In therapeutic strategy development, structure biology-based precision designs (e.g., PROTAC degraders) and combination therapies—such as ST80 enhancing TNBC immunotherapy by disrupting the OTUD4-CD73 complex (201) and crizotinib suppressing NSCLC via targeting the OTUB1/pSTAT3 axis (207)—are overcoming functional redundancy challenges, while the combined use of ERRα inhibitors and metabolic modulators underscores the necessity of multi-target interventions (208). Here, ESRRA is linked to non-small cell lung carcinoma.