What Is Targeted Therapy?
Targeted therapy is a method of treatment at the molecular level of a cancer site that has been identified.
- Chinese name
- Targeted therapy
- Pin pair
- Identified carcinogenic sites
- Also known as
- "Biological Missile"
- Level
- Cell molecule
- Related terms
- CLS DC-CIK cell targeted therapy
- Targeted therapy is a method of treatment at the molecular level of a cancer site that has been identified.
- Corresponding therapeutic drugs can be designed. When the drug enters the body, it will specifically select carcinogenic sites to combine and work, so that tumor cells will die specifically without affecting the normal tissue cells around the tumor. Therefore, molecular targeted therapy is also called "Biological Missile."
Introduction to Targeted Therapy
- In addition to conventional surgery, radiotherapy, chemotherapy, biological therapy and traditional Chinese medicine treatment, according to the target of tumors at the level of organs, tissues and molecules, different targeted treatment technologies can be used for target treatment. Local lesion targets can be treated with local targeted ablation therapy, targeted radiotherapy, radioactive particle implantation targeted internal irradiation therapy, high-energy focused ultrasound therapy, intravascular interventional therapy, and local drug injection therapy. The target of molecular targeted therapy is malignant phenotypic molecules targeting tumor cells, which act on specific cell receptors that promote tumor growth, survival, signal transduction and other channels, and regulate the formation of new blood vessels and the cell cycle to suppress tumor cell growth. Or promote the anti-tumor effect of apoptosis. Different from traditional cytotoxic chemotherapy, tumor molecular targeted therapy has specific antitumor effect, and the toxicity is significantly reduced, which has opened up a new field of tumor chemotherapy.
Targeted therapy related research
- With the development of society and technology, the concept of cancer treatment is undergoing a fundamental change, that is, from empirical science to evidence-based medicine, and from a cell attack mode to a targeted treatment mode. "Targeted therapy" that uses targeted technology to accurately deliver drugs to tumor areas and "target therapy" that uses tumor-specific signal transduction or specific metabolic pathway control are hotspots in tumor research.
- According to different target sites, tumor targeted therapy can be divided into two categories, namely tumor cell targeted therapy and tumor blood vessel targeted therapy. Targeted tumor cell therapy uses specific antigens or receptors on the surface of tumor cells as targets, while targeted tumor blood vessel therapy uses specific antigens or receptors on the surface of neonatal capillary endothelial cells in the tumor area. Although the targeting properties of monoclonal antibodies against tumor cells have increased the concentration in local tumor tissues to some extent, these macromolecules still need to pass through the vascular endothelial cell barrier to reach the target area of tumor cells. The process is relatively slow. Vascular targeting drugs have a great advantage, and they can accumulate at the target site quickly and in high concentration after administration.
Targeted therapy treatment
- 1. Argon-helium superconducting surgical treatment system (cryocareTM targeted cryoablation therapy, also known as argon-helium knife)
- Argon-helium knife is a widely used ablation treatment technology. Since 1998, there have been more than 100 hospitals in the United States, and more than 80 units in China have been equipped with argon-helium knife equipment, which can accurately freeze a variety of tumors. Resection, and made breakthroughs in the treatment of liver cancer, lung cancer, pancreatic cancer, prostate cancer, kidney tumors, breast cancer and other treatment areas. Intraoperative freezing is suitable for almost all parenchymal tumors. Unlike other ablation methods such as radiofrequency, argon-helium knife freezing can treat both small tumors and larger tumors (greater than 5cm in diameter) and a large number of tumors; due to blood vessels The heat release effect of the internal blood flow makes freezing difficult to cause damage to large blood vessels, so that it can also treat tumors near large blood vessels that cannot be surgically removed. According to the statistics of the 14th World Congress of Cryotherapy in November 2007, the number of tumors treated with CryocareTM argon-helium cryotherapy in China has reached 11,000 in China, of which more than 10 have completed more than 500 units, and some hospitals have reached 4,000. There are more than 30 kinds of diseases. China is the country that treats liver cancer and lung cancer the most in the world.
