Besides amino acids metabolism, lipid metabolism, especially polyunsaturated fatty acids (PUFAs) and relevant phospholipid metabolism, which are also key drivers of ferroptosis (Pope and Dixon, 2023), were identified as dysregulated in both primary and acquired trastuzumab resistance of HER2-positive breast cancer (Duan et al., 2024a), demonstrating the possibility that targeting PUFA metabolism to induce ferroptosis might provide novel treatment options for overcoming trastuzumab resistance. This evidence concerns the gene ERBB2 and breast carcinoma.