CARCINOGENESIS 



best, they can only emphasize weaknesses in our present knowl- 

 edge and help to provide the framework for the design of fur- 

 ther experiments. At this point, it may be appropriate to 

 emphasize a few of the approaches that are worthy of further 

 consideration. 



First, in searching for the causes of cancer and their eventual 

 elimination, it is well to consider the dual roles of initiation and 

 promotion as causal mechanisms in the formation of some types 

 of cancer. Not only must the understanding of the mechanisms 

 by which carcinogens produce heritable changes be clarified, 

 but the inethods by which these processes may be modified must 

 also be investigated. For example, hormones (22,24), caloric 

 restriction (12,67), and irritation influence tumor formation, yet 

 too few investigators are searching for new agents to block hor- 

 mones, for methods to neutralize the favorable influence of 

 caloric excesses on carcinogenesis, and for means to combat the 

 more subtle types of irritation. 



Second, further information is needed about the metabolic 

 patterns which characterize cellular reduplication and spe- 

 cialization. The step-by-step mapping of the individual reac- 

 tions of many alternative pathways forms a large part of the 

 research program at the McArdle Memorial Laboratory (28, 

 39,41,47,48,59,60,68,69). In this work the eventual localiza- 

 tion of the sites of action of antigrowth agents is one of the 

 important goals. This knowledge is required as a firm founda- 

 tion for the chemotherapy of neoplastic diseases and helps to 

 orient our thoughts about the various approaches to therapy 

 One possibility would be to divert cell food from the growth 

 pattern by increasing the level of some quiescent special func- 

 tion. Another would be to supply artificial substrates to the 

 malignant growth process in order to obtain a defective growth 

 mechanism in the cancer cells. 



Third, investigations of the phenomena of invasion and 

 metastasis deserve greater emphasis as another approach to 

 therapy. Additional information is needed concerning the role 

 of fibroblasts, leukocytes, and enzymes in limiting or enhancing 



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