Gettysburg Medical News
The Clinical View
by P.E. Hoffsten, M.D.
28 November 2001

WHAT IS APOPTOSIS?

     For many people, this column will introduce a new word and a new concept about cancer and it’s treatment.    The new word is apoptosis.  It is pronounced just like it is spelled.  It has four syllables.  The first syllable is “A”.  The second syllable “POP”.  The third syllable is “TO” and the fourth syllable is “SIS”.  When you put them all together, they pronounce very easily as “A-POP-TO-SIS”.

    While this word has been in scientific circles for many years, it has taken on new importance in regards to cancer research.  It is defined as programed cell death.  As the body develops and functions as an adult, there are cells that grow, serve a purpose, and then are no longer needed.  The body needs a way for these cells to be neatly and efficiently removed so that new cell growth and other important structures can develop.  It is now known that written in the same DNA instruction manual on the inside on every cell are the instructions on how disappear.  That instruction manual not only has information on how to grow, how to function, but also how to leave when no longer necessary.  That process of how an unnecessary cell will exit is called apoptosis.

    For years the general public had received information that cancer represents uncontrolled cell growth.  The concept that the tumor grows very fast as compared to normal tissues is a generally held concept.  And yet, medical science is aware of many, many tumors that grow very, very slowly as compared to the lining of the intestinal tract which is grown new every 3 days.  Tumor cells may take months before growth occurs.  Thus, the idea that cancer represents uncontrolled rapid growth is not universally true and, in fact, may be a general misconception

    What would happen if a tumor or cancer represented failure of  apoptosis as opposed to uncontrolled rapid growth?  What if certain cancer cells had simply lost the instruction manual for apoptosis and were still growing at a normal rate?    Such a tumor might grow slowly;   without apoptosis the cells would not die and be removed at a normal rate and therefore, the tumor gets bigger and bigger.  Our classical concept of  chemotherapy is to slow the rate of growth of a tumor.  If nothing is done to stimulate the removal of the tumor cells that are already there, effective treatment of the tumor is meager at best.

    There is a rare and unusual disease called familial polyposis in which the individuals grow hundreds of polyps in their colon.  Polyps are outgrowths from the wall of the large bowel that hang into the bowel rather like a grape.  Patient’s with familial polyposis may grow hundreds of these from one end of the colon to the other.  They have little affect during the early years of life, but beginning about age 20 on, these polyps tend to change into cancers and these individuals have a very high incidence of cancer of the colon.  Many years ago, it was observed that individuals with this type of illness who took the aspirin-like products called nonsteroidal anti-inflammatory drugs (Motrin, Aleve, Nuprin, Naprosyn) had a decreased incidence of having polyps in their colon.  When medical researchers began to study this observation, they found that the polyps that turn into cancers in these patients had a very high level of a chemical that could be inhibited through the use of the aspirin-like products.  It is thus now recommended that patients that have familial polyposis take one of the new medications called Celebrex.  This has been shown clearly and definitely to cut down the rate of growth of polyps in the colon and thereby,  prevent the cancers that would normally develop.

    As an outgrowth of this research, it was found that there was also a large amount of chemical in some cancers of the colon and that this chemical could be inhibited with the use of the same drugs to treat familial polyposis.  It appears, that one of the basic problems of cancer of the colon, is not so much a rapid growth of the tumor cells as it is the failure of apoptosis.  It would appear that Celebrex stimulates apoptosis in these colon cancers and thereby prevents the problems normally caused by cancers. It thus appears that there are drugs that can stimulate apoptosis and thereby decrease the size of tumors in the colon.    Then while the tumor might continue to grow at whatever slow rate it does, the death and removal of the tumor cells can be sped up so that the tumor would never really increase in size and cause the problems that cancers do.

    The story is too long to continue in one column so next week the story of a very courageous individual who is benefitting from the above concepts will be told.  The drug used to treat this individual is a simple prescription medication with minimal side effects and yet a very effective impact on his cancer of the colon.   On Saturday morning, December 1, 2001, there will be a discussion on treatment and prevention of cancer at the Medicine Rock Café at 10:00 am.