Quantitation of Differential Sensitivity of Human-Tumor Stem Cells to Anticancer Drugs

Abstract

With a direct in vitro tumor-colony assay developed to measure sensitity of human-tumor stem cells to anticancer drugs, we performed 32 retrospective or prospective clinical studies in nine patients with myeloma and nine with ovarian cancer treated with standard agents that were tested in vitro. The results were clearly correlated (P is less than 0.00001). Unique patterns of sensitivity and resistance to the six drugs tested were observed for individual patients. In eight cases of myeloma and three of obarian carcinoma in vitro sensitivity corresponded with in vivo sensitivity whereas in one case of myeloma it did not. In vitro resistance correlated with clinical resistance in all five comparisons in myeloma and all 15 in ovarian cancer. We conclude that this assay shows sufficient promise to warrant larger-scale testing to determine its efficacy for selection of new agents and individualized cancer chemotherapy regimens.

Cell aggregates in the soft agar “human tumour stem-cell assay”

“…Recently the soft agar "human tumour stem-cell assay" (HTSCA), popularized by Salmon et al (1978), has attracted attention as a general technique for obtaining colony formation in vitro from cancer cells derived from human solid tumours and malignant effusions. The possibilities that the HTSCA is useful for selection of chemotherapy for the treatment of tumours of individual patients and for identifying in vitro new anti-cancer agents are under investigation in cancer laboratories throughout the world.…”

Experimental combination and single-agent chemotherapy in human lung-tumour xenografts

“…It has been found in this study that only 4/32 patients with metastatic disease from whom xenografts were established survived long enough for predictive studies to be useful. The only realistic hopes at present are in vitro chemosensitivity tests (Salmon et al, 1978) or the in vivo subrenal-capsule system recently described by Bogden et al (1978). Both techniques require urgent and independent validation before their widespread use is justified.…”

Assay of anticancer drugs in tissue culture: Cell cultures of biopsies from human astrocytoma

“…Previous attempts at predictive drug testing (Limburg & Heckman, 1968, Knock et al, 1974, Nissen et al, 1978, Salmon et al, 1978 have relied on relatively short drug exposures, usually considerably less than one cell cycle. The results with HeLa (Freshney et al, 1975) and with glioma (Morgan & Freshney, 1979) showed that observations of less than one cell cycle could often prove misleading.…”