XI 



CLONAL SELECTION AND 

 NEOPLASTIC DISEASE 



In the last chapter borderline conditions involving prolifera- 

 tion of mesenchymal cells were discussed, with the implicit 

 assumption that malignancy in general was a manifestation 

 of a clonal selection process. This approach to cancer is a 

 standard one — somatic mutation theories of cancer have been 

 current for many years. In this final chapter, only those 

 aspects of the subject which appear to be reasonably relevant 

 to our main theme of the physiological and pathological 

 reactivity of mesenchymal cells will be discussed. 



We may first state in general terms what the somatic 

 mutation theory of cancer entails. On this view, cancer 

 represents the development by a clone of cells (or more than 

 one) of the capacity to multiply freely without regard to the 

 normal controls which maintain cell relationships in the 

 body. This state is reached by a series of mutational events, 

 each of which either results in a selective survival advantage 

 or brings the cell to such a state that a further mutation will 

 endow it with an advantage. 



Some immediate implications of such a view are : 

 (i) that the common forms of cancer will be in cell Hneages 

 which are subject to rapid turnover and in which 

 there is scope for the exercise of selective survival 

 advantage ; 

 (ii) that anything which abnormally accelerates turnover, 

 such as chronic trauma or inflammation, will increase 

 the likelihood of cancer; 

 (iii) that mutagenic agents will be carcinogenic; 

 (iv) that the incidence of cancer will increase steeply 

 with age if two or more consecutive and random 



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