The Role of AKT in Soft Tissue Sarcoma: Review and Insights

Abstract

Soft tissue sarcomas (STS) are a biologically diverse group of mesenchymal tumors that predominantly exhibit a poor prognosis. Surgical resection is considered the mainstay of treatment and provides the only chance for long-term survival. However, some patients present with locally advanced, unresectable disease, and for those who are able to undergo resection, tumor recurrence occurs in over half of patients. In addition, the efficacy of conventional systemic therapies remains dismal. The serine/threonine kinase AKT pathway is one of the most frequently aberrant activated signaling pathways that has been verified in many types of human cancer. Dysregulation of the AKT cascade is known to result in tumorigenesis and aggressive clinical behavior for many tumor types including STS. Epidermal growth factor receptor (EGFR), with its downstream effectors, phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT)/mammalian target of rapamycin (mTOR), have been investigated for decades as promising targets for the treatment of STS, but significant challenges remain and the prognosis of patients with advanced STS has not improved in over two decades. In this review, we will first describe the AKT pathway and its role in STS tumor biology and then discuss the current challenges in targeting the AKT pathway to treat patients with advanced sarcoma.