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. 2026 Jan 13;16:1726210. doi: 10.3389/fimmu.2025.1726210

Figure 3.

Flowchart outlining a tumor treatment process. It starts with the initial diagnosis, assessing pathological classification, drug resistance, and detection methods. Biomarkers for ferroptosis sensitivity are then detected, including molecular, metabolic, and immune markers. Patients are stratified into sensitive and non-sensitive groups. The sensitive group undergoes ferroptosis inducer and immunotherapy, while the non-sensitive group engages in preprocessing and follow-up treatment. Efficacy and safety are assessed, with treatment adjustment options based on effectiveness and toxicity. Safety monitoring involves hematology, cardiotoxicity, and iron overload measures.

Clinical workflow for ferroptosis-targeted therapy in drug-resistant cancer: from initial diagnosis to treatment adjustment. Step 1 (Initial Tumor Diagnosis): Clarify cancer pathological classification and assess prior treatment history to determine drug-resistant status. Step 2 (Ferroptosis Sensitivity Biomarker Detection): Analyze three types of markers—molecular markers (ACSL4, GPX4, SLC7A11, TfR1), metabolic markers (PUFA-PL content, LIP levels), and immune markers (CD8+ T cell infiltration, PD-L1 expression)—using methods including pathological biopsy and imaging. Step 3 (Patient Stratification): Classify patients into the sensitive group (≥2 ferroptosis-sensitive markers + positive CD8+ T cell infiltration) or non-sensitive group (fewer than 2 sensitive markers or negative CD8+ T cell infiltration). Step 4 (Treatment Planning): Sensitive group receives ferroptosis inducers combined with immunotherapy (PD-1 inhibitors restore CD8+ T cell function, enhancing IFNγ-mediated ferroptosis); non-sensitive group undergoes preprocessing with epigenetic regulators (re-detect biomarkers post-preprocessing to switch to sensitive group if eligible). Step 5 (Delivery System & Safety Monitoring): Select nanocarriers for targeted drug delivery; monitor hematology (liver/kidney function), cardiotoxicity (myocardial enzymes), and iron overload (serum ferritin <1000 ng/mL). Step 6 (Efficacy Assessment & Adjustment): Continue the original plan if effective (CR/PR) and safe (recheck every 2 cycles); re-test biomarkers if ineffective (SD/PD); stop treatment and administer iron chelators for excessive toxicity (resume with 50% dose reduction after toxicity alleviation).