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Deceiving tumor cells to think that they are antiviral, what is the new idea of anti-cancer?

via:CnBeta     time:2021/1/16 12:07:07     readed:81

Recently, a special case of new coronavirus has attracted many people's attention: a patient originally suffered from advanced lymphoma, but after being infected with new coronavirus, most of the tumors in the body miraculously almost disappeared. Although the reason for the disappearance of the tumor has not been confirmed, the researchers analyzed that this may be caused by the anti-tumor immune response triggered by virus infection.

In recent years, the idea of stimulating the body's own immune response to fight against cancer cells has become an important strategy for the development of anti-cancer therapy. Oncologists are constantly exploring methods that can be applied in clinical practice.

The top academic journal Cell recently published a research paper, in which scientists revealed in detail how a novel splice some targeted therapies can "cheat" cancer cells and make tumors self destruct by activating their antiviral immune signals. Using this mechanism, we are expected to conquer some extremely difficult cancers.

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The spliceosome targeted therapy in this study focuses on the RNA splicing process. In molecular biology, this means that when DNA molecules are transcribed into single stranded RNA molecules, the fragments that do not encode amino acids in RNA need to be "cut" first, and then the remaining fragments that encode amino acids need to be "spliced". Only through the correct RNA splicing can the correct messenger RNA be formed.

In the past, some studies have found that RNA splicing by drug interference may have a strong impact on some types of tumors, such as triple negative breast cancer.

Triple negative breast cancer is a kind of malignant tumor which is easy to metastasize and relapse. Because the three common receptor molecules in breast cancer cells are negative, it is difficult for endocrine therapy and targeted drugs to work on these cancer cells. This subtype is also recognized as the most refractory breast cancer.

Interestingly, triple negative breast cancer seems to respond to splice targeted therapy. So in this study, scientists explored exactly why. It turns out that this treatment can make cancer cells mistake for virus invasion.

Specifically, in these cancer cells, RNA splicing is interfered by drugs, resulting in many RNA molecules that have not been "clipped" clean. These abnormal long RNA strands accumulate in the cytoplasm, forming a double stranded structure, just like RNA viruses. Recognizing the appearance of double stranded RNA, cancer cells think that they have been invaded by RNA virus, so they start the anti-virus immune signal, which will not only automatically stop - trigger apoptosis, but also stimulate the human immune system, trigger inflammatory response, and enhance the anti-tumor effect.

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Schematic diagram of research

"Now, not only do we have a clearer understanding of how a large number of wrong splicing in breast cancer cells can lead to cellular stress, but we also speculate that this kind of reaction may exist in many other types of cancer and diseases." Dr. jarey Wang of Baylor College of medicine, CO lead author of the study, said.

Even without splice targeting therapy, RNA splicing errors can occur spontaneously in tumor cells, stimulating the immune system, the researchers noted. Therefore, wrongly spliced RNA may be used as a clinical biomarker to help doctors find out which cancer patients are more likely to benefit from immunotherapy.

Professor Trey Westbrook, who led the study, added: "immunotherapy currently works only in a small number of cancer patients. This study reveals a new communication mechanism between cancer cells and the immune system, which will help bring new treatment strategies and benefit more patients. "

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