Synthetic lethal approaches to target cancers with loss of PTEN function

Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene and has a role in inhibiting the oncogenic AKT signaling pathway by dephosphorylating phosphatidylinositol 3,4,5-triphosphate (PIP3) into phosphatidylinositol 4,5-bis phosphate (PIP2). The function of PTEN is regulated by different mechanisms and inactive PTEN results in aggressive tumor phenotype and tumorigenesis. Identifying targeted therapies for inactive tumor suppressor genes such as PTEN has been challenging as it is difficult to restore the tumor suppressor func-tions. Therefore, focusing on the downstream signaling pathways to discover a targeted ther-apy for inactive tumor suppressor genes has highlighted the importance of synthetic lethality studies. This review focused on the potential synthetic lethality genes discovered in PTEN-inactive cancer types. These discovered genes could be potential targeted therapies for PTEN-inactive cancer types and may improve the treatment response rates for aggressive types of cancer.& COPY; 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).