Clinical implications of tumor heterogeneity.

Clinical oncologists have long recognized the great variability in the cellular morphology, natural history, and response to therapy of human tumors. Recent progress in molecular biology, biological chemistry, immunology, and other disciplines has now provided scientists with an array of new technologies that has allowed the study of neoplastic disease to go beyond morphologic and clinical description to examination of the malignant state at the cellular and molecular level. The availability of monoclonal antibodies, DNA hybridization techniques, hormone receptor assays, human tumor stem cell assays, and other methods now enables investigators to reveal, in greater detail than ever before, the great phenotypic and genotypic diversity present in most primary and metastatic tumors. Much of the information obtained thus far has been largely descriptive, cataloging the diversity in karyotypes, immune phenotypes, metastatic potential, drug sensitivity, and other cellular characteristics that commonly occurs in tumors that are seemingly identical morphologically. The origin of tumor heterogeneity is less clearly understood, although the genetic instability inherent in the malignant state appears to be an important element in its generation and maintenance [1, 2]. Tumor het-