Need for Ethical Governance on the Implementation and Use of Patient-derived Xenograft (PDX) Models for Anti-cancer Drug Discovery and Development: Ethical Considerations and Policy Proposal.

Patient-derived xenograft (PDX) models, in which tumor tissues resected from cancer patients are transplanted into immunocompromised mice, have been recently considered the most reliable preclinical models that quite accurately stimulate the real-world characteristics and microenvironments of tumors in patients. The ethical uniqueness of the PDX model, which lies in the fact that it is a hybrid of living human tumor tissue and a carrier mouse, raises several ethical concerns. This study presents four ethical points for consideration and a model ethical governance policy for the implementation and use of PDX models for research. First, PDX models carrying living tumor tissues originating from individual patients with dignity must be treated ethically as materials and data in compliance with the principle of respect for persons. Second, although PDX models themselves are patentable and can be commercialized, it is a standard view, as represented by the Oviedo Convention by the Council of Europe, that those living tumor tissues carried by PDX models shall not give rise to financial gain since those tissues are human body parts; therefore, they should be treated according to a recent ethical approach with the custodianship model as the trust property of patients of origin and shall not be subjected directly to monetary transactions. Third, PDX models must be treated with due care in an ethical manner in line with experimental animal ethics. Finally, the implementation and use of PDX models for research purposes must comply with national and international regulations on both animal experimentation and human subject research. These four points should be carefully examined and properly institutionalized as an ethical governance policy in each institution that plans on utilizing or implementing PDX models for research.