VEGFA and melanoma: 40 Gong et al. reported high expression of VEGF in the hypoxic core of the spheroid. 21 Qin et al. reported higher expression of VEGF in A375 melanoma spheroids compared to the cells cultured in 2D due to the metabolic variation in spheroidal cells responsible for the sensitivity of cancer cells towards vemurafenib. 41 Moreover, HIF-1α governs the fate of anti-apoptotic proteins such as Bak, Bax, Bcl‐xL, Bcl‐2, Bid, Mcl‐1 NF‐κB, and p53 in 3D spheroid. The hypoxic environment of 3D spheroid further induces drug resistance among the tumor cells. 42