Title:Advancing Drug Therapy for Brain Tumours: A Current Review of the Pro-inflammatory Peptide Substance P and its Antagonists as Anti-cancer Agents
Volume: 9
Issue: 2
Author(s): Kimberley Mander, Elizabeth Harford-Wright, Kate M. Lewis and Robert Vink
Affiliation:
Keywords:
Blood-brain barrier, CNS tumours, glioma, metastases, substance P, tight junctions.
Abstract: Evidence for the involvement of the Substance P (SP)/NK1 receptor system in the development and progression
of cancer strongly supports its potential as a therapeutic target in malignancies. Novel strategies for approaching cancer
treatment are urgently required particularly with regard to tumours of the central nervous system (CNS), which are notoriously
difficult to effectively treat and associated with extremely poor prognosis for many patients. This is due, in part,
to the presence of the highly specialised blood-brain barrier, which is known to restrict common treatments such as chemotherapy
and hinder early tumour diagnosis. Additionally, tumours of the CNS are difficult to surgically resect completely,
often contributing to the resurgence of the disease many years later. Interestingly, despite the presence of the
blood-brain barrier, circulating tumour cells are able to gain entry to the brain and form secondary brain tumours; however,
the underlying mechanisms of this process remain unclear. Tachykinins, in particular Substance P, have been implicated
in early blood-brain barrier disruption via neurogenic inflammation in a number of other CNS pathologies. Recent
evidence also suggests that Substance P may play a central role in the development of CNS tumours. It has been well established
that a number of tumour cells express Substance P, NK1 receptors and mRNA for the tachykinin NK1 receptor.
This increase in the Substance P/NK1 receptor system is known to induce proliferation and migration of tumour cells as
well as stimulate angiogenesis, thus contributing to tumour progression. Accordingly, the NK1 receptor antagonist presents
a novel target for anti-cancer therapy for which a number of patents have been filed. This review will examine the
role of Substance P in the development of CNS tumours and its potential application as an anti-cancer agent.
