It is even necessary to make a choice between the above groups of cellular constituents and to restrict a monograph such as this to one group, although it is obvious that all groups are inter connected in their role and action. It will be remembered that among the subjects of study functional proteins were mentioned, namely pro teinous hormones, immunobodies and enzymes. The purpose of this treatise is to plead the case for enzymes (standing for holo-, apo-, co enzymes and metal activators) for a number of weighty reasons. Potter196 about ten years ago discussed most admirably the same subject in a monograph of a parallel series of publications. Although a critical review of the subject by Fishman 92 has been incorporated recently into the new edition of Physiopathology of Cancer, the present writer thinks that the time is ripe to reconsider the whole matter in the light of additional experimental work, arguments and conceptional contributions.

Apart from the historical reason, there are practical ones. Enzymes as biocatalysts carry the advantage that they can be assayed more easily than other cellular constituents due to their function and by necessity, through this, include substrates and products of their catalytic activities. They also form, again with their substrates and products, the back bone of the metabolic pathways, so important from the dynamic viewpoint of cellular events, and are closely linked up with all the other biological components, enumerated above, particularly with nucleotides, proteins, carbohydrates, fats, organic phosphates and hormones, the latter having some controlling effect at least on certain enzymic activities. Last but not least, systematic attempts at carcino chemotherapy based on the use of enzymes, coenzymes, or related systems—without ignoring the very important work on antagonists or inhibitors have been somewhat neglected during the years since antimetabolites were first successfully applied in the treatment of acute leukemia by Farber et al.88 In order to proceed with the urgent problem of improvements of such extended chemotherapy it is essential that stock is taken of our present day knowledge in the field of chemistry of enzymes in cancer.

Postulates And Concepts

Usually one starts a building from its foundation but with this review, it is proposed to start from the roof. As in so many edifices of scientific achievements, such a roof is provisional and changeable, in contrast to the less lofty structures beneath.

The principal investigations of the subject under consideration have centered, during the past thirty or forty years, on the question of possible differences between metabolic pathways and enzyme activity levels of normal and abnormal cells, leading to a number of hypotheses and concepts. So far, the majority of studies have been made on experimental tumors of animals and not on human material. It is therefore still largely a matter of conjecture whether all the published results and roof covering hypotheses available can be directly transferred to the more pressing task to obtain a better understanding of the same problems in man.

On several occasions, an assessment of accumulated knowledge in the biochemical field of cancer research has been undertaken. In 1956 the Scientific Review Committee of the American Cancer Society arranged a symposium on "A Critical Appraisal of the Biochemical Characteristics of Morphologically Separable Cancer", 222 and the International Union against Cancer has pursued similar lines during its congresses, the most recent having been held in London in 1958,189 when in section meetings, metabolism of tumors and enzymology in cancer were discussed. During the first part of the 1956 Symposium, the main speakers were Greenstein, Wein house, Potter and Cohen. Three major concepts, particularly with reference to enzymes (with a number of ancillary ones), formed the basis of their deliberations. These concepts, postulates or hypotheses are still with the research workers of today, having been trimmed or expanded according to additional information having become available. Just as history textbooks oversimplify and even distort past events, anyone giving a short account of a scientific hypothesis and its pros and cons might fall into a similar trap. However, here is the gist of the writer's own version.