FDA has approved 45 small molecule targeted drugs, only 13 of which are listed in China

Cancer has become the most lethal cause of human disease worldwide, and the incidence rate and mortality rate of cancer worldwide continues to rise According to the data of 85.5 million population covered by 72 cancer registries from 2009 to 2011, the National Cancer Center estimated the incidence and death of cancer in China in 2015 It is estimated that in 2015, the number of new cancer cases in China will reach 4.2916 million, with a total of 2.8142 million deaths Lung cancer and gastric cancer are the top two causes of cancer incidence and death in China The second is esophageal cancer, liver cancer, colorectal cancer, breast cancer, brain cancer, cervical cancer, pancreatic cancer, thyroid cancer General situation of molecular targeted drugs tumor molecular targeted therapy is to use the differences in molecular biology between tumor cells and normal cells (such as different characteristics of genes, enzymes, signal transduction, etc.), use drugs that can specifically combine with these target molecules, specifically kill tumor cells, and achieve the purpose of anti-tumor therapy The signal pathway of solid tumor is not single, but generally has multiple channels at the same time The blocking of single target can promote tumor cells to activate alternative signal pathway to obtain antagonistic ability Therefore, the research of multi-target therapy has become a new direction of anti-tumor drug research and development Sorafenib, for example, can be used to treat liver, kidney and thyroid cancer Since imatinib, the first Tinian drug developed by Novartis, went on the market in 2001, anti-tumor molecular targeting drugs have been a research hotspot In this paper, a total of 45 small molecule targeted drugs were counted As of July 2016, FDA has approved 43 anti-tumor small molecule targeted drugs, among which 2 are TiNi drugs not used for tumor treatment, namely, tofetinib for rheumatoid arthritis and rousotinib for myelofibrosis In addition, there are two drugs independently developed by China, namely apatinib of Jiangsu Hengrui and exetinib of Zhejiang Beida The figure below shows the number of molecular targeted drugs approved every year It can be seen that before 2012, the research and development of molecular targeted drugs continued to be popular, with a total of 8 approved in 2012 However, the enthusiasm for targeted drug research and development did not weaken By 2015, another eight molecular targeted drugs were approved Clinical application of molecular targeted drugs: among these 45 small molecular targeted drugs, the treatment of lung cancer and leukemia is the most, 8 each, followed by renal cancer, 7 See the figure below for details (10 of them are multi indication drugs, which have been repeatedly counted) The incidence rate of liver cancer, colorectal cancer, breast cancer, etc., the selectable molecular targeted drugs are few, especially for the treatment of liver cancer only 1 Therefore, the research and development of molecular targeted drugs is in the ascendant, and there are many fields waiting for us to explore Domestic situation of molecular targeted drugs: there are only 13 small molecular targeted drugs on the market in China In addition to apatinib and exetinib, only imatinib and dasatinib have generic drugs in the other 11 drugs, and other drugs are imported from the original research According to the data of sample hospitals in 16 key cities, imatinib is the best selling product, with nearly 400 million yuan in 2015, which is also related to the early listing of imatinib Gefitinib, exetinib, bortezomib and sorafenib are ranked 2-5 respectively In the past three years, the sales of drugs such as lapatinib and acitinib are on the rise, with huge market potential Detailed description of molecular targeted drugs for each tumor In 2015, the number of lung cancer patients and deaths in China was 733300 and 610200 respectively There are 8 kinds of small molecule targeted drugs for the treatment of lung cancer, as shown in the table below There are two main therapeutic targets for lung cancer, one is epidermal growth factor receptor (EGFR), which is represented by gefitinib and erlotinib, the other is anaplastic lymphoma kinase (ALK), which is mainly czotinib and seretinib Among them, alotini and oshitini are the new varieties just launched in 2015 last year At present, the varieties listed on the market in China include the original imported gefitinib and erlotinib, and the independently developed ektinib in China Five other varieties are not yet on the market In 2015, the incidence of gastric cancer in China was about 679100, and the death toll was about 498000 The targeted treatment of gastric cancer started late, and there were few molecular targeted drugs Imatinib is not only a first-line drug for leukemia, but also for gastrointestinal stromal tumors Sunitinib and regofinib are multi-target drugs It is worth mentioning that apatinib is a small molecule VEGF receptor inhibitor independently developed in China In addition to regofinib, three other molecular targeted drugs are on the market in China In 2015, there were 466100 cases of liver cancer and 422000 deaths in China Most liver cancer is asymptomatic in the early stage, and most patients are in the middle and late stage when they are diagnosed, so the prognosis is very poor For the treatment of liver cancer, surgical resection is the most fundamental method, but for the patients who can not be resected, especially with extrahepatic metastasis, there are few effective methods, and clinical treatment is very difficult Sorafenib