Herceptin's invention team won the Lasker prize in 2019 to understand the 5000 year history of breast cancer

▲ Herceptin invention team, winner of the Lasker Clinical Medicine Research Award in 2019 (photo source: laskerfoundation.org ）< br / > when it comes to breast cancer, you should be familiar with itBreast cancer is the second highest incidence of human cancer, and the main cause of cancer death in womenThe history of the battle between human beings and breast cancer can be traced back to the ancient Egyptian era in the 30th century BCIn the Edwin Smith surgical papyrus unearthed by archaeologists from 3000 to 2500 B.C., there are records of breast cancer cases, but for the treatment of breast cancer, the record on the manuscript is "None"< br / >In this paper, the content team of Wuxi apptec will sort out the "past life and present life" of breast cancer treatment to show you how human beings fight wisdom and courage with breast cancer in thousands of years of history< br / > from "black bile" to "cut, cut, cut" < br / > the exploration of the causes of breast cancer can be traced back to the era of HippocratesThe "father of medicine" believes that breast cancer is a systemic disease caused by excessive accumulation of "black bile" in the bodyOn this basis, Galen, a famous Roman doctor, proposed that if the breast tumor is easy to be removed, it can be treated by surgerySince then, breast cancer has officially entered the era of surgical treatment< br / > early literature records show that at that time, breast cancer surgery was mainly simple tumor resection, and the morbidity and mortality were very high, the prognosis of patients was very poorIt was not until the Renaissance that scientists began to delve into breast anatomy and pathogenesis, and surgery began to expand from only removing breast tumors to removing some tissues around the tumors and even the whole breastIn the 18th and 19th century, the concept of "cut, cut, cut" was further "carried forward" by surgeons, because the medical community believed that breast cancer was a local disease, and it was possible to cure this disease by expanding the scope of surgery, with which DrWilliam Halsted, an American surgeon, was included in the history of breast cancer surgery< br / > ▲ DrWilliam hausteder (photo source: John Hstocksdale [public domain]) < br / > in 1882, Dr hausteder founded "radical mastectomy" (also known as "Halsted operation") to expand the scope of resection from breast to surrounding lymph and pectoral muscles According to Dr hausteder, the first stage of breast cancer metastasis is the regional lymph nodes, which then enter the circulatory system and transfer to other parts of the body Therefore, complete removal of the tumor and regional lymph nodes may cure breast cancer, while removal of the pectoral muscles can avoid tumor residues According to the data released by Dr hausteder in 1894, Halsted operation reduced the recurrence rate of breast cancer operation from 58% - 85% at that time to 6%, and the effect was very significant But the procedure has one major drawback - permanent damage to the patient's body, and the researchers later found that it did not improve the overall survival rate of the patient < br / > but in the history of breast cancer surgery, Halsted operation is still of great significance Before the first half of the 20th century, Halsted operation has been the gold standard of breast cancer surgery Until the middle of the 20th century, scientists gradually realized that breast cancer is a systemic disease from the onset, blind expansion of the resection area can not improve the prognosis of patients, Halsted operation began to gradually withdraw from the stage < br / > endocrinotherapy caused by dairy cattle < br / > in the half century after Halsted operation, the treatment of breast cancer has ushered in a major breakthrough In addition to the general treatment of radiotherapy and chemotherapy, a unique treatment of breast cancer has quietly emerged < br / > at the end of the 19th century, George Beatson, a British surgeon, found that some breast cancers became temporarily smaller after menopause Beatson, who used to work on a Scottish ranch, knows that ovariectomy can prolong the lactation period of cows These two phenomena led to Beatson's bold conjecture that human ovary may also control the proliferation of breast cells < br / > After ovariectomy, the tumor growth of three patients with advanced metastatic breast cancer was inhibited In 1896, when the research results were published in the lancet, it attracted wide attention of the medical community, and since then, it has started the endocrine therapy of breast cancer Mr Beatson is also called "father of cancer endocrine therapy" However, the medical community at that time did not understand the mystery It was not until more than half a century later, when the estrogen receptor (ER) was discovered, that scientists gradually uncovered the mystery < br / > today's scientists have found that estrogen, progesterone, growth hormone and other endocrine hormones are closely related to the occurrence of breast cancer Research shows that about 60% of breast cancer is hormone dependent Therefore, scientists can inhibit the growth of these