Mechanisms and markers of carcinogenesis and neoplastic progression

Neoplastic transformation evolves over a period of time involving the progression of the cellular immunophenotype (IP) from normal to hyperplastic to dysplastic, and finally, to fully malignant IPs. Superimposed on these changes is the interaction of the initiated cell with its microenvironment, whereby the neoplastically transformed cells, through the regulation or dysregulation of cytoskeletal, integrin, protease and adhesion molecules, develop a novel manner of relation with their surrounding microenvironment. Studies of the neuroendocrine-immune network revealed that the hormonal and cytokine milieu plays an important role impacting the growth and dedifferentiation capabilities of neoplastic cells. This is further affected by the tumour cells themselves determining the constitution of this hormonal microenvironment, allowing the most aggressive and invasive of neoplastically transformed cell clones to promote their own growth and dissemination. The elucidation of the steps of the progression of cancer from premalignant to metastatic and invasive forms is of utmost importance in the differential diagnosis of neoplasms and in the establishment of more efficacious therapeutic regimens. These regimens will certainly begin to take on a more individualised form. The functional characterisation of various human malignancies as to the neoplastically transformed cells' IP, the bases of their interaction with tissue stromal elements, and the molecules involved in the humoral microenvironment of the particular stage of tumour will certainly allow for the better diagnosis, staging, prognostication and treatment of cancers in the future. This paper reviews carcinogenesis from nutritional, genetic and molecular, and humoral aspects, and discusses the importance of tumour markers in the diagnosis and therapeutic management of human cancer.