- Due to the different characteristics of various targeted ablation technologies, the choice of treatment technology for specific cases may be different. Domestic Dr. Zhang Keqin [4] compared argon-helium cryoablation with radiofrequency (RFA) and microwave (MCT) thermal coagulation for the comparison of rabbit VX2 liver cancer. Three minimally invasive treatments were used to ablate rabbit VX2 liver cancer, both in the ablation target. In terms of area area and transverse diameter, ablation target tumor complete ablation rate, or in terms of ablation target tumor cell residual rate and ablation target tumor cell necrosis rate, argon-helium knife freezing is better than RFA and MCT, and RFA and MCT are equivalent. In addition, the tumor boiling spread caused by the "boiling effect" of RFA and MCT is a clinically insurmountable problem, all these aspects suggest that the clinical efficacy of argon-helium knife freezing in the treatment of rabbit VX2 liver cancer may be better than RFA and MCT.
- Clinical treatment has confirmed that the combination of argon-helium knife local ablation and radiotherapy, chemotherapy, biological therapy, interventional therapy and other comprehensive treatments, the efficacy is better than single treatment, and the 1- to 2-year survival rate is significantly improved. Its long-term efficacy depends on comprehensive treatment measures. select. When the mass is 4cm, especially larger than 6cm, the treatment effect is poor, and the tumor is easy to recur and even grow. Therefore, the application of comprehensive treatment measures combined with other treatment methods before and after treatment is particularly important, for example, for the treatment of lung cancer: argon-helium knife combined with interventional chemotherapy, combined radiation therapy, combined with traditional Chinese medicine treatment, compared with radiation therapy, chemotherapy, and interventional embolism, 1 year The two-year survival rate has been significantly improved, and a satisfactory clinical effect has been achieved. The above results indicate that argon-helium knife will become an indispensable technology for clinical treatment of lung cancer. For tumors close to the mediastinum, local argon-helium knives can be completely ablated.After argon-helium knives can be combined with other local treatment methods, combined with radiotherapy can greatly reduce the radiation dose.Combined drug implantation and radiation particle implantation can Improving the efficacy and reducing the dose of implanted particles, combined with other local and systemic treatment techniques, can change the current concept of comprehensive treatment and improve the long-term treatment effect. At present, the domestic argon-helium knife treatment is in the ascendant, but there is no prospective, multi-center, randomized controlled clinical trial results to observe its long-term effect on the treatment of lung cancer.
- The argon-helium targeted therapy technology collaboration group has carried out more work, such as writing the world's first standardized treatment book, including animal and human solid tumor lesion ablation target area sizes, and frozen imaging changes. It is suggested that other targeted ablation techniques can be emulated.
- 2. Radio frequency ablation (RFA) and microwave ablation (MWA)
- Both MWA and RFA technologies started in the early 1990s. In 1996, LeVeen umbrella-shaped multi-electrode was approved by the US FDA, which greatly expanded the application scope of RFA. Compared with other thermal ablation technologies, RFA has been used worldwide so far. With more than one technology, more than 500 reviews can be retrieved. MWA is mainly carried out in Japan and China, and the majority of RFA reports come from European and American countries. It can be considered that the treatment effects of MWA and RFA technology are basically the same. The development of radio frequency electrodes from the original unipolar to multipolar, and the cold cycle radio frequency treatment system, the shortcomings are that the scope of one-time destruction of lesions is limited, the maximum destruction volume is 3.5cm in diameter, and cancerous tumors with a diameter of more than 3cm are liable to remain lesions. The American RITA company has developed a series of radiofrequency needles for tumors of different sizes. For tumors less than 3cm in diameter, the first generation of umbrella-shaped multipolar needles or monopolar needles can be selected; for tumors with diameters of 3cm to 5cm, second-generation anchored multipolar needles should be selected ; For tumors with a diameter of 5cm to more than 7cm, the latest third-generation cluster electrode needle should be selected, and a special syringe pump should be used to make the heat conduction faster and more uniform, the treatment time is greatly shortened, the effect of treating large tumors is more accurate, and the patient is easier.
