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397 In a Phase II trial (NCT02420314) for advanced NSCLC, Ascorbate combined with Carboplatin and Paclitaxel inhibited tumor growth through HO generation, iron modulation (higher transferrin linked to improved PFS), and immune activation (4.2-fold increase in CD8 + T cells), achieving a 34.2% response rate and a 12.8-month median OS

Under normoxic conditions, Nrf2 levels are low, predominantly due to binding to the negative regulator KEAP1 (Kelch-like ECH-associated protein 1), which facilitates Nrf2 ubiquitination and proteasomal degradation [160]