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In vivo-Like Drug Responses of Human Tumors Growing in Three-Dimensional Gel-Supported Primary Culture
Robert A. Vescio, Charles H. Redfern, Theodora J. Nelson, Scott Ugoretz, Peter H. Stern and Robert M. Hoffman
Proceedings of the National Academy of Sciences of the United States of America
Vol. 84, No. 14 (Jul. 15, 1987), pp. 5029-5033
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/30323
Page Count: 5
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An in vitro test of cell sensitivity to drugs that indicates in vivo response is an important need in cancer therapy and cancer drug development. Toward this end, we previously developed a collagen gel-supported culture system for growth of human tumors. This three-dimensional culture system is general and grows tumors at high frequency directly from surgery or biopsy that maintain important in vivo properties in vitro, including tissue architecture. We report here that with autoradiographic techniques measuring cellular DNA synthesis the drug responses of individual cells within the tissue structure of in vitro-grown tumors can be determined. Twenty tumor classes, including all the major ones, have been measured in toto at >50% frequency. Quanitative and qualitative results show increasing cell kill with rising cytotoxic drug concentration, differential drug sensitivities of multiple cell types within individual cultured tumors, differential sensitivities of a series of tumors of the same histopathological classification to a single drug, differential sensitivities of individual tumors to a series of drugs, and sensitivity patterns of various tumor types similar to the sensitivities found in vivo. Therefore, the results indicate that potentially important therapeutic data can be obtained from tumor specimens growing in vitro for the individual cancer patient as well as for rational and relevant screening for new agents active against human solid tumors.
Proceedings of the National Academy of Sciences of the United States of America © 1987 National Academy of Sciences