- Some scholars have raised the question of how to combine radiofrequency therapy with chemotherapy and local radiotherapy to improve the efficacy in the treatment of advanced non-small cell lung cancer. For advanced non-small cell lung cancer, especially peripheral lung cancer, radiofrequency ablation is used first to inactivate cancer cells in the mass in a large area, reduce tumor burden, and then treat the remaining metastatic cancer cells with chemotherapy. For patients with hilar, mediastinal lymph nodes, or other metastatic lesions, radiotherapy and other treatments can be combined with chemotherapy. In this way, on the basis of local control of the tumor, the quality of life and survival time of patients are further improved. With the continuous improvement of RFA technology, the organic combination of RFA with interventional chemotherapy, stereotactic radiation therapy, and external irradiation will greatly improve the local control rate of tumors, improve the quality of life, and extend the survival time of patients.
- 3. Interstitial laser therapy (ILT) and photodynamic
- Laser ablation therapy (ILT) is a high-energy light beam with optical or near infrared wavelengths scattered in the tissue and converted into heat. The time is usually longer than RFA and can exceed 1 hour. The ablation range of laser tubes produced at home and abroad is relatively small, which is in clinical exploration and has not entered clinical use. The experimental study of composite probes attempts to expand the range of ablation.
- 4. High-intensity focused ultrasound ablation (HIFU)
- HIFU is the first of its kind in China. Currently, there are 4-5 manufacturers. For probe design, the frequency varies. HIFU can be used to treat many benign and malignant tumors, such as uterine fibroids, breast cancer, bone and soft tissue tumors. There have been successive clinical reports of the application of HIFU in the treatment of advanced pancreatic cancer in China. The curative effect shown is mainly analgesic and tumor volume changes after adjuvant radiotherapy and chemotherapy. This may be the effect of ultrasound hyperthermia, not the true HIFU ablation treatment. Domestic literature shows that HLFU has an inactivating effect on a variety of solid tumors such as primary and metastatic liver cancer. However, there are still many limitations in the application of HIFU to treat liver cancer. For example, although some ultrasound can enter the liver tissue through the intercostal space, the rib reflection makes the energy of the ultrasound to reach the target area greatly reduced; the long treatment time increases the risk of anesthesia in HIFU treatment. ; Skin burns caused by HIFU treatment limit the increase of its therapeutic dose; HIFU treatment increases the chance of liver damage while destroying liver cancer tissue. Therefore, how to improve the biological effect of ultrasound and reduce the treatment time of HIFU has become one of the keys to the success of this treatment.
- 5. Precision targeted external radiation therapy technology
- (1) x-knife, r-knife, 3D-CRT, IMRT
- Radiation therapy technology has made a qualitative leap at the end of the 20th century, mainly reflected in stereotactic radiosurgery (SRS), stereotactic radiotherapy (SRT), three-dimensional conformal radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) technology. The clinical application of this method has fundamentally changed the role and status of radiotherapy in tumor treatment in the past century. In the process of introducing the Swedish head r-knife, European and American x-knife, and the clinical application of 3D conformal radiation therapy, China has created a new situation of head and body r (x) -knife in Chinese model. The clinical application of this technology is relatively extensive, and has achieved good results, and has received high attention from colleagues at home and abroad.
- The x-knife was widely used in China in the late 1990s, with many cases being treated, but the long-term clinical results of large cases were lacking. After 2000, with the emergence of technologies such as three-dimensional conformal radiotherapy and intensity-modulated radiotherapy, especially China's whole body r -The advent of the knife has affected the clinical application and development of this technology in China, and the number of hospitals and treated cases has gradually decreased. However, there is no doubt that x-ray stereotactic radiotherapy technology is a unique dose focusing method. Obtaining a highly concentrated dose distribution can achieve a higher local control rate and lower radiation damage in the treatment of small tumors with parenchymal organs. Moreover, the emergence of new x-knife technologies such as Cyber Knife will play an important role in tumor treatment. The problems with the whole-body r-knife developed in China are that there are many models, insufficient software and hardware development, and insufficient resource integration, which makes each model fail to be perfect, especially in terms of dose evaluation and dose verification. There are serious deficiencies in the standardization of clinical applications, which have greatly affected the comprehensive and healthy development of this technology. Nevertheless, the unique dose focusing advantage of the whole body r-knife has been proven by a large number of clinical results. Therefore, strengthening this The clinical standardized application of technology, multi-center collaboration and experience accumulation, and further improvement of equipment are of great significance to promote the development of the radiotherapy equipment industry and the professional development of radiation oncology in China.
