SITE-SPECIFIC CHEMOSENSITIVITY OF HUMAN SMALL-CELL LUNG-CARCINOMA GROWING ORTHOTOPICALLY COMPARED TO SUBCUTANEOUSLY IN SCID MICE - THE IMPORTANCE OF ORTHOTOPIC MODELS TO OBTAIN RELEVANT DRUG-EVALUATION DATA

We have developed a novel in vivo model of human small-cell lung carci noma (SCLC) using orthotopic reconstitution by injecting human SCLC in the tail vein of severe combined immunodeficient (SCID) mice whereby the SCLC grows in the lung and other organs. Cisplatin (DDP) had signi ficant antitumor effects on the SCLC growing orthotopically in the lun g whereas mitomycin C (MMC) did not, thereby reflecting the clinical s ituation. However, the opposite effects were found when the SCLC was g rowing subcutaneously, where the tumors responded to MMC and not to DD P. This suggests that the tumors growing orthotopically reflect the cl inical effects of drugs on human SCLC more closely than the tumors gro wing subcutaneously. Therefore, this orthotopic reconstitution model o f human SCLC in SCID mice is thought to be useful for studies on the t reatment of human SCLC and emphasizes the need for orthotopic models f or relevant cancer drug evaluation.