RLX (PD 139530) is a PI3K/Akt/FoxO3a signaling inhibitor, possessing significant therapeutic potential in experimental colon cancer. RLX can effectively modulate the tumor microenvironment, enhancing the efficacy of cancer immunotherapy. RLX demonstrates the ability to improve the retention time of therapeutic agents within the tumor microenvironment by utilizing advanced nanoparticle delivery systems. RLX can be integrated with various treatment modalities, such as chemotherapy and radiotherapy, to enhance overall tumor therapy effectiveness. RLX highlights the necessity for further research into the tumor microenvironment’s dynamics to develop more tailored treatment approaches for diverse tumor types.