Chemotherapy: Open Access
Open Access

Abstract

Optimal Cetuximab Contact Concentration Using a Collagen Gel Droplet- Embedded Culture Drug Chemosensitivity Test in Human Oral Squamous Carcinoma Cell Lines

Tamura Ryuki, Kaname Sakuma and Akira Tanaka

Objective: There is no established therapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), making decisions regarding anticancer agent use and other treatments difficult. Cetuximab, an anticancer drug used as molecular targeted therapy, is administered irrespective of patient sensitivity due to unavailability of biomarkers predicting its efficacy. We investigated the utility of antitumor effect prediction of cetuximab using collagen gel droplet-embedded culture drug sensitivity test (CD-DST).
Methods: We evaluated 13 human oral squamous carcinoma cell lines (Ca9-22, SAS, SAT, HSC-2, HSC-3, HSC-4, OSC-19, OSC-20, HO-1-N-1, HO-1-u-1, KON, SCC-4, and Nialym). The expression of cetuximab-related genes was confirmed in each cancer cell line using RT-PCR, and CD-DST was used to measure cell line sensitivity to cetuximab and to calculate an optimal contact concentration based on the HNSCC clinical response rate and efficacy rate. Furthermore, CD-DST was performed at this calculated optimal contact concentration using the treatment regimens cetuximab+cisplatin and cetuximab+cisplatin+5-fluorouracil. In vivo assessment was performed in nude mice that were administered cetuximab (250 μg/ml) and cisplatin alone and in combination, and the results were compared with the CD-DST results. Results: Results of RT-PCR showed no specificity. With CD-DST, the optimal contact concentration of cetuximab was 250 µg/ml. An enhanced antitumor effect was observed in some of the cell lines with low susceptibility to CDDP and CF. Antitumor effects for CD-DST and nude mouse experiments were almost equal.
Conclusions: CD-DST can indicate the clinical efficacy of cetuximab. Regarding anticancer drug groups, low-sensitivity cell lines exhibited high sensitivity for regimen including cetuximab, suggesting cetuximab may enhance the antitumor effects of existing cytotoxic anticancer drugs.