Nature publication reveals: why anticancer drugs always fail in human trials

Cancer is a common disease that seriously threatens human health.

Human-derived tumor xenotransplantation (PDX) is a transplanted tumor model formed by implanting tumor tissues and primary cells from patients into immunodeficient mice.

According to statistics, as of July 2020, the world’s first free cancer model portal "PDX finder" has saved 4031 PDX models, and the Mouse Tumor Biology Database (MTB) has saved 19,242 and Papers related to the PDX model.

However, what is puzzling is why many anti-cancer drugs can significantly inhibit the growth of tumors in mice in the PDX model, but they have been repeatedly frustrated in clinical trials?

Recently, researchers from the University of Texas-Houston Health Sciences Center (UTHealth) School of Biomedical Informatics and McGovern School of Medicine jointly published an article entitled "Presence of complete murine viral genome sequences in patient" in the journal Nature Communications.

First, the researchers sequenced the tumor samples of 7 PDX models based on RNA-Seq technology (170 out of 184 conventional RNA sequence samples), and further verified the test results through fluorescent quantitative PCR technology.

In order to further confirm the existence of virus sequences in mouse tumor cells, the researchers isolated and sequenced the RNA molecules of individual cells in PDX tumor samples based on single-cell sequencing technology, and found that the murine virus sequence readings in PDX tumor samples were significantly higher than the original Primary tumor, and the murine virus comes from the tissue and blood inside the mouse PDX tumor cells.

So how do these viruses affect the testing of human anti-tumor drug models? Researchers conducted an in-depth analysis of the gene expression of murine viruses and found that the murine viral load of tumor samples was closely related to the expression of immune genes (such as CD80) in the human body.

The traditional concept believes that because the human tumor tissue transplanted into mice has not been processed, most of the characteristics of primary tumors are retained at the histopathology, molecular biology and genetic level, so it has a good clinical effect.

The development of new anti-cancer drugs has a tortuous and long road.

Reference materials:

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