An overexpression of insulin receptors and insulin-like growth factors lead to the promotion of cell cycle progression and inhibition of apoptosis.51,52 The overexpressed insulin receptors on cancer cells of diabetic patients, who are also characterized by hyperinsulinemia, may be activated, leading to the ability of cancer cells to evade destruction by chemoradiotherapy, resulting in an unfavorable PR and CR.53 As a result, hypoxia and hyperglycemia occur, which might help remodeling the TME into an even more aggressive environment, leading to poorer response to nCRT.54 The gene discussed is INS; the disease is hyperinsulinism.