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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.


This is obviously a complex and evolving area. Those seeking a general biological introduction to apoptosis can browse the brief intro "What is apoptosis" or pursue the short synopsis in Kimball's Biology Pages. Those seeking more links can refer to the www Virtual Library on Apoptosis. Specifically there is a nice introductory article on cancer therapy and apoptosis in Biospace and a downloadable article on Pubmed by Scott Lowe and Athena Lin called "Apoptosis in Cancer" published year 2000 in Carcinogenesis vol 21 pp 485-495.

Biotech companies developing new cancer treatments based on apoptosis include Aton, Aventis, Gemin, Genentech, Genta, Idun, Introgen, Novartis, Onyx, OSI, SuperGen and one can look under their websites for news relating to their drug development of clinical trial opportunities

Arsenicals (see Ref)

Celecoxib (Celebrex)(see Ref)

COX-2 inhibitors (see Ref)

Curcumin (see Ref)

Gamma-linolenic acid (see Ref)

Interferons (see Ref)

Melatonin (see Ref)

PPAR agonists (see Ref)

PSP (see Ref)

Retinoids (see Ref)

Statins (see Ref)

Tamoxifen (see Ref)

Tocotrienol (see Ref)

Vitamin D (D3) and analogs