6 Conclusion Persistent barriers in solid tumor therapy, including uneven drug penetration, hypoxia- and acidosis-associated resistance and local immunosuppression, reflect structural and functional imbalances in the TME
This step also initiates the multidisciplinary meeting described in the following section, where all data streams are integrated
Hence, it is likely that NAPQI leads to oxidation of one or more enzymes involved in the conversion of methionine to cysteine, preventing GSH resynthesis from this precursor in phase 2, whereas with NAC such inhibition does not prevent GSH resynthesis.26 Recent studies have provided evidence that cystathionine beta -synthase and cystathionine gamma -lyase, necessary for the conversion of methionine to cysteine, are targets for thiol oxidation by NAPQI.27 Following treatment with NAC, the resulting GSH can act both to detoxify NAPQI by conjugation and to reverse toxicity by thiol reduction
In the future, it will be interesting to explore the therapeutic effect of combining 177 Lu-FAPI with established anti-tumour therapies like immunotherapy and chemotherapy