is the first and only molecular targeted drug approved by many countries for the treatment of primary liver cancer At present, China has imported Colorectal cancer in China in 2015, the number of colorectal cancer patients was about 376300, and the death toll was about 191000 At present, the only molecular targeted drug for colorectal cancer is regofinib Regofinib is a multi-target drug, and its indications include gastrointestinal stromal tumor At present, the drug has not been listed in China, and the molecular targeted drug for colorectal cancer is still in the blank Breast cancer in 2015, the number of breast cancer patients in China was about 272400, and the death toll was about 70700 At present, the drugs for molecular targeted therapy of breast cancer include lapatinib targeting human epidermal growth factor receptor 2 (HER2), everolimus targeting rapamycin (mTOR), and pabosinib, the world's first CDK4 / 6 kinase inhibitor, which was just launched in 2015 The first two drugs have been imported and listed in China, while the latter has not yet been listed in China Pancreatic cancer: in 2015, the incidence of pancreatic cancer in China was about 90100, and the death toll was about 79400 Although gemcitabine based chemotherapy is the standard chemotherapy, the overall prognosis is still very poor and there are few long-term survivors At present, there are three approved molecular targeted drugs for the treatment of pancreatic cancer, all of which have been imported and listed in China Thyroid cancer thyroid cancer is the most common malignant tumor of endocrine system Most thyroid cancer can be cured by operation, I 131 internal radiation and thyroid stimulating hormone inhibition However, there is still a lack of effective treatment methods for advanced medullary cancer and local late stage radioiodine refractory thyroid cancer The use of molecular targeted drugs for these patients is a great progress in the treatment of thyroid cancer in recent years, and shows a good prospect Among them, sorafenib and lovatinib are used to treat differentiated thyroid cancer, while vandetanib and cabotinib are used to treat medullary thyroid cancer, with different indications At present, only solafeni is imported into China Although incidence rate of hematological malignancies is not high, there are still more molecular targeted drugs for leukemia Currently, FDA has approved 8 molecular targeted drugs In 2014, BCR was the target of all varieties In 2014, two varieties were listed, among which irutini is a small molecule Btk inhibitor, and idellisib is the first oral, selective phosphoinositide 3-kinase Delta (PI3K Delta, P110 delta) inhibitor This year's (2016) latest venetoclax is targeted at bcl-2 At present, only three kinds of leukemia molecular targeted drugs are on the market in China Another hematological tumor is lymphoma, which, like leukemia, is a multiple tumor in children Currently, the FDA has approved six molecular targeted drugs for lymphoma Among them, bortezomib was initially approved for the treatment of multiple myeloma In 2006, bortezomib was approved for the treatment of recurrent or refractory mantle cell lymphoma In 2014, bortezomib was approved for the treatment of previously untreated mantle cell lymphoma (MCL) patients, expanding the scope of application of the drug Bortezomib is the first drug approved in the United States for patients with previously untreated MCL In addition, in 2014, FDA approved three molecular targeted drugs for lymphoma, namely, elutinib, beliasta and idelalisib However, of the six drugs, only bortezomib is listed in China Radical nephrectomy is still the main treatment for renal cancer, but about one-third of renal cancer patients have metastasis at the initial diagnosis or local recurrence or distant metastasis after radical surgery Metastatic renal cancer is not sensitive to radiotherapy and chemotherapy, and its prognosis is poor The approval of targeted drugs is the dawn of renal cancer patients Sorafenib is the first molecular targeted drug approved by FDA for the treatment of renal cancer, and six varieties have been approved successively since then Pazopanil can be used not only in the treatment of renal cancer, but also in the treatment of advanced soft tissue sarcoma At present, sorafenib, sunitinib, Everest and acitinib are approved for import in China Molecular targeted drugs for other cancers (including multiple myeloma, melanoma, basal cell carcinoma and ovarian cancer) will not be described here In addition, there are two kinds of TiNi drugs that are not used for tumor, namely, tofetinib for rheumatoid arthritis and rousotinib for myelofibrosis Among these drugs, only bortezomib, which is used to treat multiple bone marrow, has been imported into the market in China, while others have not Multiple myeloma melanoma basal cell carcinoma and ovarian cancer Other conclusions, incidence rate and mortality rate of cancer in China has been increasing, and the number of patients has exceeded 100 million Molecular targeted drugs for cancer treatment, which have little damage to normal cells and specificity, are hot spots in the research and development of anti-tumor drugs Although there are many molecular targeted drugs on the market in the world, there are only 13 in our country, so it is difficult to meet the needs of patients The incidence rate of liver cancer, colorectal cancer, breast cancer, etc., the selectable molecular targeted drugs are few, especially for the treatment of liver cancer only 1 Therefore, the research and development of molecular targeted drugs is in the ascendant, and there are many fields waiting for us to explore.