Oncogenic mutation-driven metabolism-immunity regulatory axis: Potential prospects for thyroid cancer precision therapy

Oncogenes enhance cancer development, and their specific activating mutations exemplify the mechanisms that initiate and mediate thyroid cancer (TC) progression. Research has predominantly focused on how oncogenes promote the development of different TC subtypes by influencing the downstream signaling pathways. Targeted therapies show significant efficacy; however, they often induce drug resistance through feedback activation or compensatory signaling bypasses. Recent evidence indicates that thyroid oncogenes initiate and mediate TC progression, and contribute to drug resistance in distinct TC subtypes through induced metabolic reprogramming and immune microenvironment remodeling. Hence, we propose the concept “Oncogene-Metabolism-Immunity axis.” We discussed the molecular mechanisms by which oncogene-driven metabolic reprogramming and tumor immune microenvironment Remodeling (TIME), and their mutual interactions, induce TC progression, drug resistance, and immune evasion. Finally, we systematically evaluated and summarized potential strategies targeting key oncogenes, metabolic catalysts, immune checkpoints (ICs), and combination therapies to enhance the efficacy of targeted treatments for TC and overcome drug resistance.