Targeting sphingosine kinase 1 in cancer

Abstract

Cancer is one of largest killers in the world and defeating it represents one of the most important challenges in Medicine today. For instance, annually, around 1.38 million women are diagnosed worldwide with breast cancer and approximately 0.25 million men worldwide are diagnosed with prostate and testicular cancer. Patients with oestrogen receptor-positive breast cancer receiving adjuvent Tamoxifen for five years have on average a 50% reduction in disease recurrence but only a 28% reduction in their rate of mortality and patients with oestrogen receptor negative breast cancer tend to have earlier disease recurrence and reduced survival times. Regarding prostate cancer, only 33% of men with stage 4 metastatic cancer will survive beyond 5 years after diagnosis. Patients with androgen-independent (also known as castrate-independent) prostate cancer have fewer treatment options and metastatic prostate cancer is deemed incurable with a median survival of 6–9 months after its development. The major problem, in terms of successful treatment of cancer, is the development of chemotherapeutic resistance by the cancer cells which results in unopposed metastasis of the cancer and ultimately death of the patient. Therefore, there is a need to identify the mechanisms responsible for the induction of chemotherapeutic resistance and to develop therapeutics that can circumvent or block this and thereby provide an effective means to killing the cancer cell.