Small-Molecule Inhibitors (SMIs) as an Effective Therapeutic Strategy for Endometrial Cancer

Patients diagnosed with endometrial cancer (EC), the most common gynaecological malignancy in women worldwide, cope with a disease associated with poor prognosis and limited treatment options after first-line therapy when it reaches an advanced or metastatic stage. Lately, small-molecule inhibitors have emerged as an alternative targeted therapy, renewing hope in the fight against this disease. The aim of this review is to shed light into the current state and future prospects of small-molecule inhibitors on EC treatment by summarizing the extensive number of clinical trials that have been performed during the last years, and to provide a comprehensive up-to-date document with the most remarkable results. Despite the great effort researchers are making to improve the molecular characterization of tumours, to unravel the underlying mechanism of EC progression, and to increase the efficacy of targeted therapy, we might say that there is still a long way to pave to efficiently treat EC patients. Endometrial cancer (EC) is the sixth most common cancer in women. A continued number of low-risk EC patients at diagnosis, as well as patients diagnosed with advanced-stage disease, will experience an aggressive disease. Unfortunately, those patients will present recurrence or overt dissemination. Systemic cytotoxic chemotherapy treatment on advanced, recurrent, or metastatic EC patients has shown poor results, with median survival rates of less than one year, and median progression-free survival rates of four months. Therefore, the search for innovative and alternative drugs or the development of combinatorial therapies involving new targeted drugs and standard regimens is imperative. Over the last few decades, some small-molecule inhibitors have been introduced in the clinics for cancer treatment, but only a few have been approved by the Food and Drug Administration (FDA) for EC treatment. In the present review, we present the current state and future prospects of small-molecule inhibitors on EC treatment, both alone and in combination