A clinically concordant vulvar cancer patient-derived xenograft model retaining primary molecular signature for preclinical drug sensitivity assessment

Abstract Objectives Establish and validate a patient-derived xenograft (PDX) model for vulvar cancer (VC). Evaluate the efficacy of commonly used clinical drugs both in vitro and in vivo using this model. Methods Fresh primary vulvar cancer tumor tissues were then subcutaneously implanted into the scapular regions of immunodeficient mice, with tumor formation monitored and recorded in these mice. Hematoxylin and eosin (H&E) staining was performed to observe and compare the histopathological features of the primary and xenograft tumors, while immunohistochemical (IHC) staining was used to assess the consistency of protein expression profiles between the primary and xenograft tumors. Polymerase chain reaction (PCR) methods were employed to confirm the human origin of the xenograft tumors. Finally, the sensitivity of guideline-recommended chemotherapy drugs was evaluated using both HDST and in vivo efficacy studies, aiming to validate the drug responses observed in vitro with those seen in vivo . Results Tumor tissue from a primary vulvar squamous cell carcinoma patient was successfully transplanted into the subcutaneous region of mice and stably passed to the fourth generation. H&E staining results showed that the PDX model retained the atypia and original histological features of the primary tumor cells. IHC staining further confirmed that the protein expression profile of the xenograft tumors in the PDX model was consistent with that of the primary tumor. PCR humanization identification confirmed that the tumor tissues were of human origin. HDST drug screening results, combined with in vivo efficacy experiments, validated the sensitivity of the PDX model to guideline-recommended chemotherapy drugs, demonstrating clinical consistency. Conclusions We have successfully established a vulvar cancer PDX model. This model retains the fundamental molecular characteristics of the primary human vulvar cancer tumor, thus offering an advantageous approach for preclinical assessment of novel therapies and investigation into the disease’s pathogenesis.