Tumor animal models used for evaluating the antineoplastic activity of platinum coordination complexes

Abstract

The number of organometallic platinum complexes synthesized and tested for antitumor activity, after the discovery of the antineoplastic properties of cis-dichlorodiammineplatinum(II) (cisplatin), is very high, indicating the interest of numerous scientists in this field. Many experimental models of transplantable animal tumors have been employed for estimating the antitumor potency of these derivatives. Rodent tumors growing in ascitic form, such as Ehrlich ascites carcinoma, sarcoma 180, L1210 lymphoid leukemia and P388 lymphocytic leukemias were widely employed and their use has characterized the first 10 years of research. Solid tumors were used as well. The interest was first addressed to the solid forms of s.c.-implanted Ehrlich ascites carcinoma and of sarcoma 180, and particularly to the s.c.-growing ADJPC6 Plasmocytoma on which many analogs have been tested. B16 melanoma, Lewis lung carcinoma, and specialized forms of implant of human and animal xenografts, in the nude mouse and in the subrenal capsule of the mouse respectively, have elicited the interest of scientists in recent years. In addition, several other transplantable animal tumors have been used: Yoshida sarcoma, Walker 256-carcinosarcoma, VX2 carcinoma, mouse fibrosarcomas. Leukemias such as Dunning ascitic leukemia, Pausher leukemia, MPOC 104E plasmocytoma, and myeloid and lymphatic leukemias of the rat have been used during the last 15 years, giving a clear indication of the broad spectrum of the antineoplastic activity of cisplatin. It is worth noting that, in many instances, more than one single tumor mode1 has been used, although L1210 lymphoid leukemia seems to be the tumor line which has received the most interest, being present alone or with other tumors in almost all of the scientific works from the end of the Sixties. Detailed examination of the tumor models employed in the research for cisplatin analogs shows that, although some old tumors such as Ehrlich ascites carcinoma are still used for studying drug-cell interactions, an even greater interest is devoted by researchers towards an improvement in the selection of experimental tumors endowed with more similarities with those commonly encountered in humans, which are thus more predictive of activity in the human patient.