Tumor molecular targeted therapies are commonly used to target cell receptors, signaling and anti-angiogenesis. There are two main categories of such drugs, monoclonal antibodies and small molecule compounds. The commonly used monoclonal antibodies include: Trastuzumab (Herceptin), Rituximab (Mebthera), IMC-C225 (cetuximab, Erbitux) and Bevacizumab ( Avastin), etc.; small molecule compounds commonly used are Glivec (STI51, Imatinib), Iressa (ZD1839, Gefitinib) and OSI774 (Erlotinib , Tarceva ), etc. Chen Bebe, Department of Internal Medicine, Henan Cancer Hospital 1 Monoclonal antibodies 1.1 Trastuzumab, Herceptin Herceptin is a human/mouse chimeric monoclonal antibody targeting HER-2/neu proto-oncogene product, which can specifically act on HER-2 receptor overexpressed breast cancer cells. approved by US FDA in 1998, in combination with Tysol It can be used as a first-line treatment option for advanced breast cancer with HER-2/neu overexpression or unsuitable for treatment with anthracyclines. As a single agent, it can be used as a third-line treatment for advanced breast cancer that has failed treatment with tamsulosin, anthracyclines and hormone therapy. Significant efficacy has been achieved either in combination or as a single agent. One group of clinical trials showed that Herceptin monotherapy for advanced breast cancer with HER-2/neu++ or ++++ had an efficiency of 24%; the results of a phase II clinical trial of Herceptin monotherapy for advanced breast cancer with HER-2/neu++ or ++++ in China showed that the efficiency was 25.8%; compared with chemotherapy alone Herceptin combined with adriamycin, cyclophosphamide or paclitaxel for metastatic breast cancer significantly improved the efficacy. Clinical trials of Herceptin in combination with endocrine therapy for HER-2/neu++ or ++++ advanced breast cancer are also underway; a number of clinical trials have reported the use of Herceptin in combination with chemotherapeutic agents including The main toxic side effects of Herceptin are infusion reactions and some cardiotoxicity; therefore, it is not recommended to use it together with anthracyclines. 1.2 Rituximab, Mebthera is a human/mouse chimeric monoclonal antibody targeting CD20, which is the most important development in the treatment of low-grade malignant lymphoma in recent years. In low-grade malignant B-cell lymphoma that has relapsed despite repeated chemotherapy, one study reported that Rituximab monotherapy as first-line treatment for low-grade malignant B-cell lymphoma was maintained for 6 months in those who were effective and stable, with an evaluated efficacy rate of 47% at 6 weeks and an overall efficacy rate of 73% at 6 months, of which 37% were CR. Progression-free remission was up to 34 months and was extremely well tolerated by patients. The combination of Rituximab and CHOP regimen for the treatment of low-grade malignant B-cell lymphoma showed an overall efficacy rate of 95%, including a CR of 55%. PCR showed that this combination regimen cleared bcl-2-positive cells; another study showed that the combination of Rituximab and fludarabine had an efficacy rate of 93%, including a CR of 80%, and this regimen companion cleared bcl-2-positive cells. positive cells. Another study combining Rituximab and IL-2 for follicular non-Hodgkin’s lymphoma also achieved satisfactory results with an efficiency of 55% and was easily tolerated by patients. a multicenter clinical phase II trial led by R. Drapkin et al. who used Rituximab in combination with Pentostatin (pentostatin, an enzyme inhibitor) for the treatment of low-grade malignant B-cell lymphoma, and the results showed an efficiency rate (CR+PR) of 77%, with 22.3% CR and a remaining 19.3% patients in stable (SD) condition, and easily tolerated by patients. Another study using Rituximab in combination with chemotherapy for B-cell acute lymphoblastic leukemia is also underway. Other new monoclonal targeted therapies for hematologic malignancies include ibritumomab, trastuzumab, gemtuzumab, alemtuzumab, Hu1D10, epratuzumab, and alemtuzumab, all of which are being studied in clinical trials.1.3 Cetuximab Cetuximab, IMC-C225, Erbitux Erbitux is the most clinically advanced anti-EGFR human/mouse chimeric monoclonal antibody, and clinical phase II trial studies have shown that IMC-C225 alone or in combination with chemotherapy is an effective regimen for the treatment of patients with metastatic or recurrent head and neck tumors; Baselga J [14] et al. used IMC-C225 in combination with E. S. Kim et al. treated 96 patients with metastatic or recurrent head and neck squamous carcinoma that had failed to respond to platinum-based therapy with an effective rate (CR+PR) of 14.6% and stable (SD) or mildly effective (MR) disease in 39.6% of patients. e. S. Kim et al. treated 20 patients