- (2) Image guided radiation therapy (IGRT) technology
- IGRT is 4D radiation therapy, and biological image-induced radiation therapy being developed, and so on. IGRT has developed rapidly in developed countries, such as Cyberknife, Tomotherapy, etc.
- CyberKnife (CyberKnife) is a new image-guided precise radiotherapy technology for tumors. It was developed by John Adler, a brain surgeon at Stanford University Medical Center in the United States, and Accuray. Its clinical application. It is a stereotactic therapy machine that integrates an image guidance system, a high-accuracy robot tracking and targeting system, and a radiation release irradiation system, which can complete the treatment of lesions in any part. A light linear electron accelerator capable of generating 6MV-X lines was placed on a 6-degree-of-freedom robotic arm, and the position of the target area was tracked by computing low-dose 3D images obtained by X-ray cameras and X-ray image processing systems. A treatment plan that "resects" the tumor with accurate doses of radiation. Because of its total clinical accuracy of sub-millimeter level, it is considered to be one of the most accurate stereotactic radiosurgery / treatment (SRS / SRT) technologies in the world. Compared with traditional SRS / SRT technology, Cyber knife has the advantages of real-time image guidance and frameless positioning. It has been approved by the US FDA for the treatment of intracranial tumors, extracranial tumors and benign tumors in 1999 and 2001. It has 8 years of clinical application history, and more than 40,000 patients worldwide have been treated with Cyberknife, especially In the treatment of intracranial tumors and spinal tumors, Cyberblade treatment has accumulated rich experience, but in the treatment of body tumors such as lung cancer, liver cancer, and abdominal tumors, it is still in a small sample, and the research phase of short-term follow-up. With the gradual popularization of Cyber Knife in China and the increase in the number of clinically treated diseases and cases, especially the development of complex conditions and the treatment of critically ill patients, patients with solid malignant tumors in the body undergo gold knife implantation in the tumor target area before Cyber Knife treatment. The complications of surgery need to be further summarized, so that the Cyber knife can be further standardized and rationally applied in our country, so that more cancer patients benefit from it. Cyber knives have certain advantages over conformal, intensity modulated, gamma knives, etc., and also provide the possibility of fractional high-dose radiotherapy, how to choose the best segmentation method and single dose, total dose, how to evaluate effective biological Dose and other issues have become urgent problems in the research. Under the existing conditions, combined with relevant knowledge of radiobiology, clinical medicine, etc., to optimize the treatment strategy and carry out comprehensive treatment including radiotherapy sensitization, chemotherapy, hyperthermia and even other radiotherapy methods to maximize the efficacy, then Is the main research direction in the future.
- Spiral tomography (Tomotherapy), invented by the University of Wisconsin-Madison, is an image-mediated three-dimensional intensity-modulated radiation therapy.It integrates a linear accelerator and a spiral to integrate the treatment plan, patient positioning and treatment process. As a whole, it can treat different target areas, from stereotactic treatment of small tumors to systemic treatments, all completed by a single spiral beam. Through the megavolt image obtained from each treatment, you can observe the tumor dose distribution and treatment. Changes in tumors during the process, timely adjustment of the target volume treatment plan. With the incomparable advantages of conventional accelerator radiotherapy, it has opened up a new treatment platform for radiation therapists and occupies an important position in the development history of intensity modulated radiation therapy.
- 7. Radioactive particles implanted in interstitial irradiation treatment
- The clinically used radioactive particles are mainly 125I and 103Pd, which represent low-dose rate and medium-dose rate radiation, respectively, and have their own characteristics in radiophysics and radiobiology. The process of implanting radioactive particles is required to be completed under the guidance of imaging. It meets the requirements of IGRT. Radioactive particles are implanted at one time to achieve the effect of a single dose of treatment.
