PTEN in osteosarcoma: Recent advances and the therapeutic potential

Osteosarcoma is the most common primary malignant bone tumor, predominantly occurring in children and adolescents. Despite treated with surgery and neoadjuvant chemotherapy, osteosarcoma has a high potential of local recurrence and lung metastasis. Overall survival rates for osteosarcoma have plateaued in the past four decades, therefore, identification of novel targets and development of more effective treatment strategies are urgent. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene that negatively regulates the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway. Over half of clinical osteosarcoma samples presented loss or low expression of PTEN, which usually indicated an advanced stage of tumor and a poor prognosis. The expression of PTEN is regulated by epigenetic silence, transcription regulation, post-translational modifications, and protein interactions in osteosarcoma. Therefore, explicating regulations to restore the anti-tumor function of PTEN might provide novel targeted therapies for osteosarcoma. Preclinical evidence suggested directly targeting the altered PTEN in osteosarcoma was promising. Current clinical application of PTEN related therapies in osteosarcoma are PI3K/mTOR inhibitors, and these drugs have shown the favorable efficacy in patients with advanced osteosarcoma.