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Cancer Drugs May Be Targeting Wrong Proteins
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Cancer Drugs May Be Targeting Wrong Proteins

Recently, a study by a group of scientist provides the reason for the failure of various cancer drugs in the clinical trials. The research is published in Science Translational Medicine, which highlights that imprecise technology can result in targeting the wrong proteins in the cancer cells. 

For decades efforts have been made to identify the most robust and path-breaking solution to treat cancer. Traditionally, crude methods targeted both healthy and cancer cells which inclined the scientist to find out a more targeted approach. Sooner, researchers came up with a new approach wherein the drugs are developed to target the proteins playing an important role in the survival of cancer cells. 

A breakthrough in drug-based protein target approach was by famous drug ‘Gleevec’. It was known for treating chronic myeloid leukemia but its subsequent clinical trials gave no positive hope. Moreover, some studies show that only 3% of the drugs for cancer in the clinical trials have been approved between 2000 and 2015 which highlights the importance of understanding the reasons behind cancer drug failures.

The study led by Dr. Jason Sheltzer of Cold Spring Harbor Laboratory used CRISPR based gene-editing technology to delete the MELK gene from the cancer cells. In many diseases, cancer cells make a high amount of MELK protein. Studies have shown the role of MELK protein in the progression of cancer cells. Researchers earlier have used drug-based protein target approach to counter the cancer cells. In the present study to confirm this scientist deleted the gene encoding MELK protein to study the impact. Ideally, the growth of cancer cells should be altered but to the surprise, it didn’t. Moreover, when scientist targeted the cells with MELK protein targeting drug, the cells stopped growing even though they were lacking the gene encoding MELK protein. This raised questions among scientist and led to testing 10 more drugs to certain the discovery. All the 10 drugs targeting certain proteins showed similar results highlighting the reason for the failure of many drugs under clinical trials. 

The reason behind these failures could be the use of imprecise or traditional technology used. Earlier RNAi method was widely used wherein the production of the targeted protein is blocked in the cancer cells. If the cells stopped growing then the drug or compound targeting the respective protein would be identified to block the action in the cancer cells. But researchers suggest that there might be a case where RNAi blocks the production of a multitude of proteins making the technology imprecise and thus misguiding the drug developer to identify the exact targets. In addition to this, the researcher also suggests the role of mutations in the cancer cells or the genes encoding protein targeted by drugs which makes the approach inefficient. Thus, scientists now should look at a different approach for the drugs under development pipeline to get better results.

However, this doesn’t bring down the importance of the existing methods. They are indeed important but efforts should be made to target the right proteins. One way to avoid false-positive results during the drug development process is to identify the mutations in the cancer cells. 

This research has opened the pandora box of development that should be looked upon to get the most robust and high throughput approach for cancer drug development. It will not only help in finding better targets but also reducing the failure of drugs at clinical trials. 

Reference – https://stm.sciencemag.org/content/11/509/eaaw8412

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