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Why some cancer drugs may be ineffective

A potential rationalization for why many cancer drugs that kill tumor cells in mouse fashions will not work in human trials has been discovered by researchers with The University of Texas Health Science Center at Houston (UTHealth) School of Biomedical Informatics and McGovern Medical School.

The analysis was revealed at the moment in Nature Communications.

In the examine, investigators reported the intensive presence of mouse viruses in patient-derived xenografts (PDX). PDX fashions are developed by implanting human tumor tissues in immune-deficient mice, and are generally used to assist take a look at and develop cancer drugs.

“What we found is that when you put a human tumor in a mouse, that tumor is not the same as the tumor that was in the cancer patient,” mentioned W. Jim Zheng, PhD, professor on the School of Biomedical Informatics and senior creator on the examine. “The majority of tumors we tested were compromised by mouse viruses.”

Using a data-driven method, researchers analyzed 184 knowledge units generated from sequencing PDX samples. Of the 184 samples, 170 confirmed the presence of mouse viruses.

The an infection is related to vital adjustments in tumors, and Zheng says that might have an effect on PDX as a drug testing mannequin for people.

“When scientists are looking for a way to kill a tumor using the PDX model, they assume the tumor in the mouse is the same as cancer patients, but they are not. It makes the results of a cancer drug look promising when you think the medication kills the tumor — but in reality, it will not work in human trial, as the medication kills the virus-compromised tumor in mouse,” Zheng mentioned.

He hopes his findings will change researchers’ method to discover a technique to kill tumor cells.

“We all share the common goal of hoping to find a cure for cancer. There are 210 ongoing NIH-funded projects relevant to PDX models, with a combined annual fiscal year budget of over $116 million. We need to tighten up quality control and use models that are not compromised so that the treatments we give to future patients are effective,” Zheng mentioned.

This work is a collaboration between the Texas Therapeutics Institute, Institute of Molecular Medicine (IMM) at McGovern Medical School, and the Data Science and Informatics Core for Cancer Research on the School of Biomedical Informatics.

“As a team, we synergized the strengths of McGovern Medical School’s virology research and School of Biomedical Informatics’ data analysis expertise, and it has led to the success of this project,” mentioned Zhiqiang An, PhD, co-senior creator of the examine, professor and Robert A. Welch Distinguished University Chair in Chemistry at McGovern Medical School.

The examine is partly supported by the Cancer Prevention and Research Institute of Texas by way of grant RP170668, RP150551, and RP190561; the National Institutes of Health by way of grants 1UL1TR003167 and R01AG066749; and the Welch Foundation AU-0042-20030616.

Story Source:

Materials offered by University of Texas Health Science Center at Houston. Original written by Jeannette Sanchez. Note: Content may be edited for type and size.

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