- With the continuous improvement and improvement of the particle implantation treatment planning system, the dosimetry requirements have gradually become clear, the implantation treatment equipment has been continuously improved, and the clinical application of radioactive particles has continued to expand in the past 20 years, fully explaining the role and status of radioactive particles in clinical applications. Radiotherapy experts in Germany and Japan have acknowledged that the best indication for radioactive particles should be the case of the low-risk group of prostate cancer. Its long-term efficacy is similar to radical surgery or external irradiation, but the incidence of side effects, especially sexual dysfunction, is low. The treatment time is short, and the surgical method is simple and popular with patients. In terms of expanding the indications for radioactive particle therapy, radiation oncologists and surgical experts first use radioactive particles to treat non-small cell lung cancer. Chinese thoracic surgeons have achieved quite satisfactory results in the treatment of non-small cell lung cancer. Radioactive particle implantation for liver cancer (Primary liver cancer and metastatic liver cancer), pancreatic cancer, soft tissue sarcoma, bone tumor, early breast cancer, etc. have all obtained certain experience and efficacy in clinical trials. Endometrial particle implantation trials of cavity organ tumors at home and abroad, and domestic trials of stent carrying or bundling radioactive particles for implantation in cavity tumors (esophagus, bronchus) are all under development.
- The equipment of radioactive particles has been standardized, the most important of which is the treatment planning system (TPS), which must meet the requirements of quality verification. Radioactive particle implantation brachytherapy has developed rapidly in China. According to incomplete statistics, the country sells 20,000 to 30,000 125I particles per month and treats 4,000 to 6,000 patients. Such large-scale radiotherapy methods must be managed by rules and regulations. This work should be urgent. In addition, the clinical experience of radioactive particles should be carefully exchanged to make the clinical use of radioactive particles not only standardized, but also to continuously improve the efficacy. Reduce toxic side effects.
- 8. Endovascular interventional therapy and local drug injection
- Vascular interventional treatment of malignant tumors is performed by injecting antineoplastic drugs and / or embolic agents through a catheter into the nutritional artery of the tumor under the monitoring of X-ray equipment to treat tumor lesions. Due to the development of catheter instruments and imaging equipment, the contrast agent is continuously updated and increased, especially with the increase in the use of microcatheters, the accumulation of experience in the use of embolic agents, the continuous improvement of interventional techniques, and the selective infusion of superselective tumor blood supply arteries Perfusion chemotherapy and embolization have become routine clinical tasks. At the same time, the technology is less invasive and easy to operate, so it has developed rapidly, improving the effectiveness of this treatment method and prolonging the survival of cancer patients. Local drug injection treatment techniques, such as percutaneous alcohol injection of small liver cancer, percutaneous liver puncture injection of iodized oil plus chemotherapy drugs to treat liver tumors, and absolute alcohol, acetic acid, and hot saline injections for recurrence or residual lesions are routinely carried out in clinical practice, and the cost is Inexpensive and effective.
- Transcatheter or percutaneous intratumoral injection gene therapy has become a hot topic in tumor research, and some studies have entered animal experimental stages, for example, endothelin gene therapy via hepatic artery for liver cancer; adenovirus-mediated anti-K-ras ribosomal kinase Can inhibit the growth and induce apoptosis of pancreatic cancer cells; HSV-TK (herpes simplex virus thymidine kinase) -mediated gene therapy has been initially successful in animal models; drug-sensitive genes, apoptosis-regulating genes such as bcl -2, bax, survivin, and some genes that inhibit angiogenesis in tumors are all under extensive research. Recombinant human p53 adenovirus gene drugs have been used clinically by intradermal injection. Due to the relatively limited tumors of gene therapy, so far only liver cancer, pancreatic cancer, lung cancer, glioma, colorectal cancer, and laryngeal cancer can be treated with interventional gene therapy. Interventional gene therapy has been used in some tumors. The treatment has shown good efficacy, reduced adverse reactions, and brought great benefits to people. It is believed that with the deepening of research, intervention-oriented gene therapy will play a greater role in tumor treatment. More and more tumors will be cured.
- 9. Nerve Targeted Repair Therapy
- Nerve-targeted repair therapy allows nerve growth factors to act on the injury site through intervention. Activate dormant nerve cells, achieve self-differentiation and renewal of nerve cells, and replace damaged and dead nerve cells, rebuild neural circuits, increase brain oxygen supply and blood circulation, and promote the development of organs again. [1]
- 10. Photodynamic therapy
- Photodynamic targeted therapy [2] refers to the function or morphological change of organism cells or biomolecules under the action of light with the participation of photosensitizers, leading to cell damage and necrosis in severe cases, and this effect must be aerobic The method of photodynamic therapy is also called photodynamic therapy (PDT). Research on targeted drugs, that is, photosensitizers (photodynamic therapy drugs), is the key to affecting the prospects of photodynamic therapy. Photosensitizers are some special chemical substances. Their basic function is to transfer energy. They can be excited by absorbing photons, and quickly transfer the absorbed light energy to the molecules of another component, causing them to be excited and the photosensitizer itself to return. Ground state.
