redox-supporting circuits in a highly context-dependent manner. These programs vary across histological and molecular subtypes, reflecting the influence of lineage identity and oncogenic state on metabolic organisation. In both non-small cell lung cancer and small cell lung cancer, subtype-specific constraints shape distinct metabolic states, yet a common feature is the ability to rapidly shift between alternative nutrients and biosynthetic routes. This adaptability supports continued growth under nutrient limitation, maintains redox homeostasis, and contributes to resistance against conventional and targeted therapies. By summarising current mechanistic evidence, this review presents lung cancer metabolism as an integrated and adaptable system rather than a collection of isolated pathways, and identifies metabolic dependencies that may be leveraged for therapeutic intervention.<\/jats:p>","DOI":"10.1007\/s00018-026-06417-5","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T03:34:02Z","timestamp":1792380842000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lung cancer metabolism: a dynamic and adaptive network"],"prefix":"10.1007","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8457-2564","authenticated-orcid":false,"given":"Sara","family":"Gholamhosseinian-Najjar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3293-7397","authenticated-orcid":false,"given":"Christian","family":"Frezza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"issue":"3","key":"6417_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I et al (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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