The next PD-1, Nobel Laureate of "blood and oxygen" opens up a new direction of anti-cancer treatment

In recent years, the PD-1 fire has made many pharmaceutical enterprises taste the sweetness of new drug research and development, and at the same time, they are always exploring the next "PD-1" As a pharmaceutical enterprise, if it can lead its peers in research and development, it may mean hundreds of millions of capital income Just as this time, the 2019 Nobel Prize in physiology or medicine was announced William George Kailin Jr of Harvard Medical School, Peter John Ratcliffe of Oxford University, and Greg Semenza of Johns Hopkins University Medical School in the United States discovered the mechanism of cells' feeling and adapting to different oxygen environment, and revealed how cells adapt to the mechanism of oxygen concentration change At the same time, it has opened up a new research direction for cancer treatment As the drug known as "starved cancer cells" came out some time ago, bevacizumab, which was approved by CFDA of China on February 26, 2010, can specifically bind to vascular endothelial growth factor (VEGF), thus blocking the binding of VEGF and its receptors (flt-1 and KDR) on the surface of endothelial cells, so as to inhibit tumor angiogenesis The drug has also been approved for the treatment of metastatic colorectal cancer, non squamous non-small cell lung cancer, cervical cancer and other malignant tumors In the past few years, bevacizumab, the anticancer drug that has been ranked among the top ten best-selling drugs in the world, can be considered as the first drug to use the "blood oxygen mechanism" It has already treated more than 1 million patients, with annual sales of billions of dollars With this mechanism, perhaps more new drugs have been developed and tested in an orderly way Sales data of bevacizumab in 2018 In 1971, Judah Folkman, the youngest professor in the history of Harvard Medical School, published a paper in the New England Journal of medicine In the experiment, the professor found that tumors can secrete a substance called "tumor angiogenesis factor" (TAF) Although the separation and purification of TAF has not been completed, he believes that, for this kind of substance, the Qualitative inhibition will be an effective anti-cancer strategy Careful students will find that Judah Folkman and the Nobel Prize winner's theory seem to have the same points, or just unify the different stages of the pathogenesis, so it seems to be a preliminary judgment: "this road can go through." Therefore, in my opinion, for the Nobel Prize winning mechanism of medicine, I have summed up two key points: "blood oxygen" core concept: breaking the hypoxia protection of cancer cells, cancer cells will be killed Core mechanism: hypoxia protection mechanism, "hypoxia inducing factor" and "erythropoietin" Perhaps to grasp these, the road of research and development means that there will be a variety of innovative drugs in the future At the same time, the author also inadvertently found that the domestic related academic research work has been involved in a long time Professor Hong LAN, Ph.D in physiology and pathophysiology, School of medicine, Yanbian University, once mentioned in the research progress of hypoxia inducible factor-1 α expression in tumors that HIF-1 α is an important mediator of cells under hypoxia, so it is high in many tumors HIF-1 α is highly expressed in many kinds of tumors, which not only participates in the epithelial stromal process and angiogenesis of tumors, but also participates in the metabolism of tumors, and also plays an important role in the process of tumorigenesis and development Therefore, it is the focus of the next step to further clarify the specific mechanism of HIF-1 α in various tumor processes and to determine whether it can be used as an indicator molecular marker for early diagnosis and prognosis of tumors Further understanding of the influencing factors and regulatory factors of HIF-1 α gene formation will help us to further understand the pathological mechanism of malignant tumors, and it is expected to reduce the expression level of HIF-1 α in various ways to find new effective targets for the treatment of malignant tumors In addition, Chen Yongshun, the Fifth People's Hospital of Zhengzhou City, also mentioned that the increase of HIF-1 α expression can promote the growth and metastasis of tumor in the literature "research progress of hypoxia inducible factor-1 α in malignant tumor" 2006-08-23 HIF-1 can increase the contradiction of blood supply, oxygen supply, energy supply and reconciliation by inducing the expression of VEGF and glycolysis related enzymes By analyzing the expression of HIF-1 α in 179 tumor samples, it was found that there were 13 kinds of 19 types of tumors, including colon cancer, breast cancer, gastric cancer, lung cancer, skin cancer, ovarian cancer, pancreatic cancer, prostate cancer and kidney cancer In view of the important role of HIF-1 α in tumorigenesis and development, inhibiting the expression of HIF-1 α and blocking the transmission of hypoxia signal have become a new research hotspot At last, Professor Chen Yongshun proposed that HIF-1 α, as the core transcription factor regulating hypoxia adaptation of tumor cells, participates in the transcription regulation of many genes and the adaptation of tumor cells to hypoxia Further understanding of the influencing factors and regulatory factors of HIF-1 α gene formation is helpful to further understand the pathological mechanism of malignant tumors, and it is expected to reduce the expression level of HIF-1 α by various methods to find new effective targets for the treatment of malignant tumors This also makes us think whether the thorough analysis of the expression control of HIF-1 α, the Nobel R & D mechanism, may mean that the next PD-1 is coming, and whether it means that the tumor market will usher in another major reshuffle The results show that the new drug market continues to shuffle On the one hand, as a large-scale enterprise, is it a wide spread net with even rain and dew, or is it to choose the best? On the other hand, as a small enterprise without great R & D capability, can it only die in vain? I think the problem may not be as serious as it seems For small enterprises, entrust the authority to do a good job of market research, combined with cro outsourcing market, if the market allows, as long as there is a heavyweight innovative drug with a famous name, do you still worry about being eliminated? Once the first step is taken, the follow-up is not as hard as you think! In the same way, large enterprises are more like this Sufficient financial support means more opportunities, and there will be no hesitation After all, "money really can do whatever you want" But for the market, at that time, no matter how large or small enterprises have their own unique innovative drugs, the replacement speed of new drugs will be accelerated, and to some extent, they can imitate the waste of funds The money earned by enterprises will be invested in the research and development of new drugs, and the drugs after research and development will earn money again, so what diseases do human beings need to worry about that we can't overcome? Believe that the next carrelizumab and the next Hengrui may be you! Finally, the bid winning data of carrellizumab is attached Statement: this opinion only represents the author, not the position of yaozhi.com, welcome to exchange and supplement in the message area; if you need to reprint, please be sure to indicate the author and source of the article.