Natural Kinase Inhibitors for the Treatment and Management of Endometrial/Uterine Cancer: Preclinical to Clinical Studies

Endometrial cancer (EC) is the sixth most prevalent type of cancer among women. Kinases, enzymes mediating the transfer of adenosine triphosphate (ATP) in several signaling pathways, play a significant role in carcinogenesis and cancer cells' survival and proliferation. Cyclin-dependent kinases (CDKs) are involved in EC pathogenesis; therefore, CDK inhibitors (CDKin) have a noteworthy therapeutic potential in this type of cancer, particularly in EC type 1. Natural compounds have been used for decades in the treatment of cancer serving as a source of anticancer bioactive molecules. Many phenolic and non-phenolic natural compounds covering flavonoids, stilbenoids, coumarins, biphenyl compounds, alkaloids, glycosides, terpenes, and terpenoids have shown moderate to high effectiveness against CDKin-mediated carcinogenic signaling pathways (PI3K, ERK1/2, Akt, ATM, mTOR, TP53). Pharmaceutical regimens based on two natural compounds, trabectedin and ixabepilone, have been investigated in humans showing short and midterm efficacy as second-line treatments in phase II clinical trials. The purpose of this review is twofold: the authors first provide an overview of the involvement of kinases and kinase inhibitors in the pathogenesis and treatment of EC and then discuss the existing evidence about natural products' derived kinase inhibitors in the management of the disease and outline relevant future research.

Automated summary

Endometrial cancer is a common type of cancer among women, and kinases play a significant role in its development. Cyclin-dependent kinases are believed to be involved in the pathogenesis of endometrial cancer. Natural compounds containing certain substances have shown potential as anticancer agents for the treatment of endometrial cancer. Clinical trials have demonstrated the efficacy of two natural compounds as second-line treatments for this type of cancer.