This paradox arises from RNS’s intricate regulatory networks within the tumor microenvironment (TME), which involve crosstalk with immune cells (e.g., TAMs, TANs), stromal components, and key signaling pathways (e.g., PI3 K/Akt, NF-κB, HIF-1α) throughout tumor initiation, progression, and metastasis. This evidence concerns the gene HIF1A and neoplasm.