What Is Involved in Laser Cancer Treatment?
Targeted therapy is to design a corresponding therapeutic drug at the level of cellular molecules, targeting a well-defined oncogenic site (this site can be a protein molecule inside a tumor cell or a gene fragment), and the drug enters the body It will specifically select the carcinogenic site to combine and work to cause tumor cells to specifically die without affecting the normal tissue cells around the tumor. Therefore, molecular targeted therapy is also called "bio-missile".
Targeted Therapy for Cancer
- Tumor-targeted therapy technology refers to targeting tumors under non-invasive or minimally invasive conditions, using local or systemic treatments that are selective, highly targeted, easy for patients to accept, and have a small response. A general term for various means for the purpose of tissue damage. At present, tumor-targeted therapy has become more and more important in tumor therapy due to its specificity and targeting, and has become the main direction of tumor therapy.
- Tumor-targeted therapy technology can be divided into three categories: biological targeted therapy, chemical targeted therapy, and physical targeted therapy.
- With the continuous improvement of modern science and technology, people's understanding of tumors has penetrated into cells, molecules and
Targeted Therapy for Cancer
- Among biological targeted therapies, the more mature is adoptive cellular immunotherapy. The concept of this therapy is to treat tumors with the principle of "killing tumor cells with the body's own immune cells". While using cells with tumor-killing activity to treat tumors, it can enhance the body's immune function and inhibit the growth of tumor cells. .
- Adoptive immune effector cell therapy has attracted people's attention because it has the following advantages, and has been a very active research area in tumor immunotherapy for more than a decade:
- 1. Immune cells can be processed in vitro to bypass the various mechanisms of tumor immune disorders in the body, thereby selectively exerting anti-tumor immune responses. For example, freshly isolated tumor infiltrating lymphocytes (TIL) often lack antitumor effects, and specific antitumor effects can be restored after incubation for a period of time under certain conditions in vitro. In vitro culture conditions, tumor antigen specific Tolerant immune cells can be reversed.
- 2. The activation and effector processes of immune cells are often mediated by some cytokines. At present, genetic engineering can clone a large number of different cytokines, and also a large number of tumor antigens or peptides, which enables in vitro activation to expand a large number of anti-tumor immune cells. More feasible and convenient.
- 3. The in vitro activation and expansion of immune cells can avoid serious toxic and side effects caused by the large-scale application of some preparations in vivo, such as: IL-2, TNF-, IL-4, IL-7, IL-12, etc. have anti-tumor effects, The in vivo application of anti-CD3 monoclonal antibodies (MabCD3) can activate T lymphocytes, but due to their complex and multiple effects, a large number of applications in the body can cause serious or even lethal side effects, which is also difficult for these factors to be approved for clinical use These are important reasons to avoid these side effects while operating in vitro.
- 4. A large number of autologous or allogeneic anti-tumor immune cells have been expanded in vitro. The number is greater than the number of effector cells activated by tumor vaccines in the body. Some in vitro cultured immune cells have entered clinical treatment trials. Experiments show that the application of tumor vaccines in vivo can increase the number of tumor-specific CTLs in the body, but at a certain time, CTLs in the body reach the plateau phase and no longer increase. This is mainly limited by the presence of specific and non-specific immune regulatory networks in the body. Clonal expansion. In vitro culture can break through this regulatory network and amplify a large number of immune effector cells.
- The technology has undergone stages such as LAK cell therapy, TIL cell therapy, CIK cell therapy, DC-CIK cell therapy, and EAAL cell therapy, and its clinical efficacy and specificity have gradually improved.
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- The basis of tumor biological targeted therapy is that the body's immune system has the ability to monitor and kill tumor cells. Compared with traditional chemotherapy and radiation therapy, biological targeted therapy has the characteristics of high specificity and small side effects. Theoretically, every tumor patient can benefit from biological targeted therapy, and since the early stage of the patient's immune system has not been seriously affected by the tumor, the response to biological targeted therapy is better, and the efficacy will be relatively strengthen. At present, the target of biological targeted therapy is often patients who cannot perform other treatments in the late stage. Even in these patient groups, the efficacy shown by biological targeted therapy is enough to make it the fourth tumor treatment method after surgery, radiotherapy and chemotherapy.
- EAAL is the abbreviation of Expanding Activated Autologous Lymphocytes in English. EAAL cell technology is one of the biological targeted treatment methods for treating malignant tumors and chronic infectious viral infections. Its technology is to isolate mononuclear cells from patients' peripheral blood (20-100 ml), and expand and culture in vitro to stimulate the cell subpopulations that have the killing effect of killing tumor cells and virus infected cells under physiological conditions. CD8 + killer T lymphocytes (CTL, about 70%) and natural killer cells (NK, about 20%) were extensively expanded and activated, and then returned to the patient one or more times. As a cell adoptive immunotherapy method, it can effectively treat malignant tumors and chronic infectious viral infections.
