Activity of Differentiation-inducing Agents and Conventional Drugs in Head and Neck Cancer Xenografts

Abstract

Three putative differentiation inducing agents and five conventional drugs which have been shown to be active in patients with squamous cell carcinoma of the head and neck (HNSCC), were tested for activity against HNSCC transplanted in nude mice. Drugs were administered at a maximum tolerated dose level. By testing the effect of conventional drugs the value of the nude mouse xenograft model for testing new drugs was assessed. Bleomycin as well as cisplatin showed antitumour effects in nude mice, although toxicity and thereby the effectiveness of cisplatin varied during the 5-year period in which the experiments were performed. Bleomycin caused responses in 4 out of 13 tumour lines and cisplatin, when administered at a high dose, was active in 2 out of 5 tumours. 5-Fluorouracil and cyclophosphamide were only moderately active, while methotrexate was inactive. These data indicate that the model might be of value in the detection of new anticancer drugs although it may have a tendency to underestimate the activity of some drugs. We used the nude mouse xenograft model to test the antitumour activity of three differentiation inducing agents, the polar-planar solvents hexamethylene bisacetamide (HMBA) and N,N-dimethylformamide (DMF) and the antimetabolite 5-aza-2'-deoxycytidine (5-aza-dCyd). HMBA appeared to be inactive. In contrast, DMF was active in 1 out of 4 tumour lines while 5-aza-dCyd was active in 2 out of 5 lines tested. Furthermore, the whole panel of differentiation inducers and conventional drugs was tested for antitumour activity against three HNSCC tumour lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal models for the study of squamous cell carcinoma of the upper aerodigestive tract: A historical perspective with review of their utility and limitations. Part A. Chemically‐induced de novo cancer, syngeneic animal models of HNSCC, animal models of transplanted xenogeneic human tumors

“…Their results showed that the model might be of value in the detection of new anticancer drugs, although it may have a tendency to underestimate the activity of some drugs. 139 A significant disadvantage to the xenograft animal model is that less than 2% of human tumor explants metastasize when placed subcutaneously in nude mice. 140 Increased concentrations of NK cells in nude mice may explain resistance to metastasis.…”

In vitro models as tools for screening treatment options of head and neck cancer

“…Next to in vitro models for cancer research, HNSCC xenograft mouse models, which mimic the physiological and pathophysiological complexity of tumors, were already introduced more than 30 years ago ( 37 – 39 ). For many years these models represent the industrial gold standard for the development of cytotoxic cancer therapies and targeted therapies and for monitoring their efficacy employing human cancer cell lines/tumor tissues engrafted into immunocompromised mice to evaluate pharmacology, efficacy, and safety profiles of the agents to be tested ( 40 – 42 ).…”