Researchers Successfully Eliminate Cancer Cells in Mice, Potentially Transforming Glioblastoma Treatment
Understanding Cancer Cells’ Stress Response Mechanism
Glioblastoma, a highly aggressive brain tumor, affects approximately 19,000 people annually in the EU. Conventional treatment options, such as chemotherapy, radiotherapy, and surgery, have remained largely unchanged since the early 2000s. Sadly, the median survival time for patients diagnosed with glioblastoma is only 15 months.
Identifying Stress Response Mechanism in Cancer Cells
A research team, led by Eric Chevet from the French National Institute of Health and Medical Research (INSERM), recognized that cancer cells are fundamentally stressed and exploit stress response mechanisms to their advantage. Specifically, glioblastoma cells employ a protein called IRE1 to enhance their resistance to cancer drugs. The researchers aimed to target this process, known as “target identification,” to weaken the cancer cells.
Promising Results from Computational Modeling and Cellular Tests
In a collaborative effort between INSERM and the University of Gothenburg, the research team pursued a three-step approach. First, they used computational models to screen millions of molecules and identify a potential candidate—Z4P molecule. Next, they conducted cellular tests and discovered that the Z4P molecule not only reduced the cancer cells’ resistance but also blocked their ability to migrate, a crucial factor in the aggressiveness of glioblastoma.
In Vivo Testing and Significant Tumor Reduction
To validate their findings, the researchers conducted in vivo experiments on mice. They combined the Z4P molecule with the chemotherapy drug temozolomide (TMZ) and observed a substantial weakening of cancer cells’ resistance to stress. Additionally, the tumors significantly shrank in size. Notably, when using only TMZ, tumors recurred within 100 to 150 days, while the combination of TMZ and the Z4P molecule resulted in the complete elimination of cancer cells without relapse for over 200 days.
The Road Ahead: More Research and Potential Impact
While these results hold promise, the development of a new drug or treatment is still distant. Further modifications to enhance the effectiveness of the Z4P molecule against cancer cells and extensive animal testing are necessary before human trials can commence. Moving forward, Chevet’s INSERM lab will collaborate with the Rennes Institute of Chemical Sciences to advance the research. Moreover, these findings may have implications for treating other aggressive tumor types, such as pancreatic cancer, triple-negative breast cancer, and certain liver cancers, as highlighted by Leif Eriksson, a co-author of the study and professor of physical chemistry at the University of Gothenburg.
SOURCE: Ref – By Oceane Duboust
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