RC:
"Apoptosis" is Greek for suicide and
is also the term for programmed cell death as
occurs in cellular biology. Cells die either
of two ways: by "necrosis" or exteral
force (i.e. homicide) OR via programmed self-destruction(i.e.
suiide). Natural examples of apoptosis abound:
hair falling out, skin cells sloughing off,
a tadpole dropping its tail along its evolution
to a frog ... In any case, apoptosis can be
likened to the trigger that determines cellular
life or death and obviously plays a most central
role in cancer. Cancer cells behave as if there
is a glitch in the software of the cell, turning
it "on" perpetually such that it forgets
to expire as nature would have it.
Therapy would logically then to be to restore
or repair the program such that cells can again
proceed along their apoptotic destiny to extinction.
If we use the analogy of kids attending school
akin to cells maturing, then the eventual graduation
from school is akin to the programmed maturation
or cellular "differentiation" and
eventual death of cells. Cancer cells are like
drop-outs, and "differentiation therapy"
of cancer can be likened to school counsellors
or social workers coaching and coaxing drop-out
kids to go back to school and eventually graduating.
Going back to cancer cells, there is a multitude
of direct and indirect pathways and regulatory
signals involving gene families (p53, Ras, BCL-2),
proteins and enzymes (eg IAPs like survivin,
APAF1, capsases, and cytokines (TNF1, TRAIL,
FAS) and receptors that manipulate and modulate
this literal life and death process.
At the practical level of battling cancer,
most common cancer therapies such as chemotherapy
and radiation is thought to induce apoptosis
which raises the intriguing possibility that
defects in apoptotoc programs contribute to
treatment failure. Then just as there are a
multitude of pathways triggering and controlling
apoptosis, there is an equally large array of
agents which are pro-apoptotic or can induce
programmed cell death. These are also known
as "differentiation" agents and range
from dietary agents (e.g. tea, and tumeric),
fat soluble vitamins (A,D,E)
to herbs, common drugs (COX-2
inhibitors such as celecoxib
or Celebrex and Statins
such as simvastatin or Zocor) to new and investigational
drugs (Arsenic
Trioxide, Phenylbutyrate)[See
below for list of apoptotic agents]. The interesting
aspect about these agents are their relative
independent weakness against cancer with few
exceptions (eg Arsenic
trioxide) and their potential synergism
when applied together as a cocktail. The side-effects
of these drugs are generally mild and they are
perhaps best used in cocktail fashion and in
early or preventative stages. Also personally
noted is the particular usefulness of this therapeutic
approach of "differentiation therapy"
for leukemias/lymphomas and cancers such as
soft tissues sarcomas traditionally resistant
or minimally responsive to chemotherapies or
radiotherapy. I do believe that the eventual
deciphering and unmasking of important trigger
points and signalling pathways of apoptosis
will lead to substantial advance in cancer therapy,
especially with the "cocktail" approach
concurrently targeting multiple signals and
triggers.
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