The reversibility of cancer: the relevance of cyclic AMP, calcium, essential fatty acids and prostaglandin E1.

Transformed cells in culture can be normalised (made to undergo reverse transformation) by exposure to cyclic AMP, prostaglandin (PG) E1 and certain drugs. One of these drugs, thioproline, has been successfully used in treating human cancer. All cancer cells have a number of common characteristics: they exhibit aerobic glycolysis, they fail to show feedback regulation of cholesterol biosynthesis, they do not regulate cytoplasmic calcium levels normally and they produce excessive amounts of 2 series PGs. It has been known since 1975 that transformed cells cannot make PGE1 because of loss of the delta-6-desaturase enzyme which converts linoleic acid to gamma-linolenic acid. There is evidence that PGE1 acting in concert with thromboxane A2 has effects which make it able to reverse all the metabolic abnormalities common to all cancer cells. It is therefore argued that loss of the ability to make PGE1 and/or thromboxane A2 may be the critical step in malignant change in many forms of cancer. Restoration of normal PGE1 synthesis by providing gamma-linolenic or dihomogammal inolenic acids which will by-pass the blocked desaturase, whould be of value in normalising malignant cells and reversing cancer growth. Since this approach is completely non-toxic it is here seriously suggested that it might be used as a first step in treatment of those cancers where current evidence suggests that delay in the administration of orthodox treatment is unlikely to affect prognosis.