The story of HER2 and breast cancer: the most feared thing in the world is seriousness and persistence

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Every October is the “International Breast Cancer Prevention Month”. With the wheel of the times rolling forward, the treatment of breast cancer has moved from “one size fits all” and non-differential chemotherapy to precise targeted therapy and immunotherapy.Behind every step forward is the effort of countless researchers day and night.On September 10, 2019, the Lasker-Diebeki Clinical Medical Research Award, which was called the Nobel Prize vane in the medical profession, was awarded to three scientists (H. Michael Shepard, Dennis J. Slamon and Axel Ullrich) who inventedThe first monoclonal antibody trastuzumab, which blocks carcinogenic proteins, significantly reduces the risk of recurrence of early and metastatic breast cancer and prolongs patient survival.More than 20 years of marketing has saved the lives of countless breast cancer patients and become a model for targeted therapy.From the discovery of the HER2 gene to the successful marketing of trastuzumab, scientific research has never been smooth.In the late 1970s and 1980s, the rapid development of new molecular biology technologies promoted biological understanding and gene cloning of various steroid and peptide hormone growth factors and their receptors, bringing therapeutic drug development.hope.Among them, epidermal growth factor EGF and its receptor EGFR were found.The human epidermal growth factor receptor family includes four members – HER1, HER2, HER3 and HER4.As transmembrane proteins, they bind to growth factors on the cell surface to signal and regulate cell growth, division and repair.Three members of the family, HER1 (also known as EGFR), HER3 and HER4, bind to at least 11 known peptide ligands, resulting in a combination of these two receptors (like dimerization or heterodimerization)And subsequent downstream tyrosine kinase signal transduction chain reaction.These signal chain reactions then stimulate cell proliferation, metastasis, infiltration, and survival, becoming a hallmark of cancer.However, HER2 has no known ligand, but is the preferred dimerization partner of the other three receptors.In 1987, this was also a milestone in the history of breast cancer treatment. The Dennis Slamon team at the University of California, Los Angeles School of Medicine published a study in the science of vibration. About 20%-30% of breast cancers have HER2 gene expansion.Increased or overexpressed, the presence of excessive HER2 leads to uncontrolled cell proliferation and tumor development, and this part of the patient has a lower survival rate and a faster recurrence.Based on these findings, HER2 has undoubtedly become a potential therapeutic target for breast cancer.The target was found, but how to align it is a problem.In 1988, Professor Slamon’s team successfully produced a murine antibody that binds and inactivates HER2. This antibody is used to treat HER2 overexpressing breast cancer cells in culture dishes. As a result, the cells stop growing and regress and die.Even more surprising is that when he injected Her-2 antibody into a living tumor with tumor in his body, the tumor disappeared.After three years, in the summer of 1990, Professor Slamon and others went through a hard time to finally create a target drug targeting Her-2 molecule, trastuzumab.But at this time Professor Slamon is facing a shortage of funds and outside doubts.After several twists and turns, Professor Slamon’s team was finally able to conduct clinical research. The final study included 37 subjects. Most of the patients left for various reasons. Only 5 people completed the trial. Only one of them had complete cancer.disappear.But the news still gives hope to breast cancer patients who have nowhere to go.However, because the drug has not been approved by the FDA, pharmaceutical companies do not want to risk providing unapproved drugs to patients.A gynaecologist named Nelson found that he had applied for “privileged treatment” after he had breast cancer, but the company insisted that it could not be provided if it was not confirmed to be HER2 positive.With the help of the Breast Cancer Prevention Association, Nassell was finally confirmed as HER2-positive breast cancer a year later. However, the news came too late, and Nelson had already passed the drug without a drug.After the Nelson incident, three Phase III clinical trials were conducted in breast cancer patients with the help of the National Breast Cancer Alliance (NBCC) to assess the clinical efficacy of trastuzumab.One of the registration trials, called “648”, included 469 patients with HER2-positive metastatic breast cancer who were randomized to either standard chemotherapy or standard chemotherapy plus trastuzumab. The treatment showed significant differences in one year, and the combination treatment responded.The rate was 53%, the control group was 32%; the response duration was 9.3 months vs. 5.9 months, and the disease progression time was 7.6 months vs. 4.6 months, the improvement of survival rate of trastuzumab reached 30%.Based on the results of the 648 trial, the 1998 FDA approved trastuzumab for the treatment of HER2-positive metastatic breast cancer..
To commemorate the contributions of Professor Slamon, in 2008, a film called The Proof of Survival was released in the United States.The film tells the story of Professor Slamon developing trastuzumab during the eight years from 1988 to 1996.Trastuzumab opened the door to targeted therapy for HER2-positive breast cancer, and no new research on targeted drugs has stopped.On September 10, 2019, the New England Journal of Medicine published a review of Professor Daniel F. Hayes of the University of Michigan Roger Cancer Center: HER2 and Breast Cancer – an extraordinary success story.Professor Hayes said that the oncology community and our patients should thank Ulrich, Shepard and Slammon as well as many other laboratories, translational research and clinical researchers.We must also thank those brave women who have participated in and are participating in the clinical study of HER2-positive breast cancer. These studies have allowed more HER2-positive breast cancer patients to live longer or even be cured. , please do not reprint without the authorization of the copyright owner.


The author ouyangshaoxia