Sphingosine kinase 1 in breast cancer.

Breast cancer affects 1 out of 8 women in the US and is the second highest cause of death from cancer for women, leading to considerable research examining the causes, progression, and treatment of breast cancer. Over the last two decades, sphingosine-1-phosphate (S1P), a potent sphingolipid metabolite, has been implicated in many processes important for breast cancer including growth, progression, transformation and metastasis, and is the focus of this review. In particular, one of the kinases that produces S1P, sphingosine kinase 1 (SphK1), has come under increasing scrutiny as it is commonly upregulated in breast cancer cells and has been linked with poorer prognosis and progression, possibly leading to resistance to certain anti-cancer therapies. In this review, we will also discuss preclinical studies of both estrogen receptor (ER) positive as well as triple-negative breast cancer mouse models with inhibitors of SphK1 and other compounds that target the S1P axis and have shown good promise in reducing tumor growth and metastasis. It is hoped that in the future this will lead to development of novel combination approaches for effective treatment of both conventional hormonal therapy-resistant breast cancer and triple-negative breast cancer.