The Promise of Combination Therapies with FOXM1 Inhibitors for Cancer Treatment

Simple Summary FOXM1 is an oncogenic transcription factor that has been implicated in cancer progression, metastases, and chemotherapy resistance. Multiple small-molecule FOXM1 inhibitors have been studied in the lab, but none have made it to clinical trials. The aim of this review is to describe the studied combination therapies with FOXM1 inhibitors. We evaluated the synergistic role of FOXM1 inhibitors with chemotherapy and molecular-targeted therapies for cancer treatment. Small-molecule FOXM1 inhibitors are promising compounds whose therapeutic benefits can be applied to different pediatric and adult cancers.Abstract Forkhead box M1 (FOXM1) is a transcription factor in the forkhead (FOX) family, which is required for cellular proliferation in normal and neoplastic cells. FOXM1 is highly expressed in many different cancers, and its expression is associated with a higher tumor stage and worse patient-related outcomes. Abnormally high expression of FOXM1 in cancers compared to normal tissue makes FOXM1 an attractive target for pharmacological inhibition. FOXM1-inhibiting agents and specific FOXM1-targeted small-molecule inhibitors have been developed in the lab and some of them have shown promising efficacy and safety profiles in mouse models. While the future goal is to translate FOXM1 inhibitors to clinical trials, potential synergistic drug combinations can maximize anti-tumor efficacy while minimizing off-target side effects. Hence, we discuss the rationale and efficacy of all previously studied drug combinations with FOXM1 inhibitors for cancer therapies.