Occurrence of drug resistance in human tumor implanted in nude mice.

A line of human breast tumor xenograft in nude mouse, MX-1, acquired resistance to vincristine or mitomycin C during multiple treatments; both drugs were effective against the parent line of this tumor. If the treatment was started when the tumor was smaller than 500 mm3 in size, MX-1 was responsive to the initial treatment with vincristine (0.8 mg/kg) or mitomycin C (3.4 mg/kg), and some animals survived with complete regression of the tumor. However, some of the recurrent tumors were able to tolerate multiple treatments with either of these agents, and finally acquired apparent resistance to the agent. On the other hand, when tumors larger than 5,000 mm3 were treated with vincristine, the occurrence of resistance was observed with much higher frequency than when small tumors were treated. Resistant tumors thus obtained exhibited significant refractoriness to each agent when they were reimplanted in new mice and treated in the same manner. This suggests that the occurrence of resistance can be ascribed to changes not in metabolic functions of the host animal but in the tumor cell populations.