- The main effector cells of EAAL therapy are: CD3 + CD8 + cells
- The effector cells containing tumor antigen specific recognition and killing can directly and specifically kill tumors. Under some conditions, it can also destroy tumor stroma and inhibit tumor angiogenesis.
- NK cells can directly kill tumor cells. They are non-MHC restricted. They are activated by recognizing NK receptors on the surface of tumor cells, and they exert antitumor effects by releasing killer effector molecules.
Targeted cancer therapy
- That is, molecular targeted drug therapy. The development of oncology in the past 50 years in drug development has focused on cytotoxic aggressive drugs. Although following anthracyclines (adriamycin, epirubicin) and platinum (cisplatin, carboplatin), there are many powerful chemotherapeutics such as Taxol, Texotele, Capetop, Platinum Oxalate, Health Echoselection came out and played an important role in different cancers, but its properties still belong to drugs that cannot distinguish between tumor cells and normal cells, and clinical applications are limited by many factors. When scientists continue to explore the molecular pathogenesis of cancer, they realize that if they can give a powerful blow to the specific molecular changes of cancer, they will greatly improve the treatment effect and trigger a change in the concept of anti-cancer treatment. In recent years, new molecular targeted drugs have achieved significant effects in clinical practice. Practice has shown the correctness and feasibility of molecular targeted therapy theory. The treatment of cancer has been pushed to an unprecedented stage.
- The reason why molecular targeted therapy has received close attention and attracted researchers' continuous exploration is that it takes the change of the characteristics of tumor cells as the target, while exerting stronger anti-tumor activity while reducing the toxicity to normal cells side effect. This targeted treatment method points a new direction for tumor treatment.
- 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. Small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as Gefitinib (Iressa, Iressa); Erlotinib (Tareva);
- 2. Anti-EGFR monoclonal antibodies, such as Cetuximab (Erbitux);
- 3. Anti-HER-2 monoclonal antibodies, such as Herceptin (Trastuzumab, Herceptin);
- 4. Bcr-Abl tyrosine kinase inhibitors, such as Imatinib;
- 5. Vascular endothelial growth factor receptor inhibitors, such as Bevacizumab (Avastin);
- 6. Anti-CD20 monoclonal antibodies, such as Rituximab;
- 7. IGFR-1 kinase inhibitor, such as NVP-AEW541;
- 8. mTOR kinase inhibitors, such as CCI-779;
- 9. Ubiquitin-proteasome inhibitors, such as Bortezomib;
- 10. Others, such as Aurora kinase inhibitors, histone deacetylase (HDACs) inhibitors, etc.
- After entering the 21st century, the anti-tumor drug research and development strategy is to gradually introduce the development of molecular targeted drugs while continuing to develop cytotoxic drugs. To date, many targeted drugs have played an extremely important or even miraculous role in the clinic. Some have entered standard treatment protocols and norms recognized by the international oncology community in accordance with the principles of evidence-based medicine. More and more promising drugs are also being developed in rapid development and early clinical trials. All of these give us reason to believe that the current drug treatment of tumors is in the transition period from pure cytotoxic attack to molecular targeted regulation, which should be promising.
- In order to achieve this goal, we need to know more about the molecular biology of targeted drugs and treatments; understand that most solid tumors have the characteristics of multi-target and multi-channel regulation; and that the current translational research is still far away. Failed to explain all the clinical phenomena that occurred; understand that different nationalities, genders, various environments and conditions may have different responses to treatment.
Targeted Therapy for Cancer Physical Targeted Therapy
- Cryotherapy
- A. 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.
- 2. Hyperthermia
- A. Radio frequency ablation (RFA)
- Radio frequency is a high-frequency vibration with a frequency of 150,000 times per second. The human body is a complex structure composed of many organic and inorganic substances. Body fluids contain a large number of dielectrics, such as ions, water, colloidal particles, etc. The human body mainly relies on ions to conduct electricity. Under the action of high-frequency alternating current, the direction of ion concentration changes back and forth with the positive and negative half cycles of the current direction. Under high-frequency oscillation, the ions between the two electrodes move rapidly along the direction of the power line, gradually changing from a moving state to a vibrating state. Due to the different sizes, masses, charges, and moving speeds of various ions, the ions rub against each other and collide with other particles to produce a biothermal effect. Due to the poor heat dissipation of the tumor, the temperature of the tumor tissue is higher than its adjacent normal tissue, and the cancer cells are sensitive to high heat, which can kill the cancer cells without side effects.
