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For example, in glutamine-addicted clear cell renal cell carcinomas, the competitive consumption of glutamine by tumor cells results in local deprivation of extracellular glutamine, which activates HIF-1 and induces tumor-infiltrating macrophages to secrete IL-23

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Despite the efficacy of mTOR inhibitors in reducing primary tumor growth and CSC activity, lung metastasis remain resistant to treatment, indicating distinct mechanisms driving metastasis compared to primary tumor growth in ER + mammary carcinomas exposed to high collagen density [15]

Therefore, further investigations are needed to assess potential vascular effects of hyperhomocysteinemia-associated changes in the SAM to SAH ratio, which regulates SAM-dependent methyltransferases and hence, methylation reactions