PTGS2 and neoplasm: Furthermore, tumor-associated macrophages (TAMs) contribute to the development of a pro-tumorigenic microenvironment that fosters resistance to MAPKi therapy by providing an abundance of oxygen, nutrients (resulting in hypoxia and metabolic stress), and extracellular matrix proteins.466 Subsequently, TAMs secrete angiotensin, COX-2, IFN, and IL-1, further promoting the growth and metastasis of melanoma.467 Thus, to enhance the effectiveness of combination therapy for melanoma patients, targeting spatiotemporal interactions within tumor microenvironments holds significant promise.