Collagen gel droplet-embedded culture drug sensitivity testing in hard palate cancer-predicted antitumor efficacy of cetuximab: A case report

Abstract

Abstract.In vitro anticancer drug sensitivity assessments have been performed for various types of cancer, and an association with clinical response has been observed. The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) is an in vitro anticancer drug sensitivity test that has recently reported to be useful in oral squamous cell carcinoma (OSCC). CD-DST allows for the analysis of a smaller number of cells compared with other anticancer drug sensitivity tests. The present study reported a successful analysis of anticancer drug sensitivity using CD-DST on cervical lymph node tissue dissected following neoadjuvant chemotherapy from a 55-year-old man with advanced hard palate cancer. Tumor resection and bilateral neck dissection were performed following neoadjuvant chemotherapy (docetaxel + cisplatin + 5-fluorouracil; TPF) for hard palate cancer T2N2cM0. Local recurrence and cervical multiple skin metastasis occurred ~8 months after surgery, and the patient received six doses of cetuximab (C-mab) + cisplatin + 5-fluorouracil (C-mab + PF) administration, which is a type of molecular-targeted therapy. Following the use of the CD-DST method, the clinical response was noted as stable disease following execution of TPF and partial response following execution of C-mab + PF. In addition, low sensitivity by TPF and high sensitivity by C-mab + PF were reported. The CD-DST method reflected the clinical response for the patient, and the results of the current study indicate that CD-DST is a useful tool for selecting chemotherapeutic drugs for patients with OSCC. IntroductionThe recent introduction of the anticancer drug cetuximab [an epidermal growth factor receptor (EGFr) inhibitor: C-mab] as a molecular-targeted therapy for treating head and neck cancers has expanded the scope of anticancer drugs for treating these cancers. However, no biomarkers are currently available that can predict C-mab efficacy against oral squamous cell carcinoma (OSCC); therefore, it is typically administered irrespective of patient sensitivity (1). Hence, we investigated C-mab use with the collagen gel droplet-embedded culture drug sensitivity test (CD-DST). Kobayashi et al (2,3) developed CD-DST which combines the collagen gel droplet culture method, a simple method of three-dimensional (3D) culture that allows a very small number of clinical samples to be tested with a serum-free medium step and quantitative evaluation by image analysis. CD-DST has little effect on non-cancerous cells, allowing accurate measurements of cancerous cells only. This method has been primarily used on tumors of the digestive system (4-6). Compared to such cancers of the primary organs, OSCC and other oral cancers generally have a smaller tumor volume. CD-DST is, therefore, likely to be a suitable method for testing the sensitivity of anticancer drugs on OSCC. However, there is little application of the CD-DST method to OSCC, with no evaluation of molecularly targeted drugs. In the present study, the CD-DST method was performed using a patient biops...

Identification of the optimal cetuximab concentration that is effective against oral squamous cell carcinoma in collagen gel droplet embedded culture drug sensitivity testing

“…CD-DST, collagen gel droplet-embedded culture drug sensitivity test; CDDP, cisplatin; 5-FU, 5-fluorouracil; PF, CDDP+5-FU; T/C, total colony of the treated cells/total colony of the untreated cells. and compared the results to those of sensitivity testing of PF + cetuximab and its clinical efficacy (20). In the same study, the T/C% of the CD-DST method was found to represent high sensitivity at 32.4%, and the clinical efficacy of PF + cetuximab was consistent with the partial response (20).…”

“…and compared the results to those of sensitivity testing of PF + cetuximab and its clinical efficacy (20). In the same study, the T/C% of the CD-DST method was found to represent high sensitivity at 32.4%, and the clinical efficacy of PF + cetuximab was consistent with the partial response (20). The reported T/C% is 32.4%, which is less than 40% of the cut-off value we determined in the present study, and can be considered to represent high sensitivity.…”

Establishment and Characterization of the Human Tongue Squamous Cell Carcinoma Cell Line NOKT-1

“…This method has advantages in that it allows testing using smaller quantities of cells compared with conventional assays. Furthermore, it eliminates the effects of fibroblasts that can adulterate samples at the time of harvesting and allows the evaluation of physiological drug concentrations [13][14][15][16] . In addition, the CD-DST method can be evaluated by combining multiple anticancer agents.…”

Optimal Contact Concentration of Paclitaxel in the Collagen Gel Droplet-Embedded Culture Drug Sensitivity Test for Human Oral Squamous Cell Carcinoma and Evaluation of Combination with Cetuximab

“…The collagen gel droplet-embedded culture drug sensitivity test (CD-DST), which was developed by Kobayashi et al [11], is an anticancer drug sensitivity test that combines three-dimensional (3D) microcarrier cell culture with serum-free medium and image-based colorimetric analysis [11]. This method has demonstrated high success rates for a wide range of diseases, including OSCC, by overcoming many the limitations of conven-tional chemosensitivity tests [12][13][14][15]. Because CD-DST uses a micro-3D culture, it can be used to evaluate OSCC and other cancers that have low tumor volume.…”