878 METABOLISM OF THE CANCER CELL 12 



and almost unlimited availability of labeled precursors has made it possible to 

 study metabolic pathways in both normal and malignant tissues. Sooner or later we 

 will have definite proof that tumor cells do possess characteristic metabolic 

 features or that they do not differ appreciably from normal cells. 



In order to facilitate the solving of certain of the current problems we should 

 evaluate the existing data as a guide to the most profitable approaches. If sufficient 

 data are not available to provide an answer, further studies will have to be made. 

 Alternatively we should seek new approaches to explain the malignant behavior. 

 Perhaps this behavior may be associated with the response of the normal or malig- 

 nant cell to inherent regulatory factors or to the hormonal factors elaborated by 

 the endocrine or other glands. Hormones must exist, intracellularly or systemically, 

 that regulate or control the metabolic reactions involved in the mobilization of 

 nucleic acids and proteins for cellular division. Finally, the answer to malignancy 

 may possibly depend upon further elucidation of the composition and function 

 of the macromolecular deoxy- and ribonucleoproteins. 



Metabolic studies made on tumors or in tumor bearing individuals extend well 

 beyond the start of the present century. Mliller (1889) and Klemperer (1889) 

 studied nitrogen balance in cancer patients. From the findings of these and sub- 

 sequent investigators the concept has developed that a negative balance may be 

 associated with malignancy. More than fifty years ago, Blumenthal and Wolff 

 (1905), Neuberg and Ascher (1906) and Blumenthal et al. (1909) investigated the 

 proteolytic enzymes in a group of tumors. During the ig2o(s) Warburg and his 

 colleagues (Warburg, 1930) made extensive studies of the oxidative behavior of 

 many normal and malignant tissues. It is obviously impossible to cover all of the 

 metabolic studies related to cancer that have been made over this long period of 

 time or to give credit to the many deserving investigators. Review articles of 

 recent years which cover most of the many diversified areas of tumor metabolism 

 and composition are presented in Table i. In the current review the author 

 has emphasized the coverage of journals publishing studies on the composition 

 or metabolism of tumors from the beginning of 1953 to mid-year 1956. It has 

 also been necessary to include references before 1953 in order to obtain and 

 develop the full significance of a concept. In describing the patterns of malignant 

 tissues, it is imperative that we always refer to some normal counterpart. 

 Chapter i has served as a basis for many of the critical comparisons that have 

 been made between normal and malignant tissues. Some mention must be made 

 of the inerent difficulty encountered in evaluation of tumor data. Such factors 

 as homogeneity of the tumor sample being studied, methodology, expressions 

 of units of concentration or activity, degree of malignancy, species and other 

 influencing factors will be considered whenever these data have been presented 

 in the original publication. 



One of the foremost problems in preparing this chapter was that of a logical 

 organization of the large number of components involved in the overall aspects 

 of metabolism. The great advances that have been made in the area of intermediary 

 metabolism during recent years makes it difficult to consider the carbohydrates, 

 lipids or any other group individually. A complete synthetic or degradative path- 

 way may involve carbohydrates, lipids, amino acids, inorganic elements and aU the 



