Cervical Cancer Patient-Derived Orthotopic Xenograft (PDOX) is Sensitive to Cisplatinum and Resistant to Nab-paclitaxel

Abstract

Background Cervical cancer is a world-wide problem that requires transformative therapeutic strategies. We have previously developed patient-derived orthotopic xenograft (PDOX) nude-mouse models of this disease. In the present report, we demonstrate that the standard drug, cisplatinum (CDDP), is highly-effective while the new, highly-touted agent, nab-paclitaxel (NAB-PTX) is ineffective. Materials and Methods Cervical PDOX tumors were grown on the cervix of nude mice for 4 weeks after surgical orthotopic implantation (SOI). Tumors were treated with CDDP or NAB-PTX. Results H&E staining demonstrated that the PDOX tumor recapitulated the original patient tumor. CDDP was highly-effective. One tumor that was treated with CDDP completely regressed. CDDP-treated tumors were smaller (tumor volume ratio: 0.42±0.36) than the control group (tumor volume ratio: 3.47±1.66) (p<0.01). In contrast, NAB-PTX did not show significant efficacy on the cervical cancer PDOX model (tumor volume ratio: 2.85±1.45) (p=0.47). CDDP-treated tumor weight (50±50 mg) was significantly less than control (238±114 mg) (p<0.01). NAB-PTX-treated tumors were not reduced in weight (246±136 mg) compared to control (p=0.91). There were no significant differences in mouse body weight between groups. Histological evaluation demonstrated that CDDP-treated tumors were fibrotic with scattered squamous cell nests compared to control or NAB-PTX-treated tumors. Conclusion The results of the present study demonstrate the power of PDOX models of cervical cancer to distinguish efficacy of potential therapeutics for individual patients with this disease.

Chimeric Antigen Receptor–modified T Cells Repressed Solid Tumors and Their Relapse in an Established Patient-derived Colon Carcinoma Xenograft Model

“…However, these models have been rarely used to evaluate cellular immunotherapy products. PDX models from various tumors, including gastric cancer,15 melanoma,16 ovarian cancer, glioblastoma,17 cervical cancer,18 and breast cancer19 have been developed. Most of these models were derived from surgical specimens 20–23.…”

Recombinant methioninase effectively targets a Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model

“…PDOX models were established from patients with colon [ 14 – 16 ], pancreatic [ 17 – 28 ], breast [ 29 ], ovarian [ 30 ], lung [ 31 ] and stomach cancer [ 32 ], and mesothelioma [ 33 ] in our laboratory, resulting in primary and metastatic tumor growth very similar to that of the patient [ 32 ]. Recently, PDOX models of sarcoma have been developed [ 34 – 38 ], as well as for cervical cancer [ 39 – 41 ] and melanoma [ 42 – 44 ] in our laboratory.…”

High Efficacy of Pazopanib on an Undifferentiated Spindle-Cell Sarcoma Resistant to First-Line Therapy Is Identified With a Patient-Derived Orthotopic Xenograft (PDOX) Nude Mouse Model

“…In order to pursue the goal of precision individualized precision medicine, our laboratory pioneered the patient‐derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). PDOX models thus far developed are pancreatic [Fu et al, ; Hiroshima et al, ,, ], breast [Fu et al, ], ovarian [Fu and Hoffman, ], lung [Wang et al, ], cervical [Hiroshima et al, ; Murakami et al, ], colon [Fu et al, ; Metildi et al, ; Hiroshima et al, ], and stomach cancers [Furukawa et al, ], sarcoma [Hiroshima et al, ,; Kiyuna et al, ; Murakami et al, ,], and melanoma [Yamamoto et al, ; Kawaguchi et al, ,]. PDOX models of sarcoma that we have developed include undifferentiated pleomorphic sarcoma (UPS) [Murakami et al, ; Kiyuna et al, ], follicular dendritic cell sarcoma (FDCS) [Kiyuna et al, ], rhabdomyosarcoma (RMS) [Igarashi et al, ], Ewing's sarcoma [Murakami et al, ], and osteosaroma [Murakami et al, ].…”