- Targeted therapy for diseases: condyloma acuminatum, acne, erythema nevus, tumors, etc.
- Therapeutic advantages:
- (1) Minimal trauma: With the help of fiber optics, endoscopes, and other interventional techniques, the laser can be guided deep into the body for treatment, avoiding the trauma and pain caused by open surgery and abdominal surgery. [3]
- (2) Low toxicity: Photosensitive drugs that enter tissues only reach a certain concentration and are irradiated with a sufficient amount of light to trigger a photodynamic reaction and kill targeted cells, which is a method of local treatment. The part of the human body that is not exposed to light does not produce this reaction. The organs and tissues in other parts of the human body are not damaged, and the hematopoietic function is not affected. Therefore, the toxic and side effects of photodynamic therapy are very low.
- (3) Good selectivity: The main target of the attack is the diseased tissue in the light area, which damages the normal tissues around the lesion slightly. This selective killing effect is difficult to achieve by many other treatment methods. [4]
- (4) Good applicability: It is effective for lesion tissues of different cell types and has a wide range of applications; while lesion tissues of different cell types can have large differences in sensitivity to radiotherapy and chemotherapy, and their applications are limited. [5]
Targeted therapy
- In recent years, with the development of molecular biology technology and the further understanding of the pathogenesis from the cellular and molecular level, the development of tumor targeted therapy has entered a new era. Progress in these areas has been rapid and good results have been achieved in the clinic. According to the targets and properties of the drugs, the drugs targeted for the main molecular therapy can be divided into the following categories:
- 1. Targeted epidermal growth factor receptor (EGFR) blockers, such as Gefitinib (Iressa, Iressa); Erlotinib (Tareva); ZD1839 (Iressa) can increase Antitumor effects of drugs such as PDD, CBP, Taxol, Docetaxel, and ADM, but do not increase the antitumor effect of Gemzar; OSI-774 (Tarceva, erlotinib) is also an epidermal growth factor receptor-tyrosine kinase (EGFR-TK ) Antagonist, is a small molecule compound. In September 2002, the US FDA approved its second-line or third-line treatment plan for advanced NSCLC that has failed as a standard regimen. OSI-774 is also effective for head and neck tumors and ovarian cancer; Phase III clinical trials of combined chemotherapy for pancreatic cancer are ongoing; Phase III of OSI-774 in combination with cisplatin + cisplatin for non-small cell lung cancer is underway Clinical trials; Phase III clinical trials of OSI-774 combined with Taxol + Carboplatin for non-small cell lung cancer have also been conducted in the United States; some clinical trials have preliminary results. Glivec (STI571, imatinib, Gleevec) is a tyrosine kinase inhibitor. It is a small molecule compound used in patients with chronic phase of CML who have failed previous interferon therapy. The effective rate is 100%. Leukemia (ALL) remission rate is as high as 70%. Glivec also shows that the disease control rate of gastrointestinal malignant stromal cell tumor (GIST) patients is 80% to 90%; malignant gliomas that are highly antagonistic to chemotherapy and radiotherapy ( (Most common brain tumor) may be effective.
- 2. Monoclonal antibodies against certain specific cell markers, such as Cetuximab (Erbitux); monoclonal antibodies against HER-2, such as Herceptin (Trastuzumab, Herceptin);
- Anti-EGFR monoclonal antibodies, such as C225 (Cetuximab, erbitux), improve the benefit rate of patients with colon cancer who fail 5-Fu and CPT-11 treatment. It is shown that as long as EGFR is blocked, the sensitivity to chemotherapy can be regained, and the use of EGFR inhibitors in the first-line combination may be more effective. Anti-Her-2 monoclonal antibody Herceptin has a significant anti-tumor effect in vitro at 3-100 mg / kg. Herceptin has a synergistic anticancer effect with doxorubicin and paclitaxel, while Herceptin has a more obvious synergistic effect with paclitaxel. Anti-CD20 antibody (mabthera, rituximab) has been approved for the treatment of low-grade malignant B-cell lymphoma, and is being explored in combination with chemotherapy for the treatment of high-grade lymphoma.
