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Development of Biological Diversity and Susceptibility to Chemotherapy in Murine Cancer Metastases

Preclinical Screen Laboratory, Program Resources, Inc. [J. E. T., K. B.], and Cancer Metastasis and Treatment Laboratory, Basic Research Program-LBI [J. M., I. J. F.], National Cancer Institute-Frederick Cancer Research Facility, Frederick, Maryland 21701

We studied the development of biological heterogeneity in a spontaneous melanoma metastasis of clonal origin as demonstrated by karyotypic analysis. The metastatic potential and sensitivity to different chemotherapeutic agents varied both among and within clones of this metastasis isolated either in vitro or in vivo. This finding indicates that, even within a metastasis of clonal origin, cellular heterogeneity for chemotherapy or metastatic potential can develop rapidly and provides a mechanism for the emergence of resistance to therapy. Since most cancer deaths result from metastases that do not respond to treatment, the implications of these findings for the treatment of cancer are clear. Treatment modalities must be designed that circumvent the biological heterogeneity that can develop rapidly within each metastasis and among metastases.

¹ Recipient of support from the National Cancer Institute, Department of Health and Human Services, under Contract NO1-CO-23910 with Program Resources, Inc. To whom requests for reprints should be addressed.

² Recipient of support from the National Cancer Institute, Department of Health and Human Services, under Contract NO1-CO-23910 with Program Resources, Inc.

³ Recipient of support from the National Cancer Institute, Department of Health and Human Services, under Contract NO1-CO-23909 with Litton Bionetics, Inc. Present address: Department of Cell Biology, M. D. Anderson Hospital and Tumor Institute, The University of Texas System Cancer Center, HMB-173, Houston, TX 77030.

Received 7/21/83. Accepted 6/ 4/84.

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