In December 2015, the 39th President of the United States, Jimmy Carter, issued a statement after receiving treatment with the new anti-cancer drug KEYTRUDA (PD-1 inhibitor). He said that after the doctor gave him the latest brain MRI, he did not find it. Melanoma or new cancer cells that appear in his brain. Thus, PD-1 inhibitors have been called "healing the president's antibodies", which has led to widespread concern worldwide for PD-1 immunotherapy.
What is the principle of PD-1 inhibitor treatment?
Which tumor patients have the best effect?
What are the advantages and limitations of chemotherapy and targeted therapy?
How to combine other treatments to further improve overall anti-tumor efficacy?
Is it a versatile therapeutic medicine?
With these questions, let us approach PD-1 inhibitors in the field of cancer.
The birth of PD-1 inhibitors has indeed brought a huge leap forward in the advancement of oncology: it has achieved breakthroughs across multiple cancers: some advanced patients have achieved long-term survival, arguably in modern anti-tumor The tug-of-war has achieved amazing results, and medical researchers have even concluded that immunotherapy will be the main direction for cancer in the future. Is PD-1 inhibitor really unfavorable? Let's first take a look at its therapeutic mechanism.
First, the treatment mechanism
PD-1 (programmed cell death protein 1) is an important immunosuppressive molecule. Immune T cells are the safety guards of human health. In the human body, some small molecules often bind to receptors on immune T cells, inhibiting their activity. Under normal circumstances, this can prevent security guards from attacking their own people and avoiding oolong incidents. But unfortunately, some tumor cells will also take advantage of this, it will be very embarrassing to produce a ligand called PD-L1, as a protective umbrella, escape the T cell attack. When it binds to the PD-1 receptor on T cells, it inhibits the activity of T cells and puts them into a "dormant" state.
PD-1 inhibition therapy is a novel immunotherapy that relies on tumor cells to evade the immune system. The mechanism of action of PD-1 immunotherapy is to design specific protein antibodies against PD-1 or PD-L1, prevent the recognition process of PD-1 and PD-L1, awaken sleep T cells, and partially restore their cellular functions, thereby Enable T cells to recognize and kill tumor cells.
In short, these drugs block the "spoofing" of tumor cells by T cells, remove the umbrella from tumor cells, and allow T cells to remain active and kill tumor cells.
Second, the scope of application
PD-1 inhibitors have not let us down: the anti-cancer spectrum of small molecule-targeted drugs is relatively narrow, which has brought about breakthroughs in cancer treatment for cancer treatment, and some patients with advanced disease have long-term survival and even clinical cure. . It helped patients with advanced dysentery to increase their 5-year survival rate from 17% to 34%; patients with classic Hodgkin's lymphoma who had relapsed or refractory after autologous stem cell transplantation and brentuximab vedotin achieved 66% effective response.
At present, PD-1 inhibitors have been approved by the FDA, which is strictly known worldwide, for the treatment of nearly ten kinds of tumors, including: black, non-small cell lung cancer, bladder cancer, kidney cancer, head and neck cancer, stomach cancer, liver cancer, Huo Chikin lymphoma and solid tumor of MSI-H...
Precautionary factors for the efficacy of PD-1 inhibitors are also being explored, and it is expected that in the future, when the drug is used, the corresponding benefit population can be found more accurately.
What are the advantages and limitations of PD-1 inhibitor treatment compared with traditional chemotherapy and small molecule targeted therapy?
At present, PD-1 inhibitor immunotherapy and chemotherapy, small molecule targeted therapy is a hot topic often discussed by patients and doctors. At present, our application of the immunological checkpoint inhibitor method for blocking PD-1 actually liberates immune T cells to resist tumors and stimulates their own immune potential. However, PD-1 inhibitors are only effective in some patients, but once it works, the efficacy may last for a long time. However, it is also possible to overkill and attack your normal organization.
Chemotherapy is an anti-proliferative treatment that kills actively growing tissue cells with relatively poor selectivity. Therefore, it is possible to kill normal tissue cells while killing tumor cells.
Small molecule targeted therapy is a change in the shortcomings of chemotherapy. It is a selective killing. Similar to biological missiles, it provides precise treatment for patients with targets. These targets are present in normal tissues, and some targets even Innate existence. Therefore, the targeted treatment toxicity may be less than chemotherapy, but the toxicity caused by targeted therapy can not be ignored.
Each of these three treatments has advantages and disadvantages. Relatively speaking, the side effects of immunotherapy and targeted therapy are generally less than the side effects of chemotherapy.
Everyone refers to PD-1 inhibitors as "anticancer drugs." However, traditional medicine treatment still has a large market. The reason for this is that PD-1 inhibitors have a large defect: low efficiency! In the clinic, PD-1 inhibitors are only effective in about 20% of cancer patients.
To truly achieve the goal of curing tumors, it is imperative to increase the effectiveness of PD-1 inhibitors. All researchers are constantly advancing towards this goal. With the deepening of the research, the immunological combination therapy shows a very superior effectiveness, and the specific rate of control of some tumors achieves a better effect through a specific combination. For example: The US ASCO Annual Meeting in June 2017, the clinical data of the PD-1 inhibitor Keytruda combined with chemotherapy for gastric cancer is impressive. Gastric cancer: 60% effective rate and 92% control rate. E7080, also known as levastatin, is a multi-target inhibitor. At the 2017 European Society of Oncology Annual Meeting (ESMO), E7080 published clinical data for PD-1 antibody Keytruda in combination with E7080 for renal cancer. First-line use is as efficient as 83%.
Is it a versatile therapeutic medicine?
In fact, the success of various anti-cancer drugs is not easy. Many research projects will fail due to various reasons such as design process, patient selection, toxic and side-effect treatment, and follow-up.
PD-1 inhibitors are like a dark horse that stands out from the crowd. From July 2014, the first PD-1 inhibitor was launched, and it has only been more than three years now. PD-1 inhibitors have created miracles in the history of pharmaceuticals, and have been approved for indications such as malignant melanoma, non-small cell lung cancer, kidney cancer, head and neck squamous cell carcinoma, liver cancer, stomach cancer, Hodgkin's lymphoma, etc., and have benefited many cancer patients. . However, as a new drug, we need more research to better understand and control it. Just like the large aircraft, Beidou navigation and quantum communication independently developed by our country, it takes 3-5 years of flight test and test to form a stable operation process and specifications, and master the comprehensive technical parameters and replacement measures to be truly practical. In addition, the efficacy of the drug only benefits some patients, but also need to further find a reliable predictor of efficacy; toxic side effects, T cells overkill formal attacks on normal tissue caused adverse reactions can not be ignored.
At present, there are many PD-1/PD-L1 antibody drugs on the market, and more than 1,600 clinical trials are underway. What is more worthy of our expectation is that many companies in China are also standing out in the R&D competition. Some related clinical researches are also carried out in many clinical medical centers in China. The listing of these domestically produced drugs in the future is expected to alleviate the problem of new drugs being too expensive. It is foreseeable that the wind and rain will be accompanied by the rainbow along the way. There will be many twists and turns, and they will witness many miracles together.
In short, PD-1 inhibitors have brought new weapons and new ideas to our anti-cancer treatment, which is expected to improve the success rate of cancer treatment. However, due to the complexity, dynamic changes and adaptability of the environment, the treatment still depends on the treatment. The fundamental principles of technology, strategy and experience, scientifically and rationally, without over-deification and comprehensive treatment under the guidance of a multidisciplinary team remain unshakable.
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