HUMAN-TUMOR COLONY ASSAY AND CHEMOSENSITIVITY TESTING

Abstract

The human tumor colony assay (HTCA; clonogenic or tumor stem cell assay) is an in vitro culture system employing semisolid medium support. Using HTCA, the growth and chemosensitivity of clonogenic tumor cells present in fresh biopsy specimens of human tumors can be investigated. Since this technique was described, there has been a marked increase in the direct study of human tumors in vitro. Excellent evidence was obtained which establishes that colonies grown in HTCA are comprised of tumor cells and that clonogenic cells within tumor colonies have the property of self-renewal (the defining property of a tumor stem cell). Chemosensitivity testing with specific agents in HTCA has documented striking degrees of heterogeneity in drug sensitivity from patient to patient, even for tumors of the same histopathology. Clinical correlations were made between in vitro chemosensitivity and the response of patients with metastatic cancer to chemotherapy. In a series of trials, HTCA had a 71% true-positive rate and a 91% true-negative rate for predicting the drug sensitivity and resistance, respectively, of cancer patients to specific chemotherapeutic agents. The assay, thus, appears to be a prognostic factor which identified chemosensitive patients and which in the future may allow some individualization of chemotherapy. HTCA has also had several areas of application to new drug development and screening. While results obtained have been encouraging, ongoing developmental research is needed to improve growth rates for many tumor types and to further improve, standardize and simplify assay methodology. With such improvements, it appears likely that there will be a marked increase in the use of such in vitro human tumor assays for chemosensitivity testing and drug development.