Chinese scientists draw the world's most "toxic" breast cancer multi-omics map
March 11, 2019 Source: Science Network
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March 8th, International Women's Day.
In the early morning of the day, the international oncology journal “Cell Cancer†published an important research achievement completed by Chinese scientists.
Led by Professor Shao Zhimin, Director of Department of Surgery and Director of Breast Surgery at Fudan University Cancer Hospital, and Director of the Institute of Cancer Research at Fudan University, including Executive Director of the Center for Precision Oncology at the Affiliated Tumor Hospital of Fudan University and Prof. Huang Wei from the National Human Genome Research Center of Shanghai Academy of Sciences. Four teams from the School of Life Sciences of Fudan University and Professor Shi Leming of the Affiliated Tumor Hospital of Fudan University and the team of Professor Wang Peng of the Shanghai Institute of Advanced Studies of the Chinese Academy of Sciences have successfully mapped out the world's largest triple-negative breast cancer queue after more than four years of joint research. The omics map and the "precise treatment strategy based on molecular typing of triple-negative breast cancer".
Triple negative breast cancer lacks effective "therapeutic targets"
"Breast cancer is like a 'big family', which can be subdivided into four major subtypes: luminal surface A, luminal surface B, HER-2 positive and triple negative. Among them, triple negative breast cancer is the most 'toxic' type." "Reporter of the Chinese Journal of Science and Technology", "The reason why triple negative breast cancer is called 'three yin' is precisely because of the three main therapeutic targets of estrogen receptor, progesterone receptor and HER-2 of this breast cancer subtype. The points are all negative. Compared with the other three breast cancer subtypes, triple negative breast cancer can only rely on chemotherapy, and the treatment effect is not good, which is a worldwide problem in breast cancer research."
"Anti-cancer drugs have to play a role, they must first find a 'target' on the tumor. This 'target' is what we usually call a drug target, and the drug targets of different tumor types often have a big difference," said Shao Zhimin. Further explanation, "The lack of specific therapeutic targets is the main reason for the long-term lack of good treatment for triple-negative breast cancer."
At present, triple-negative breast cancer treatment is mainly chemotherapy, but even so, a considerable number of patients suffer from the side effects of chemotherapy, and because "blind" chemotherapy is easy to produce drug resistance, it is ineffective, and the recurrence rate after 3 years is also Will reach 40% - 50%; and once the distant metastasis occurs, it is almost incurable.
Drawing the world's largest "multi-group map" of triple-negative breast cancer
Triple-negative breast cancer accounts for about 20% of all breast cancers, and the proportion of young Chinese patients is higher. And more and more studies show that triple-negative breast cancer may not be a single type.
“Previously, Shao Zhimin’s team conducted a study on triple-negative breast cancer with different curative effects, which differentiated three negative breast cancers with different prognosis, and thus provided different diagnosis and treatment strategies: triple-negative breast cancer with poor prognosis, which can be combined with targeted therapy. Chemotherapy strategies to improve treatment outcomes, thus bringing new hopes for treatment, and in-depth scientific questions for in-depth exploration of triple-negative breast cancer: What are the "omics" characteristics and clinical phenotypes of this type of breast cancer? What kind of relationship is this? This is the problem we want to explore in conjunction with this research.†Huang Wei said in an interview, “To this end, the researchers jointly conducted a study on 465 cases of triple-negative breast cancer clinical samples. A multi-omics map of the Chinese triple negative breast cancer cohort."
Through the analysis of huge genetic data, it is confirmed that triple-negative breast cancer is not a single type of traditional understanding - triple-negative breast cancer not only has its own "family", but also has its own "omics" characteristics, which form different Subtypes, and there may be differences in survival between different subtypes and sensitivity to different treatment regimens.
What are the subtypes of the most "poisonous" breast cancer? Previously, no clear answers were given to all three negative breast cancer research topics in the world. The research team used a comparative analysis of a large number of data, and the triple-negative breast cancer subtype with some common features gradually became clear. Based on the different characteristics of these subtypes of surface proteins, the researchers classified triple-negative breast cancers and named them four different subtypes: immunoregulatory, luminal androgen receptor type, basal-like immunosuppressive, interstitial . This is also the first internationally based classification criteria for triple-negative breast cancer based on multidimensional big data systems, which points to a new direction for finding targets for triple-negative breast cancer.
The researchers further analyzed different subtypes of triple-negative breast cancer and found unique genetic loci for different subtypes. “In fact, the naming standards of different subtypes of expert teams are based on the different characteristics of cancer cells.†The first author of the paper, Dr. Jiang Yizhou, said that immunomodulatory triple-negative breast cancer is an example. Compared with other subtypes, this type of breast cancer cells have a large number of lymphocytes around them, which may be sensitive to immunotherapy. In the luminal surface, androgen receptor type breast cancer cells have obvious HER-2 gene mutations, which may be applicable. Targeted therapy.
Research results are transforming clinical applications of triple-negative breast cancer in the future expected to be "targeted therapy." At present, Shao Zhimin team invented the clinical and practical three-negative breast cancer molecular typing method based on the results of previous experiments. Combined with the precise medical genetic testing that breast surgery is vigorously promoting, it can accurately classify and identify drug targets for each patient. Point, which is expected to achieve precise treatment in the clinic.
It is reported that the Fudan University Affiliated Tumor Hospital has carried out a clinical study on the precise treatment of refractory triple-negative breast cancer, the FUTURE study, which was approved by the ethics committee and attempted to identify the individual gene variants in triple-negative breast cancer. The characteristics of the points are precisely divided into seven different targeting arms. The naming of this clinical trial also represents its connotation. The future direction of triple-negative breast cancer is classified and treated. It is no longer a distant dream to improve the survival of patients with triple-negative breast cancer. For patients with advanced triple-negative breast cancer who are resistant to chemotherapy, it can be said that it brings vitality and dawn.
Shao Zhimin said that the unique genetic mutations of different subtypes are the "aviation marks" of clinical transformation research, which breaks the difficulty of the "ambiguity" of the treatment of triple negative breast cancer in the past and helps medical experts to "target". Based on basic research data, the researchers also proposed a "precise treatment strategy based on molecular typing of triple-negative breast cancer." In response to these special gene mutation studies, combined with clinical trials, there is an opportunity to achieve clinical conversion earlier, and to develop drugs for different triple-negative breast cancer targets, so that patients can get accurate and significantly improved treatment options as soon as possible.
At the same time, this study also published for the first time a group of Chinese-negative breast cancer-specific gene mutations: for example, the PIK3CA gene mutation, the proportion of patients with triple-negative breast cancer in China is significantly higher than the data in Europe and America.
"The multi-omics map of Chinese triple-negative breast cancer drawn in this study will help to find more specific targets for patients with triple-negative breast cancer in China, and to develop drug development and clinical trials for Chinese triple-negative breast cancer. The trial provides support for data and evidence." Huang Wei said that in the future, these "omics" and clinical big data will be integrated for interdisciplinary collaborative innovation research, in order to expand the means and scope of clinical transformation research, and then to make malignant tumors such as triple-negative breast cancer and other serious harm to human health. Accurate diagnosis and treatment is possible.
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