Recently, cancer has become a leading cause of death worldwide, prompting increased research to understand the pathways involved in cancer development and to identify solutions for its treatment. The PI3K/AKT pathway has garnered significant attention because of its involvement in promoting cell proliferation and inhibiting programmed cell death. The protein phosphatase and tensin homolog on chromosome 10 (PTEN) plays a crucial role in inhibiting this pathway, thereby limiting uncontrolled cell proliferation. gene expression is strictly regulated at the transcriptional, posttranscriptional, and posttranslational levels, and recent research has focused on PTEN due to its reduced levels in cancer cells. This review aims to provide a deep understanding of the PTEN protein from structural and regulatory perspectives, its mutated forms, and its interactions with the occurrence of various malignant tumors to summarize the recent work performed to combat cancers via molecular strategies to enhance PTEN.