This method of tumor diagnosis is more "aura" than genetic testing.
March 11, 2019 Source: Science and Technology Daily
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)]; "Even if I am not a drug god, the prototype of the so-called 'targeting medicine', Gleevec, patients will be resistant after 5 years of use." Cheng Shuzhen, academician of the Chinese Academy of Engineering and a tumor economist, said that for several years People hope to use the gene as a clue to "clamp" the tumor, which seems to be difficult to last. "I saw great progress and thought that the tumor would be broken. After a few years, I found that this method is limited."
Can the tracking gene be close to the "truth" of tumorigenesis? With genetic testing and targeted therapy, is it possible to "treat the root cause" in the future? If the tracking gene is going around the road, is there any shortcut?
Recently, the Xiangshan Conference held the 645th academic conference on the topic of “post-genome era and tumor transformation medicineâ€. Discuss new technologies and possible futures for multidisciplinary treatment of cancer.
Genetic mutations are not necessarily "cancer"
A "cancer" cell undergoes a genetic mutation, but a cell with a genetic mutation does not necessarily undergo canceration.
In order to understand what caused the "cancer", we must first understand the characteristics of the tumor cell genome, the United States major research project "The Cancer Genome Atlas" (TCGA) launched in 2006, is expected to cost 100 million US dollars However, after several times of capital recovery, the expenditures far exceeded the budget. Gene sequencing analysis was performed on 33 10,000 human tumor samples, and scientists from 16 countries collaborated to discover nearly 10 million cancer-related mutations.
“They finally identified 299 cancer-driven genes.†Cheng Shuzhen said, but clinically, people have discovered the problem of “unpredictableâ€. Different people of the same type of tumor have different genetic mutations; even the same tumor of the same patient. There are also differences in genetic mutations between different cells inside.
If cancer-driven genes are the decisive factor for "cancer" or not, how can there be a different path? The tumor gene mutation theory is challenged.
The targeted anti-cancer drug Gleevec is effective because of the "alteration" of the cells caused by the translocation of chromosomal DNA, but the emergence of its resistance indicates that new mutant cells will appear, and find a way to "escape" There is a channel for Gleevec's control.
"If you fully understand the occurrence, development and evolution of tumors from the root cause, it is difficult to lock the key to cure the tumor in time and space." Cheng Shuzhen said.
"At present, nearly one hundred molecularly targeted drugs are developed based on gene-related cell carcinogenesis, and have been widely used in the clinical treatment of tumors." Professor Lu Youyong, Department of Molecular Oncology, Peking University Cancer Hospital, Beijing Cancer Institute, said However, the conclusions of these studies are based on limited genetic analysis.
Protein detection is more advantageous. If the gene is a "key", the protein is more like a "lock" - the gene needs to pass the role of the protein to open the "door" to see what happens. However, the problem is that there is a lot of "key" that can be opened by the "lock" of protein.
So, can research start with a more direct "lock"?
"Protein is more downstream, closer to the results." Qin Yu, a professor at the National Protein Science Center, said that as a direct executor of life, protein and genes should have greater advantages in medicine.
The concept of proteomics was born in 1994, but its reputation and popularity are not as good as genomics.
"In terms of detection technology, proteins are very difficult." Qin Hao analyzed the reasons. Because proteins are not amplified like DNA, their large-scale detection has always been challenging.
The invention of high-throughput DNA sequencers has transformed the detection of individual genomes from 13 years to less than half an hour now, and the exponential increase in speed has enabled the large-scale scientific research and clinical use of today's gene sequencing technology. Similar to genetic testing, the more efficient use of chromatographic-mass spectrometers and the complete preparation of proteomic samples, starting in 2013, have given people the means and tools to detect proteomes.
"For protein detection of biological samples, it is necessary to detect more than 10,000 proteins at once." Qin said that to achieve a short time to detect a large number of samples, the proteome technology can be truly applied.
High throughput, large scale, and accuracy are the necessary “three treasures†for detection technology to be able to land clinical applications. “Today, proteomics can achieve high-throughput, large-scale accurate detection of various biological samples, and can depict fine changes in thousands of proteins, including high-dimensional maps of expression, modification, localization, and interaction.†He said.
After having the test data, how do you collect the analysis and get the valid information? "We are equipped with the Tianhe No. 2 computer for big data analysis of biological information." Qin said.
So far, protein detection has become another path that may reveal the mechanism of tumor cell development after gene sequencing. The China Human Proteome Project was also launched in 2014, spending a lot of time doing pre-application exploration.
"We already have topographic maps of the top ten malignant tumor proteome changes, and grasp first-hand accurate information such as tumor signaling pathways and potential therapeutic targets." Qin said that the genome is "innate" in birth screening, disease risk, etc. The judgment of the determinants has been successful, and the proteome will be able to judge the "acquired" factor proteomics-driven precision medicine.
The "secret" of the tumor can be spy. "We found that some of the mutations in the tumor itself no longer encode 'useful' proteins, as if they were 'abandoned'." Qin said that they used the protein level detection method to find the body of the tumor patient. A phenomenon that has never been observed before.
It has been thought that the primary tumor of the tumor is the "source of all evils". Many treatment methods use the primary lesion as the "target" and may not aim at the "focus". "Sometimes, the 'useful' protein in the tissues adjacent to the cancer is extremely active." Qin said that the real blow should be "forward", who are "striking the city" in the patient's body. “But these are just speculations and require more in-depth mechanistic research to be clear.â€
"We also found that the molecular prognosis can be used to accurately predict the prognosis of patients." Qin said that the image of healthy tissue and the image of tumor tissue are drawn, and the differences between different types of tumors are found by comparison, and then according to the treatment, Find the correspondence.
Since 2012, Qin Yu team and the Beijing Cancer Hospital Shen Lin team began large-scale analysis of gastric cancer samples, giving a "portrait" of diffuse gastric cancer. They screened 83 cases of cancer and matched paracancerous tissue samples from 2451 gastric cancer samples, and divided diffuse gastric cancer into three molecular subtypes closely related to survival, prognosis and chemosensitivity.
Three kinds of "portraits" of diffuse gastric cancer patients, like three different "personalities", have significant differences in postoperative chemotherapy effects and survival time. "This study found prognostic-related molecular typing through high-precision resolution of the proteome. Next, we can try to make accurate diagnosis and treatment for different types of diffuse gastric cancer, or other types of tumors." Qin Lan said.
"Proteomics technology has made breakthroughs in recent years." Qin said that it is now possible to quantify more than 8,000 protein products within 6 hours, which is equivalent to the actual protein types expressed in cells, and the detection accuracy is greatly improved. The number of samples can be as low as 10,000 cells, about a few cubic millimeters of tissue. It has been able to meet clinical requirements.
In the future, based on the establishment of a consortium of hospitals, protein testing institutions, and big data analysis organizations, seamless integration of basic research, preclinical research, and clinical transformation can be achieved.
Using protein as a tool to "sniff" tumor "base camp" will not be a multiplier, and it will take time to test. At present, the "China Human Proteome Project" has selected more than ten kinds of tumors such as liver cancer, gastric cancer and lung adenocarcinoma as research objects. The detection data collection has been basically completed, and it has entered the stage of data analysis and fruit production. Liver cancer and gastric cancer have achieved initial results. In the future, proteomes can be used as a basis for clinical treatment in the same way as genomes, and may provide more effective treatment strategies for individual treatments such as individualized treatment, precise treatment, and targeted therapy. And treatment ideas.
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