Synthesis of Anti-Metastatic Agent for Cancer Theraphy

Abstract

Breast cancer is the most common cancer in women worldwide and is the cause of millions of deaths around the world each year. The majority of breast cancer related mortalities are a result of metastatic disease involving the formation of secondary tumours where cancer cells have spread from the primary tumour to sites around the body. Among the most difficult to treat are those which belong to the basal-type, or triple-negative intrinsic molecular class as these lack the three key hormone receptors: oestrogen (ER), progesterone (PGR) and human epithelial receptor 2 (Her2) which are the targets of many of the existing, well-established targeted cancer therapeutics. Although there has been progress towards the discovery of a targeted drug for the treatment of metastatic, advanced breast cancer, to date there still remains limited options.

A current area of research interest in the treatment of metastatic disease has focused on the role in which chronic stress plays in tumour progression and the formation of metastases. Subsequently, a number of laboratory studies have shown that stress hormones play a crucial role in the progression of breast cancer and the formation of secondary tumours. It is now known that the action of stress is mediated through the stimulation of the β2-adrenergic receptor by the neurotransmitter and stress hormone norepinephrine. Furthermore, breast cancers have been found to express elevated levels of the β2-adrenergic receptor, and interestingly, the hard-to-treat basal-type (triple-negative) molecular class of breast cancers have been found to express the highest levels compared to other molecular classes.

Crucially, further studies have shown that the pro-metastatic influence of stress (via stimulation of the β2-adrenergic receptor) can be blocked by β-adrenoceptor antagonists such as Propranolol. Therefore, the retardation and potential inhibition of stress-induced breast cancer metastasis by blockade of the β2-adrenergic receptor is a potentially promising therapeutic target option.