Tumor heterogeneity: morphological, molecular and clinical implications

Malignant tumors are characterized by their great heterogeneity and variabi lity. There are hundreds of different types of malignant tumors that harbou r many oncogenic alterations. The tumor heterogeneity has important morphol ogical, molecular and clinical implications. Except for some hematopoietic and lymphoproliferative processes and small cell infant tumors, there are n ot specific molecular alterations for most human tumors. In this review we summarize the most important aspects of carcinogenesis and chemo-radiosensi tivity of malignant cells. In this regard, some oncogenes such as neu, ras and bcl-2 have been associated with cellular resistance to treatment with a nticancer agents. The knowledge of oncogenic alterations involved in each t umor can be important to correlate the morphological features, the genetic background, the prognosis and the clinical response to treatment with antic ancer agents. Based on the molecular background of the tumor there are new cancer gene therapy protocols. For example using adenovirus E1a in tumors w ith overexpression of neu oncogene, inhibitors of tirosine kinase specific for the PDGF receptor in glioma, inhibitors of farnesil transferase to prev ent ras activity in tumors with mutations in the ras gene.