Guided chemotherapy based on patient‐derived mini‐xenograft models improves survival of gallbladder carcinoma patients

Abstract

BackgroundGallbladder carcinoma is highly aggressive and resistant to chemotherapy, with no consistent strategy to guide first line chemotherapy. However, patient-derived xenograft (PDX) model has been increasingly used as an effective model for in preclinical study of chemosensitivity.MethodsMini-PDX model was established using freshly resected primary lesions from 12 patients with gallbladder to examine the sensitivity with five of the most commonly used chemotherapeutic agents, namely gemcitabine, oxaliplatin, 5-fluorouracil, nanoparticle albumin-bound (nab)-paclitaxel, and irinotecan. The results were used to guide the selection of chemotherapeutic agents for adjunctive treatment after the surgery. Kaplan–Meier method was used to compare overall survival (OS) and disease free survival (DFS) with 45 patients who received conventional chemotherapy with gemcitabine and oxaliplatin.ResultsCell viability assays based on mini-PDX model revealed significant heterogeneities in drug responsiveness. Kaplan–Meier analysis showed that patients in the PDX-guided chemotherapy group had significantly longer median OS (18.6 months; 95% CI 15.9–21.3 months) than patients in the conventional chemotherapy group (13.9 months; 95% CI 11.7–16.2 months) (P = 0.030; HR 3.18; 95% CI 1.47–6.91). Patients in the PDX-guided chemotherapy group also had significantly longer median DFS (17.6 months; 95% CI 14.5–20.6 months) than patients in the conventional chemotherapy group (12.0 months; 95% CI 9.7–14.4 months) (P = 0.014; HR 3.37; 95% CI 1.67–6.79).ConclusionThe use of mini-PDX model to guide selection of chemotherapeutic regimens could improve the outcome in patients with gallbladder carcinoma.

The Development of Next-generation PBMC Humanized Mice for Preclinical Investigation of Cancer Immunotherapeutic Agents

“…The field has reached a point where model specific artifacts have been reduced, resulting in a more accurate bridge between the clinic and murine models. Investigators have replicated patient outcomes to chemotherapeutics in patient-derived xenograft (PDX) recipient animals (93,94), thus providing proof of concept Morillon et al: PBMC Humanized Mice for Immunotherapeutic Investigation (Review) that murine surrogates might predict patient-specific response. These studies open the door for a personalized medicine approach wherein murine surrogates might screen patient-specific response to identify more effective treatment options.…”

Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine

“…22 While there have been descriptions of the establishment of a limited number of biliary tract cancer PDX models, here we describe the largest biliary tract PDX library reported to date. [23][24][25][26][27]…”

Overview of current targeted therapy in gallbladder cancer

“…35 Concomitantly, advanced nanotechnology employing various modified materials that offer optimal cargos to efficiently deliver RNA molecules has also given rise to promising benefit in the chemotherapy of GBC. Cai and co-workers 36,37 found that nanomaterial-induced photothermal therapy in combination with chemotherapy and chloroquine inhibited GBC cell proliferation. It is worthwhile monitoring the efficacy of this novel delivery system with RNA molecules as an alternative therapy for GBC in future.…”