A55
A systems approach reveals a practical, non-toxic and inexpensive method to resolve the tumour microenvironment and potentially turn malignant tumours benign
Gary Robert Smith
Open University, Milton Keynes, UK
The purpose of this submission is to highlight the importance of the systems approach and the untapped potential for Angiotensin Receptor Blockade in the treatment of all solid tumours.
Classically associated with cardiovascular health, the Angiotensin system is now coming under closer scrutiny and research investigation across diverse disease areas such as Cancer, Neurological disorders, Autoimmune disease and infections. A growing body of knowledge emphasises an emerging pivotal role for Angiotensin in the wound response process, with excessive expression and activation of AT1 (the main receptor for Angiotensin II), leading to prolonged wound recovery and chronic inflammatory conditions.
It is now established that expression of AT1 is a systemic response mechanism in all cell types to stress conditions (Oxidative, Hypoxic and Physical) and activation of the AT1 receptor results in the cellular expression of a full spectrum of chronic inflammatory mediators including TNF-a, IL1b, TGF-b, IL-6, VEGF, Selectins, Integrins, COX-2, RANTES, NAPDH oxidase etc in response to this stress.
Lessons learnt from a systems analysis of the behaviour of Angiotensin in Cancer explains that the induced ‘Wound that never heals’ promotes an environment that is of vital importance in suppressing the adaptive immune response and that Cancers and other infections utilise chronic inflammation in order to spread and evade learned immune responses. Experience, clinical and laboratory evidence demonstrates that solid tumours and other infections (such as MRSA) remain benign if they cannot stimulate or take advantage of wounding.
Angiotensin Receptor blockers (ARBs) have an exceedingly good safety profile, with side effects comparable with placebo even at supramaximal dosage.
ARBs could be used alone, turning malignant tumours into a much more benign form, however the potential for ARBs would be synergistic with all other forms of conventional and developing therapies, greatly improving their effectiveness (especially immune therapies such as cancer vaccines).