with advanced non-small cell lung cancer that had failed chemotherapy with IMC-C225 in combination with Tysol D. The effective rate (PR) was 20% (4 cases), 30% of patients (6 cases) had stable disease (SD); a phase II clinical trial study of IMC-C225 in combination with CPT-11 in EGFR-positive colorectal cancer patients who failed CPT-11 treatment showed that the single agent efficiency was 11% and the combination of CPT-11 was 22% efficient and easily tolerated by patients.IMC-C225 in combination with CPT-11+5- IMC-C225 in combination with CPT-11+5-FU+CF improves the efficacy of chemotherapy in EGFR-positive colorectal cancer; Rosenberg AH et al. used IMC-C225 in combination with CPT-11 and 5-FU and CF to treat patients with EGFR-expressing primary colorectal cancer treated with platinum, with an efficiency of 44%, and in cases where CPT-11 treatment failed, the efficiency was still 22.5%. C225 side effects were mainly skin rash. Since IMC-C225 is a human/mouse chimeric monoclonal antibody, although its murine origin has been greatly reduced by the humanization of the antibody stabilization zone, there is still the problem of heterologous variable zone, and multiple applications still affect the efficacy from the production of human anti-mouse antibodies. The clinical trial of its fully humanized monoclonal antibody EMD-72000 for EGFR-positive solid tumors showed an efficiency of 23% and a stabilization rate of 27%, which is easily tolerated by patients, and further studies are in progress. endothelial growth factor receptor humanized monoclonal antibody, is expected to be a first-line treatment option for colorectal cancer and is currently being studied in phase III clinical trials for the treatment of non-small cell lung cancer, colorectal cancer and breast cancer, and phase II clinical trial studies are ongoing for the treatment of other solid tumors. A clinical trial using Bevacizumab in combination with irinotecan as first-line treatment for advanced colorectal cancer has shown positive results; a clinical trial using Bevacizumab monotherapy for advanced breast cancer showed an efficiency rate of 9.3% and a stability rate of 16% at a dose of 10 mg/Kg, which was easily tolerated by patients; a study conducted by Yang JC et al. A randomized controlled study of Bevacizumab monotherapy in advanced kidney cancer conducted by Yang JC et al. showed that Bevacizumab significantly prolonged progression-free remission in patients with advanced kidney cancer; A randomized controlled study of Bevacizumab combined with 5-FU/LV and 5-FU/LV alone in advanced colorectal cancer conducted by Kabbinavar F et al. showed that 5 mg/Kg Bevacizumab Bevacizumab combined with chemotherapy is expected to be the first-line treatment option for colorectal cancer.2 New molecularly targeted therapeutic agents in the class of small molecule compounds2.1 Imatinib Imatinib,Glivec,STI-571 is an inhibitor of tyrosine kinase No.571 BCR-ABL-induced tyrosine kinase (TK) is an important link in the pathogenesis of chronic granulocytic leukemia (CML), and Glivec specifically binds to the BCR-ABL gene’s ATP site, inhibits the activity of this enzyme, blocks tumor cell signaling, and selectively inhibits tumor growth without affecting the function of normal cells. In the clinical phase I study, 54 patients with chronic phase CML who failed previous interferon therapy in the dose group of 300mg~1000mg/day achieved hematological remission with 100% efficiency and 98% achieved CR, 53% of which were cytogenetic remission. A subsequent phase II clinical study showed a 59% efficacy rate also in the cytocritical phase of CML with mild toxicities. The remission rate in Ph-positive acute lymphoblastic leukemia (ALL) was also as high as 70%, including 55% CR. Glivec also showed 80% to 90% disease control in patients with gastrointestinal malignant stromal cell tumors (GIST); Stroobants S evaluated 13 cases of Glivec for GIST using positron excitation computed tomography (PET). The efficacy of Glivec in the treatment of GIST was 100%, with 11 cases of CR and 2 cases of PR. Furthermore, in addition to its role in inhibiting tyrosine kinase receptors, Glivec supported malignant mosaicism? Glivec is also effective in leukemias caused by chromosomal ectopic fusion with Tel-PDGFR. Potentially effective in malignant gliomas (the most common brain tumor) that are highly antagonistic to chemotherapy and radiation, Glivec has been shown to inhibit the growth of malignant glioma cells injected into the brain of nude mice, suggesting that this drug may have a role in treating some currently incurable diseases. At the 38th ASCO meeting, a clinical trial using Glivec for small cell lung cancer was reported, suggesting that it is easily tolerated by patients, but specific efficacy has yet to be further