- 3. Tyrosine kinase receptor inhibitors, such as Crizotinib (Xalkori)
- Crizotinib (Secure®), a tyrosine kinase receptor inhibitor, targets molecules including ALK, hepatocyte growth factor receptor (HGFR, c-Met), and RON. The FDA has approved the treatment of non-small cell lung cancer (NSCLC) for anaplastic lymphoma kinase (ALK) gene rearrangement. Translocation can promote the expression of oncogenic fusion protein by ALK gene. The formation of ALK fusion proteins can cause the activation and deregulation of gene expression and signals, which in turn promote the proliferation and survival of tumor cells expressing these proteins. Crizotinib has a concentration-dependent inhibition of the phosphorylation of ALK and c-Met at the cellular level in tumor cell lines, and has xenograft-bearing tumors expressing EML4-ALK or NPM-ALK fusion protein or c-Met Mice have antitumor activity.
- 4. Anti-tumor angiogenesis drugs have been developed
- There are bevacizumab and endostatin endostatin. Bevacizumab (avastin, rhuMab-VEGF) is a recombinant human anti-VEGF ligand monoclonal antibody. Endostatin is an endogenous anti-angiogenic factor.
- The development and application of molecular targeted therapy drugs will have a huge impact on the original concepts and models of tumor therapy. However, although certain curative effects have been achieved, there are still many problems to be solved, such as the prediction of therapeutic effects. Foreseeable use in patients who may be effective can avoid unnecessary investment; how to cooperate with traditional treatment methods to achieve the purpose of improving efficacy; the problem of drug resistance of molecular targeted drugs and so on. It is believed that with the deepening of tumor molecular biology research, the mechanism of drug action will be further clarified, the individualization of drug application will become possible, and more cancer patients will benefit from it.
- 5. Bcr-Abl tyrosine kinase inhibitors, such as Imatinib and Dasatinib;
- 6. Vascular endothelial growth factor receptor inhibitors, such as Bevacizumab (Avastin);
- 7. Anti-CD20 monoclonal antibodies, such as Rituximab;
- 8. IGFR-1 kinase inhibitors, such as NVP-AEW541;
- 9. mTOR kinase inhibitors, such as CCI-779;
- 10 Ubiquitin-proteasome inhibitors, such as Bortezomib;
- 11. Others, such as Aurora kinase inhibitors, histone deacetylase (HDACs) inhibitors, etc.
- The following table is a targeted antitumor drug approved by the US Food and Drug Administration (FDA): [3]
- Table 1 FDA-approved monoclonal antibodies
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(Mabthera) Rituximab |
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(Herceptin) Trastuzumab (Herceptin) |
(ERBB2 / neu) |
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(Avastin) Bevacizumab (Avidin) |
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(Erbitux) Cetuximab (Ebitux) |
(HER1 / ERBB1) |
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(Vectibix) Panitumumab (Vectipib) |
(HER1 / ERBB1) |
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(Yervoy) |
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(Gazyva) |
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emtansine (Kadcyla) / T-DM1 |
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(Cyramza) |
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- Table 2 FDA-approved small molecule targeted antitumor drugs
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(Gleevec) Imatinib (Gleevec) |
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(Iressa) Gefitinib (Iresa) |
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Erlotinib (Trokai) |
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(Xalkori) Crizotinib (Secori) |
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(Bosulif) Bosutinib |
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Cabottini |
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(Inlyta) Axitinib |
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(Sprycel) Dasatinib (Starsay) |
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(Nexavar) Sorafenib (Dogeme) |
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(Sutent) Sunitinib (Sortan) |
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(Tykerb) Lapatinib (Terissa) |
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(Tasigna) Nilotinib (Dahina) |
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Tisirolimus |
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Everolimus (finite) |
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(Votrient) Pazopanib |
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(Iclusig) |
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Regogini |
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(Jakafi) |
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(Xeljanz) Tofatinib |
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Van der Thani |
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Verofini |
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(Tafinlar) Darafeni |
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(Mekinist) Trimetinib |
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(Gilotrif) Afatinib |
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(Imbruvica) Ibrutinib |
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