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During tumor initiation, major oncogenic pathways drive early metabolic reprogramming of lipid, amino acid, and energy pathways to promote cell competition and clonal expansion. These metabolic changes reciprocally shape the tumor microenvironment (TME) through metabolite fluxes, extracellular matrix remodeling, and immune reprogramming, generating adaptive niches that sustain tumor progression and metastasis. Cancer cell metabolic adaptability becomes even more crucial to survive dissemination and adapt to a new, distant microenvironment.<\/jats:p>\n                  <jats:p>Here, we discuss these dynamic interplays and highlight the p53 pathway as an integrative hub linking oncogenic signaling, metabolic rewiring, and tumor microenvironmental adaptation throughout carcinogenesis. We will also outline how emerging technologies may redefine the TME\u2010p53\u2010metabolism interplay uncovering therapeutically exploitable metabolic vulnerabilities.<\/jats:p>","DOI":"10.1002\/bies.70175","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:47:07Z","timestamp":1787140027000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Dynamic Alliance of p53 and Metabolism in the Tumor Microenvironment Shapes Tumor Evolution"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5613-2665","authenticated-orcid":false,"given":"Sebastien M.","family":"Joruiz","sequence":"first","affiliation":[{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB) Area Science Park\u2010Padriciano  Trieste 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