Circumstantial evidence for an association between prior chronic
inflammatory conditions or infections and site-specific cancers existed for
over a century. Except for our ‘accidental’
discoveries on experimental models of acute and chronic ocular inflammatory
diseases that were established at University of Pennsylvania in 1980’s,
little/no data were available on direct association between inflammation and
tumorigenesis. Developmental phases of inflammation-induced
immune dysfunction in conjunctival-associated lymphoid tissues led to tumorigenesis
and angiogenesis in experimental models of ocular acute and chronic
inflammatory diseases. Original
discoveries at UPA, satisfy scientists expressed desires on a) direct
link between inflammation and multistep tumorigenesis, and b) initial
time-course kinetics of inflammation-induced immune dysfunction that would lead
to tumor growth and angiogenesis. Since
1998, at NCI/NIH author’s challenges to promote importance of inflammation in
cancer research and therapy, seem awaked the entire cancer community around the
world. Extension of our pioneering findings lay a foundation to: 1) redefine
acute and chronic inflammation [balance in Yin (tumoricidal) and Yang (tumorigenic)
arms of immune surveillance]; 2) propose immune neuroplasticity
(sympathetic-parasympathetic, adaptive, horizontal); 3) importance of
tissue bioenergetics (mitochondria) in health and diseases; and 4)
challenge validity of heavy investment on ‘inheritance’ (genetic mutations) as
origin of diseases. Ongoing debates,
controversies, lack of understanding and misinformation on what inflammation
does, whether it prevents cancer or promotes cancer will be discussed.