cancer cells by developing anti hormone drugs < br / > in 1978, tamoxifen, the first anti estrogen drug, was approved by the US Food and Drug Administration (FDA), marking that breast cancer officially entered the era of endocrine drug treatment In the past 40 years, the endocrine therapy of breast cancer has made great progress In addition to the selective estrogen receptor modulator represented by tamoxifen, the third generation aromatase inhibitors and gonadotropin releasing hormone agonists have also appeared Compared with surgery, radiotherapy and chemotherapy, endocrine therapy is more targeted and selective, with less side effects < br / > So why is Herceptin holy? Why did its team of inventors win this award? It all starts in the 1970s < br / > in the mid-1970s, with the deepening of human gene research, scientists gradually found that some genes in our body can induce cancer As a result, scientists began to search for "accomplices" of cancer cell growth genes < br / > in 1985, Axel Ullrich, a Genentech scientist, and his colleague art Levinson discovered a gene similar to the human epidermal growth factor receptor (EGFR, also known as HER1), so they named it HER2 But at that time, Genentech didn't know what it was for It wasn't until the summer of 1986 that Dr Ulrich shared the story of HER2 in a seminar that Professor Dennis J slamon of UCLA found out the importance of HER2 So the two men fell in love and began their cooperation for many years < br / > in 1987, Professor schleman's team reported the association between HER2 and breast cancer: in about 30% of breast cancer cells, the expression of HER2 gene is extremely high, even up to 100 times of that of normal cells! Follow up studies have found that in breast cancer patients, the higher the HER2 gene expression, the worse the prognosis and the faster death This amazing discovery brought researchers a flash of inspiration: if the "accomplice" HER2 is controlled by drugs, it should be able to treat such breast cancer patients < br / > but what kind of drug can attack the target of HER2? Scientists at Genentech have focused on the body's immune system's protein, antibody, against bacteria and viruses Because HER2 is a receptor protein, it needs to be combined with ligands to play a role, so scientists hope to inhibit the binding of HER2 with ligands through antibodies, and then inhibit its function But when Dr h Michael Shepard and his colleagues succeeded in designing antibodies that could be used in human therapy, the euphoria was dashed with cold water At that time, Genentech's first clinical trial of cancer therapy just failed Gene tech, who is still in its infancy, decided to stop clinical trials of HER2 and stop taking the risk of continuing to support the new drug development, which has not yet been successful < br / > the withdrawal of gene tech once brought HER2 project to the edge of death However, the scientists involved in the project by Professor schleman and Genentech did not give up During that time, Professor schleman often came to Genentech's office building to stop passers-by and introduce them to the impressive research data of HER2 project Coincidentally, Genentech's mother, a vice president of Genentech, was found to have breast cancer at that time, knowing how much breast cancer patients need newer treatment options As a result, he became a supporter of HER2 A large number of patients who have no medicine to treat have also expressed their willingness to participate in clinical trials In this way, with the concerted efforts of all parties, Genentech finally restarted the project < br / > September 25, 1998, a day that will be remembered by Professor schleman and Genentech After ten years of research and development, Herceptin, the first HER2 targeted drug, was finally approved for marketing In terms of efficacy, the one-year mortality rate of breast cancer patients receiving chemotherapy alone is 33%, that is, one third of the patients will die within one year When chemotherapy was combined with Herceptin, the death rate was reduced to 22% < br / > laskerfoundation.org ）< br / > after the advent of Herceptin, scientists began to understand the role of HER2 in cancer, and continue to explore and develop a series of targeted drugs with different mechanisms targeting HER2, It includes perjeta (pertuzumab) and kadcyla (ADO trastuzumab emtansine) of Roche, tykerb (lapatinib, lapatinib) of GSK, nerlynx (neratinib, lenatinib) of Puma biotechnology, and irinib (pyrrolatinib maleate) of Hengrui medicine < br / > As the first monoclonal antibody drug targeting oncoprotein, Herceptin has benefited 2.3 million breast cancer patients since it was launched on the market It has become a "life-saving drug" for women with breast cancer, which is why Herceptin's invention team won the Lasker Clinical Medicine Research Award in 2019 Here, we salute the scientists who turned this discovery into innovative therapies, and the patients who bravely participated in clinical trials! < br / > uncovering the veil of heredity < br / > in addition to the research team of HER2, other scientists have also made significant breakthroughs in the research of the causes of breast cancer In 1990, Mary Claire king, then at UC Berkeley, taught