- B. Microwave ablation (MWA)
- Microwave ablation is similar in principle to radio frequency ablation. Microwaves can cause the molecular coupling of the target tissue to be oscillated and rotated to generate heat, resulting in thermal solidification. The main mechanism of tissue thermal denaturation is the rotation of water molecules. This rotation alternates with the ultra-high-speed microwave (2450MHz) electric field. Microwaves are emitted from the distal end of the electrode, resulting in a high-temperature region in the range of 2.0-3.0 cm, and a spindle-shaped solidified lesion can be formed in the cancerous tissue. In vivo, the conduction of microwaves does not need to depend on the conductivity of tissues, and is less affected by carbonization and dehydration of tissues.Therefore, MWA has a larger ablation range than RFA, and the temperature in the tumor is high enough, the ablation time is shorter, and the tumor is inactivated More completely. In addition, compared with radio frequency ablation, MWA is less affected by the cooling effect caused by blood perfusion, and can evenly inactivate tumor target areas near blood vessels. And multiple microwave energy sources can be applied at the same time without mutual interference during radio frequency ablation, so it can reach a larger ablation range in a short time.
- C. Interstitial laser therapy (ILT)
- Laser ablation (ILT) also destroys tumor lesions with thermal effects. This technology uses optical or near-infrared wavelengths of high-energy light beams to scatter into tissue to transform it into heat. The time is usually longer than RFA and can exceed 1 hour. At present, the ablation scope of laser tubes produced at home and abroad is relatively small, which is in clinical exploration and rarely used in clinical use.
- D. High-intensity focused ultrasoundablation (HIFU)
- High intensity focused ultrasound (HIFU) is a treatment technique that can focus the ultrasound beam to cause the target tissue to heat up and cause it to ablate without damaging surrounding healthy structures. HIFU can be used to treat many benign and malignant tumors, such as uterine fibroids, breast cancer, bone and soft tissue tumors.
- 3. Radionuclide therapy
- Precision Targeted External Radiation Therapy
- A. x-knife, -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.
- B. Image guided radiation therapy (IGRT) technology
- IGRT is 4D radiation therapy, and biological image-induced radiation therapy being developed, and so on. IGRT is currently developing 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.
- 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.
- C. 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. In recent years at home and abroad, endometrial particle implantation experiments have been performed on cavity tumors, and domestic trials of stent carrying or bundling radioactive particles into cavity tumors (esophagus, bronchus) have been under development.
- Photodynamic therapy
- Photodynamic therapy (PDT) is the product of the organic combination of laser, light guide, optical information processing, biophotochemistry and modern medicine. It is a kind of selective photochemical destruction of diseased cells using photosensitizers and lasers, and has a small impact on the surroundings. Technology, one of the main tumor suppressor mechanisms is the induction of tumor cell apoptosis, which can avoid multidrug resistance, and has the advantages of minimally invasive, targeted, broad-spectrum, repeatable, and flexible. As early as 4000 years ago in ancient Egypt, psoralen and ultraviolet radiation were found to treat white spots on the skin.
- In 1976, Kelly et al. Used hematoporphyrin derivatives to treat bladder tumors successfully, marking the beginning of modern clinical PDT. At the turn of the century, the photosensitizers Photofrin and Diomed semiconductor lasers were approved by the US FDA. More than 10 countries in Europe and Asia have also approved PDT for routine use in the treatment of esophageal, lung, bladder, cervical, and skin cancer. With the combination of PDT and imaging technology (especially interventional), its application scope has expanded to liver cancer, pancreatic cancer, bile duct cancer, and thoracic and abdominal cavity tumors.
- 5. Interventional Therapy
- 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. In the past 10 years, due to the development of catheter instruments and imaging equipment, the contrast agent has been 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 superselective tumor supply of arteries Targeted intubation 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.
- 6. Electrochemical technology
- Electrochemical treatment of diseases has a history of nearly 100 years. In 1983, Nordenstrom first proposed the theory of biological closed circuit and vascular interstitial closed circuit, and formulated a set of procedures for direct current treatment of tumors. In 1987, Xin Yuling took the lead in conducting basic and applied research on electrochemical therapy (ECT). ECT inserts a platinum electrode needle into the tumor tissue and connects it to a DC therapy device. Then the tissue undergoes electrolysis, electroosmosis, and electrochemical reactions, which changes and destroys the tumor microenvironment, and a series of biological effects that lead to cell death. ECT is suitable for body surface and visceral tumors, especially for malignant stenosis of anastomotic stoma after esophageal cancer surgery. Meningiomas and gliomas can also be used with caution.