Tumor suppressor genes, such as P53 and retinoblastoma protein (RB), are crucial regulators in cancer progression.125–127 Specifically, P53 acts as a sentinel, responding to intracellular disturbances like metabolic and oxidative stress, and inducing cell cycle arrest until the TME returns to a balanced state.128,129 However, some tumors are able to bypass these suppressor genes or deactivate pivotal tumor suppressors. This evidence concerns the gene RB1 and cancer.