investigated.2.2 Gefitinib Gefitinib, Eressa Iressa, ZD1839 is an oral epidermal growth factor receptor-tyrosine kinase (EGFR-TK) antagonist, a small molecule compound EGFR expression is related to the tyrosine kinase activity of tumor cells, and EGFR overexpressed tumor cells receive cellular growth signals that activate intracellular expression of certain genes, accelerating cell differentiation and releasing more cells. EGFR overexpression can accelerate cell differentiation and release more angiogenic factors and pro-metastatic factors. Inhibition of EGFR overexpression can inhibit the growth of tumor cells. Iressa is currently used to treat non-small cell lung cancer (NSCLC) and has been shown to be effective in breast cancer, prostate cancer and head and neck tumors. The results of a clinical phase II trial using single-agent Iressa in 142 advanced NSCLC patients who had failed chemotherapy with platinum-containing or Tysodi regimens showed that the efficiency rate was (CR+PR ) 14% (9/66) in the 250 mg/day dose group and (CR+PR ) 8% (6/76) in the 500 mg/day dose group, with better efficacy in women and nonsmokers , the use of ZD1839 in combination with chemotherapy has no benefit to chemotherapy, therefore, the combination of chemotherapy and ZD1839 is not advocated; other studies reported that monotherapy for advanced NSCLC that failed chemotherapy could achieve a disease control rate of 53% (CR+PR+SD); the use of ZD1839 for the treatment of NSCLC and other solid tumors also improved the quality of life of patients; ZD1839 is useful for radiotherapy in The results of a clinical phase II trial using Iressa in advanced squamous head and neck cancer reported an effective rate (CR+PR) of 10.6%, a disease control rate (CR+PR+SD) of 53%, and a median survival of 8.1 months. The main toxicities of Iressa are gastrointestinal reactions and acne-like rash, which are easily tolerated by patients. 2.3 OSI-774, Tarceva, erlotinib is also an epidermal growth factor receptor-tyrosine kinase (EGFR-TK) antagonist, a small molecule compound, which was approved by the US FDA in September 2002 as a secondary treatment for advanced NSCLC that has failed to respond to standard regimens. In September 2002, the FDA approved it as a second- or third-line treatment option for advanced NSCLC that has failed to respond to standard regimens. A phase II clinical trial study of OSI-774 monotherapy for relapsed advanced non-small cell lung cancer showed an efficiency of 12.3% and a stability rate of 38.6%; another phase II clinical trial study of OSI-774 monotherapy for fine bronchoalveolar carcinoma showed an efficiency of 26%; OSI-774 was also effective in head and neck tumors and ovarian cancer; a phase III clinical trial study of combination chemotherapy for pancreatic cancer is also underway. Phase III clinical trial studies are also underway; several clinical trial studies of combination chemotherapeutic agents are also underway, with the main combination agents being Tysol D, Kinzel + Cisplatin, and Carboplatin + Tysol. In Europe, a phase III clinical trial study of OSI-774 in combination with Kinzel + cisplatin for non-small cell lung cancer was conducted; in the United States, a phase III clinical trial study of OSI-774 in combination with Tysol + carboplatin for non-small cell lung cancer was also conducted; a phase III clinical trial study of combination chemotherapy for pancreatic cancer is also underway; some clinical trial studies have preliminary results: L. Forero et al. combined OSI-774, thaumatin and carboplatin to treat 9 patients with malignancy. Thaumatin and carboplatin were given 3 days before the first cycle of OSI-774 treatment, and 1 non-small cell lung patient approached CR, 1 non-small cell lung person and 1 penile cancer patient reached MR with stable disease for more than 4 months, and OSI-774 did not significantly increase the toxic side effects of chemotherapy. Studies of OSI-774 for colorectal cancer have also shown efficacy.2.4 Other small-molecule compound-targeted therapeuticsOther small-molecule compound-targeted drugs include CI-1033, an irreversible erb tyrosine kinase inhibitor; PKI166 and GW572016, both bifunctional tyrosine kinase inhibitors that inhibit both EGFR and Her-2 inhibitors; SCH66336, a protein kinase C inhibitor; LY317615, a protein kinase Cb inhibitor; TNP-470, a vascular endothelial inhibitor; SU6668, SU11248, PTK787/ZK222584 and ZD6474, all vascular endothelial growth factor receptor inhibitors; SCH66336 ( lonafarnib) and R115777, both farnesol protein transferase inhibitors that specifically inhibit multidrug resistance protein 1 and protein 2, of which R115777 has shown positive efficacy in phase I clinical trials in combination with the chemotherapeutic agent irinotecan for the treatment of advanced tumors.