destroyed by the normal immune system which recognizes the 

 modified cells as "foreign," because of their new surface antigens. 

 Were this the case, an important clue would lie in understanding why 

 the immune system sometimes fails to recognize or destroy the 

 foreign cell, thus permitting neoplasia. 



These few details are offered not so much for the insight they 

 afford into the nature of cancer, but rather to emphasize that, even 

 now, attempts to deal with the disease are limited by the fact that the 

 understanding of neoplasia is still at a primitive, descriptive level, 

 limited by understanding of normal biology. Success in attaining the 

 ultimate goals of the Plan depends upon gathering a sufficient body of 

 information along the lines indicated by the numerous Approach 

 Elements of the National Cancer Program Plan. The possibilities for 

 early diagnosis, for prevention, or for definitive therapy could be 

 markedly enhanced by such knowledge. But even then, considerable 

 additional effort would remain before the Objectives of the Plan could 

 be realized. 



The translation of fundamental understanding into effective 

 therapeutic approaches is a major goal of the Program. Current 

 therapeutic approaches rest on empiricism and a rather general level of 

 understanding. For example, radiation is known to be injurious to cells 

 in mitosis; hence, dividing cancerous cells should be more susceptible 

 to radiation than normal cells. Again, cell division requires synthesis of 

 DNA, the genetic material in chromosomes; hence, chemicals which 

 can interfere with DNA synthesis are candidates for use as anticancer 

 drugs. But both radiation and such drugs have only limited usefulness 

 because of their inefficiency and the fact that they damage normally 

 dividing cells such as those of the bone marrow. What is required is a 

 family of agents directed more closely at the processes involved in the 

 neoplastic transformation. No such agent is available nor can the 

 process in question be described. Even when that knowledge is in 

 hand, the remaining task will be formidable. An illustration of the 

 difficulty of this task may be drawn from another major disease: 

 essential or malignant hypertension. It is now known that this disease, 

 in many instances, is the consequence of an alteration in the kidney 

 which results in liberation into the blood plasma of an enzyme, renin. 

 This enzyme catalyzes the removal from a normal serum protein of a 

 decapeptide, a linear chain of 10 amino acids of known composition. 

 The terminal two amino acids of the decapeptide are removed by a 

 second enzyme contained in normal blood plasma, yielding an 

 octapeptide, a chain of eight amino acids called "angiotension II," the 

 most powerful pressor agent known. If a drug were available which 

 could inhibit either of the two enzymes involved in this process, it 

 could serve as a definitive therapeutic agent for malignant 

 hypertension. Unfortunately, no such inhibitor is known as yet. 

 Alternatively, were there an otherwise innocuous compound which 

 could mimic angiotension but not cause arteriolar constriction, it too 



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