The pleiotropic and ubiquitous TGF-Beta signaling has been associated with both normal body physiology and pathophysiology of a number of disease states including cancer. However what still remains incompletely explained is the 'biological cost' or the potential physiological consequences of blocking this necessary evil (TGF-Beta/Smad signaling).
If the physiological consequences of Blocking TGF-Beta can be accurately predicted in terms of its merits and demerits, then the TGF-Beta/Smad can be blocked, since it remains as of now, one of the most singly implicated signaling pathway in cancer. However, if the exact consequences of blocking TGF-Beta signaling cannot be predicted with certainty, then it is better other targets specific to a particular disease state are sought for.
In mice, blocking the pathway has led to huge increases in interferon-gamma expression and subsequent activation of interferon induced pathways
TGF-b1 Knock out mice give some explanation, and uncontrolled inflammatory processes is one of the major issues, agree with comments of Dr. Young. But in adults non smad signaling could be the key point. If TGF beta non Smad signaling is included or not in your question........ The only way to manage TGFbeta pathophysiological role is to develop strategies that inhibit only partial quantitative and qualitative biological activity of this cytokine. Maybe is not the best target but is always in the spotlight.
I recommend you this paper.... maybe could inspire some thoughts.
An integrative modeling framework reveals plasticity of TGF-beta signaling
BMC Systems Biology 2014, 8:30 doi:10.1186/1752-0509-8-30
- Badges
- Science topic