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What is Molecular Targeted Therapy?

   As the name implies, molecular targeted therapy is to target specific targets on tumor cells for treatment. It is a therapeutic modality targeting already defined carcinogenic sites at the cellular and molecular level. According to the driver gene is the main cause of cancer, the researchers designed the corresponding treatment drugs. When these drugs enter the body, they will specifically select oncogenic sites to combine and act, causing specific death of tumor cells without affecting the normal tissue cells around the tumor. Therefore, molecular targeted therapy is also called "biological missiles".

  Compared with the traditional "enemy or foe" chemotherapy, molecular targeted therapy is more precise. If chemotherapy is compared to a traditional weapon for "bombing" tumor cells, then molecular targeted therapy is a new generation of "precision-guided" weapons at the molecular gene level. Although it cannot completely cure tumors, it can effectively prolong the survival time of patients, and it does less damage to normal cells and has fewer side effects than chemotherapy, and can further improve the quality of life of patients with advanced tumors.

What are the commonly used molecular targeted drugs


  Most of the drugs used in molecular targeted therapy are small molecule drugs or monoclonal antibodies. Small molecule drugs can enter the interior of cells, so they often act on intracellular targets. Monoclonal antibodies are drugs that cannot easily enter cells, so they can only target targets on the surface of tumor cells. At present, the commonly used molecular targeted drugs are as follows.

  1. Epidermal growth factor receptor inhibitors. Such as tyrosine kinase inhibitor (EGFR-TKI) gefitinib, erlotinib, erlotinib, osimertinib, almetinib, vometinib for epidermal growth factor receptor-positive lung adenocarcinoma Tini et al. Anti-EGFR monoclonal antibodies, such as cetuximab, can be used for colorectal cancer, head and neck squamous cell carcinoma. For lung cancer ALK gene fusion mutation targeted drugs, crizotinib, ceritinib, ensatinib, alectinib, brigatinib, etc.

  2. Antiangiogenic drugs. Small molecule multi-target anti-angiogenic drugs, such as anlotinib, lenvatinib, apatinib, and regorafenib, are widely used in the treatment of lung cancer, gastric cancer, liver cancer and other malignant tumors. Macromolecular anti-angiogenic drugs, such as bevacizumab, are a recombinant monoclonal antibody against vascular endothelial growth factor (VEGF), which inhibits the formation of tumor angiogenesis by blocking the binding of VEGF to its receptors. Invasion of tumors into the vasculature and proliferation of metastases can achieve the purpose of treating lung cancer, colorectal cancer and ovarian cancer.

  3. Anti-HER-2 drugs. Anti-HER-2 monoclonal antibodies, such as trastuzumab and inituzumab; Monoclonal antibody, Desi trastuzumab (DS-8201 or T-DXd), etc. They currently have an excellent "record" in common solid tumors such as non-small cell lung cancer, breast cancer, gastric cancer, and colorectal cancer.

  4. BTK inhibitors. It is a key kinase in the B cell receptor signal transduction pathway, widely expressed in different types of hematological malignancies, and is involved in the proliferation, differentiation and apoptosis of B cells. Due to the very good specificity of BTK small molecule inhibitors, it has shown very good advantages in the treatment of B-cell malignant tumors and some B-cell immune diseases. Such as ibrutinib, zanubrutinib, and orelabrutinib.

  5. Multi-targeted kinase inhibitors. Such as sorafenib, sunitinib, pazopanib, lapatinib, etc., which can be used for the treatment of malignant tumors such as liver cancer and kidney cancer.

  6. Bcr-Abl tyrosine kinase inhibitors. Such as imatinib, can be used for the treatment of chronic leukemia and gastrointestinal stromal tumor.

  7. mTOR kinase inhibitor. Such as everolimus, can be used for the treatment of malignant tumors such as kidney cancer.

  8. Anti-CD20 monoclonal antibody. Such as rituximab, for the treatment of lymphoma.

  There are many molecular targeted therapies for various malignant tumors, but they are still in the clinical exploration stage.

