Antitumor drugs are a class of drugs for the treatment of tumor diseases.In short, there are chemotherapy drugs and biological agents.In recent years, the development of molecular oncology and molecular pharmacology has gradually clarified the nature of tumor;The invention and application of large-scale rapid screening, combinatorial chemistry, genetic engineering and other advanced technologies have accelerated the process of drug development;The research and development of anti-tumor drugs has entered a new era.
Antitumor drugs are a class of drugs for the treatment of tumor diseases.In recent years, the development of molecular oncology and molecular pharmacology has gradually clarified the nature of tumor;The invention and application of large-scale rapid screening, combinatorial chemistry, genetic engineering and other advanced technologies have accelerated the process of drug development;The research and development of anti-tumor drugs has entered a new era.Today's development strategy of anti-tumor drugs includes the following points: (1) Take solid tumors accounting for more than 90% of malignant tumors as the main target;(2) Looking for active ingredients from natural products;(3) Find new molecular targets (enzymes, receptors, genes, etc.) for the mechanism of tumor occurrence and development;(4) High through put screening;(5) Introduction and application of new technologies: combinatorial chemistry, structural biology, computer-aided design, genetic engineering, DNA chip, pharmacogenomics (combination of functional genomics and pharmacology), etc.[1]
2、 R&D background
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According to the statistics of the World Health Organization (WHO), 3/5 of the world's people die of cancer, diabetes, cardiovascular diseases and chronic respiratory diseases, and cancer is one of the most important causes of death.In 2008, 7.6 million people died of cancer worldwide, accounting for 13% of the global death toll. More than 70% of cancer deaths occurred in low - and middle-income countries.
The results of the third national survey on causes of death by the Ministry of Health show that cancer is the second leading cause of death in China after cardiovascular and cerebrovascular diseases, accounting for 22.32% of the total number of deaths, and has become the first cause of death in Chinese cities, accounting for 1/4 of the number of urban deaths in China.China's cancer mortality rate is close to that of the United States, Britain and France, but higher than that of Asian countries (such as Japan, India and Thailand).From the perspective of different causes of cancer death, the mortality rate of lung cancer, colorectal cancer, pancreatic cancer and breast cancer in cities is significantly higher than that in rural areas;However, liver cancer, gastric cancer, esophageal cancer and cervical cancer are higher in rural areas.
At present, drug therapy has become one of the important means of clinical treatment of cancer. Affected by the high incidence and mortality of cancer, the sales of anti-tumor drugs have also increased year by year[2-3]。
3、 Drug classification
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At present, there are about 80 kinds of common anti-tumor drugs in the world, which can be roughly divided into the following six categories: cytotoxic drugs, hormone drugs, biological response regulators, monoclonal antibody drugs, other drugs, and adjuvant drugs[4]。
1. Cytotoxic drugs
(1) Drugs acting on the chemical structure of DNA
① Alkylating agents and nitrogen mustard (such as nitrogen mustard, phenylbutyrate nitrogen mustard, cyclophosphamide, ifosfamide, mephalan, etc.), cetipa (such as cetipa, etc.), nitrosamines (such as carmustine, smeristine, etc.) and methyl sulfonates (such as busulfan, etc.)
② Platinum compounds (such as cisplatin, carboplatin and oxaliplatin)
③ Mitomycin (such as mitomycin)
(2) Drugs affecting nucleic acid synthesis
① Dihydrofolate reductase inhibitors (such as methotrexate, pemetrexed, etc.)
② Thymosine synthase inhibitor (such as 5-FU, FT-207, capecitabine, etc.)
③ Purine nucleotide synthase inhibitor (such as 6-mercaptopurine, 6-TG, etc.)
④ Nucleotide reductase inhibitors (such as hydroxyurea)
⑤ DNA polymerase inhibitor (such as cytarabine, gemcitabine, etc.)
(3) Drugs acting on nucleic acid transcription
Drugs that selectively act on the DNA template and inhibit DNA dependent RNA polymerase, thereby inhibiting RNA synthesis (such as actinomycin D, daunorubicin, doxorubicin, epirubicin, aclamycin, and corynebacterium)
(4) Topoisomerase I inhibitors acting on DNA replication (such as irinotecan, topotecan, hydroxycamptothecin, etc.)
(5) Drugs that mainly interfere with tubulin synthesis during mitotic M phase (such as paclitaxel, docetaxel, vinblastine, norvinblastine, podophylloids, homoharringtonine, etc.)
(6) Other cell poisons (such as asparaginase)
2. Hormone drugs
(1) Anti estrogen (such as tamoxifen, toremifen, exemestane, etc.)
(2) Aromatase inhibitors (such as aminophenetidine, formestane, letrozole, anastrozole, etc.)
(3) Progesterone (such as medroxyprogesterone, megestrol, etc.)
(4) Sex hormone (such as methyl testosterone, testosterone propionate, diethylstilbestrol, etc.)
(5) Anti androgen (such as flutamide)
(6) RH-LH agonists/antagonists (such as goserelin, leuprorelin acetate, etc.)
3. Biological reaction regulator
Suppress tumor mainly through body immune function
(1) Interferon
(2) Interleukin-2
(3) Thymic peptides
4. Monoclonal antibody drugs (such as rituximab injection, trastuzumab for injection, bevacizumab, etc.)
5. Other drugs
Including some drugs with unknown mechanism and to be further studied
(1) Cell differentiation inducer (such as retinoids, arsenite, etc.)
After years of development, many important advances have been made in the research and development of anti-tumor drugs.However, facing the most serious threat to human life and health and accounting for more than 90% of malignant tumors, solid tumors still lack highly effective and specific drugs, which on the one hand reflects the difficulty in the research and development of anti-tumor drugs, on the other hand, it also means that the research and development of anti-tumor drugs also requires the use of new ideas, new technologies and new methods.
The progress of anti-tumor drugs caters to the requirements of anti-tumor drug research and development, lays the foundation for individualized treatment, and indicates a new era of anti-tumor drug research and development: molecular targeted drugs have improved the efficacy of some chemotherapy resistant tumors, and also have certain advantages in tolerance. The combination with chemotherapy, radiotherapy, and targeted drugs is expected to further improve the efficacy.This research concept has penetrated into all fields of anti-tumor drug development worldwide, laying the foundation for providing highly selective, efficient and low toxic drugs.At the same time, the research of biomarkers has been paid more and more attention, which not only contributes to the therapeutic application of anti-tumor drugs, but also promotes the in-depth research and development of anti-tumor drugs.In addition, the development of new therapeutic drugs such as anti-tumor vaccines has further enriched the therapeutic means.On this basis, with the development of chip technology and bioinformatics technology, tumor cells can be accurately classified (molecular typing) at the level of gene structure and expression. It has become possible to guide individualized targeted therapy, which will maximize the anti-tumor efficacy of molecular targeted drugs in combination with other drugs[5]。
