Xenograft Advances in Oncology

Xenograft is animal tissue implanted into a different species and is often used for evaluating treatment for disease and organ failure. Currently, xenograft mice are derived from established human cancer cell lines, which has “proven useful for identifying cellular and molecular mechanisms underlying metastasis and for developing new therapeutics”.^1The drawback is that these in vitro cell lines do not mimic real tumors that develop in humans, resulting in poor predictive power for many drugs.

Oncology can thank patient derived tumor xenografts (PDTX) in mice for solving this issue. PDTX are human cancer tissue introduced into immunocompromised mice, a process that has proven to be a more stable and effective way to test anticancer drug responsiveness than old models of xenografting. Compared to genetically modified mice and other models, xenografts offer much more therapeutic and clinical insight.

How PDTX works

Immune systems fight off any tissue or biologicals not of its own species and therefore PDTX requires immunocompromised mice in order to prevent an immune response to foreign tissue. Human tissue implanted subcutaneously into mice did not behave as expected and failed to produce the same tumor environment as originally observed in the human. This meant that any therapeutic results found by testing drug compounds in these mice was worthless. Oncology research took a big leap when human tumor xenografts were implanted into the subrenal capsular (SRC) site of mice, as it allowed preservation of histological and stromal elements of the tumor naturally. PDTX became the oncology go-to method of assessing “genomics and proteomics of various cancers, particularly with respect to tumor progression and lack of treatment effectiveness”.¹

Applying PDTX to Oncology Research

In a recent lung cancer study, Moro found that PDTXs “maintain the same characteristics of the human primary tumor for several passages (up to 20), highlighting their value as a resource for multiple studies”.² Moro also found that PDTX models were robust for testing new treatments, as implanted tumors displayed similar responses to common chemotherapeutics for lung cancer tumors. The study believes that PDTXs are highly suitable for “tumor-microenvironment interaction, cancer stem cells identification and modulation after drug treatment.”

While xenograft mice do not offer great insight into biological pathways or immune response, they have advanced oncology greatly by being able to mimic human tumor behavior in a nonhuman. Contract research organizations, such as Oncodesign and Charles River Laboratories, offer human tumor xenograft services for a vast range of cancer, granting access to this valuable method to researchers everywhere.