How to choose molecular targeted therapy


  Molecular targeted therapy of tumors is a major breakthrough in medicine. According to the different targets of cancer cells at the cellular and molecular levels, the corresponding therapeutic drugs are selected. After the drug enters the body, it specifically selects the cancer-causing site, allowing cancer cells to die specifically, without affecting normal tissues and cells. Molecular targeted therapy has significantly reduced toxicity, opening up a new field of cancer chemotherapy. Molecularly targeted drugs cannot cure all diseases, nor can they replace traditional tumor treatment methods. Not all tumor patients are suitable for molecularly targeted drug therapy or need to receive molecularly targeted therapy.

  Before using molecular targeted therapy drugs, the corresponding genes must be detected, and patients must have a clear therapeutic target, and there are specific drugs for the target, before molecular targeted drug therapy can be performed. Most molecularly targeted therapies are currently used primarily for advanced cancer patients. For some patients with malignant tumors, even after radical surgery, although the mass disappears, molecular targeted therapy may be needed as an adjuvant therapy to eliminate the remaining tumor cells. Of course, molecular targeted drug therapy requires specific analysis of specific issues. Some patients may have obvious curative effect at the beginning of treatment, but over time, patients will develop drug resistance, and the curative effect will decrease accordingly.

  How to deal with resistance to molecular targeted therapy

  Any drug used for a long time will develop resistance, and the same is true of molecularly targeted drugs. If drug resistance occurs with molecularly targeted drugs, there are usually four options: re-do pathology, re-gene testing, direct replacement of targeted drugs, or re-accept chemotherapy. Among these methods, it is recommended to re-do genetic testing first. Taking molecular targeted therapy for lung adenocarcinoma as an example, many lung cancer patients can no longer withstand chemotherapy in the later stage, and many patients do not want to undergo chemotherapy, so they directly replace targeted drugs. This is a bit blind. Although it is now found that 50% to 60% of the first-generation chemotherapy drugs for lung cancer are resistant to the T790M mutation, and then the third-generation drugs are selected, this is only a probability, not everyone will have this situation. Therefore, it is recommended to re-run genetic testing and re-do pathology. Some people may not understand, in fact, one of the mechanisms of molecular targeted drug resistance is the change of pathological type. For example, the initial pathological diagnosis is lung adenocarcinoma, but after treatment, the pathological type may become small cell lung cancer. The changes in the human body are amazing and anything can happen. Therefore, in the process of using molecular targeted therapy, it is necessary to adhere to regular monitoring and observation of the condition. If the disease is found to progress, genetic testing is done again and the treatment plan is adjusted.

  Are there any adverse reactions

  to molecularly targeted drugs? Molecularly targeted drugs exert anticancer effects by acting on the oncogenic sites of cancer cells. These carcinogenic sites are often specific to tumor cells or more abundant in tumor cells, and normal cells do not contain or contain less, so in theory, targeted therapy only acts on or mainly acts on tumor cells, that is, a higher tumor It is specific and has less effect on normal tissue cells, which is also different from traditional chemotherapy. However, since some targets are not completely unique to cancer cells, and are also expressed to different degrees on normal cells, in fact, after targeted drugs enter the human body, they will also have a certain impact on normal cells, resulting in a variety of Adverse reactions. Most molecularly targeted drugs can cause adverse reactions, including fatigue, fever, rash, muscle and joint pain, etc., as well as common side effects of chemotherapy drugs such as gastrointestinal reactions, bone marrow suppression, and liver and kidney dysfunction. Therefore, when using molecularly targeted drugs clinically, the related adverse reactions should be closely observed, detected in time, and dealt with in time.

  In conclusion, molecular targeted therapy has brought great confidence and hope to tumor patients, and many patients with advanced tumors have achieved long-term survival through molecular targeted therapy. However, molecular targeted therapy is only one of many tumor treatment methods, and it is not a panacea. Cancer requires comprehensive treatment and precise treatment. Molecular targeted therapy needs to be selected correctly, and don't blindly believe in magic.



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