Abstract

Limitations in successfully treating metastasis development remain an obstacle in preventing disease progression in aggressive forms of cancer. Despite an improved understanding about the mechanistic biological pathways of metastasis formation, the ability to translate laboratory findings into therapies for significant patient benefit have been disappointingly slow. In this perspective, we briefly summarise the principal concepts of metastasis development, and the strengths and weaknesses associated with the current clinical approach to its treatment. Moreover, the recent clinical evidence for a new antimetastatic treatment is reviewed concerning the use of adrenergic receptor antagonists (betablockers). The principal aim of this Special Edition is to illustrate that a high science methodology approach has been used in testing the hypothesis that stress can drive disease progression in cancer. Stimulation of adrenergic receptors resulting from stress hormones and mediators released from the sympathetic nervous system have been shown to enhance disease progression in several cancer types. Current levels of understanding based on in vitro studies suggest that this is achieved through direct effects on cancer cells involving pro-migratory stimulation. But more recent in vivo investigations suggest increased complexity involving interaction between the primary tumour and inflammatory cells in its immediate microenvironment. Further studies are needed to better understand the relationship between the sympathetic and inflammatory disease pathways in cancer disease progression. But ahead of this, increasing clinical evidence from epidemiology studies demonstrate that blocking adrenergic receptors in patients with some forms of cancer translates into significant gains in survival, achieved through a reduction in metastasis formation.

Keywords: Adrenergic receptors, adrenoceptors, beta-blockers, metastasis, therapy, cancer