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, and the commonly used monoclonal antibodies include Herceptin (Trastuzumab, Herceptin), Rituximab (Merova), IMC-C225 (cetuximab, Erbitux, Erbitux) and Bevacizumab (Avastin). , Avastin), etc.; small molecule compounds commonly used are: Glivec (STI51, Glivec), Iressa (ZD1839, Gefitinib, Eressa), Erlotinib (Tarceva, OSI-774, Troche), Sorafenib (Sorafenib, Doxorubicin), Sunitinib ( Sutent, SU11248, Sunitinib), Lapatinib (Lapatinib), Vandetanib (Vandetanib), Dasatinib (Sprycel, Dasatinib), etc. Herceptin (Trastuzumab) Herceptin (Trastuzumab) 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. It was approved by FDA in 1998 and is used in combination with tamsulosin 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 to respond to treatment with tamsulosin, anthracyclines and hormonal therapy. The main toxicities of Herceptin are infusion reactions and some cardiotoxicity; therefore, concomitant use with anthracyclines is not recommended. 1,2 Rituximab (melphalan) Rituximab (melphalan), a human/mouse chimeric monoclonal antibody targeting CD20, has been the most important advance 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 of 95%, including a CR of 55%, and PCR showed that this combination regimen cleared bcl-2-positive cells. positive cells. 1, 3 IMC-C225 (cetuximab, Erbitux, Erbitux) IMC-C225 (cetuximab, Erbitux) is the most clinically advanced anti-EGFR human/mouse chimeric monoclonal antibody available, and IMC-C225 in combination with CPT-11 in patients with EGFR-positive colorectal cancer who failed CPT-11 therapy 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, CF The side effects of IMC-C225 were mainly skin rash. The current study concluded that in colorectal cancer, the efficacy of K-ras gene is relatively good for wild type, while the efficacy of K-ras gene is poor for mutated type, and it is not recommended. Baselga J et al. used IMC-C225 in combination with cisplatin/carboplatin to treat 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%, 39.6% of patients with stable disease (SD) or mildly effective (MR). 1, 4 Bevacizumab (Avastin) Bevacizumab (Avastin) is a novel humanized monoclonal antibody against the vascular endothelial growth factor receptor that 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, colorectal and breast cancers, and in phase II clinical trials for the treatment of other solid tumors. Phase II clinical trial studies are also underway for the treatment of other solid tumors. In the treatment of non-small cell lung cancer, it is primarily used in combination with first-line chemotherapy regimens for patients with non-squamous cancer, no bleeding tendency, and no brain metastases. A clinical trial using Bevacizumab in combination with irinotecan as first-line treatment for advanced colorectal cancer has achieved positive results; a clinical trial using Bevacizumab monotherapy for advanced breast cancer showed an efficiency of 9.3% and a stability rate of 16% at a dose of 10 mg/Kg, which was easily tolerated by patients, and a study conducted by Kabbinavar F et al. A randomized controlled study of Bevacizumab combined with 5-FU/LV and 5-FU/LV alone in the treatment of advanced colorectal cancer showed that the efficacy of 5mg/Kg Bevacizumab combined with 5-FU/LV was significantly better than that of 5-FU/LV alone and was easily tolerated by patients, and Bevacizumab combined with chemotherapy is expected to become the first-line treatment option for colorectal cancer. 2. Small molecule compounds class of molecular targeted therapeutics 2. 1 Glivec (STI571, imatinib, Glivec) Glivec (STI571, imatinib, Glivec) is an inhibitor of tyrosine kinase No. 571 signal transduction and is a small molecule compound. In clinical phase I studies, 54 patients with chronic phase CML who failed previous interferon therapy achieved hematologic remission in the 300 mg to 1000 mg/day dose group with an efficiency rate of 100% and 98% achieved CR, 53% of which were cytogenetic remissions. Subsequent phase II clinical studies also showed a 59% efficacy rate in the cytocritical phase of CML with mild toxicities. The remission rate for Ph-positive acute lymphoblastic leukemia (ALL) was also as high as 70%, with 55% CR. In view of the drug’s high efficiency and low toxicity, the U.S. FDA took only nine weeks to approve the drug after receiving the filing. Glivec has also shown disease control rates of 80% to 90% for CD117(+) in gastrointestinal malignant stromal cell tumors (GIST). In addition to its tyrosine kinase receptor inhibition, Glivec may also be effective in leukemias caused by (5;12) chromosomal ectopic fusions with Tel-PDGFR. It may be effective in malignant gliomas (the most common brain tumor) that are highly antagonistic to chemotherapy and radiotherapy. 2,2 Iressa (ZD1839, Gefitinib, Eressa) Iressa (ZD1839, Gefitinib) is an oral epidermal growth factor receptor-tyrosine kinase (EGFR-TK) antagonist that is a small molecule compound. Iressa is currently used primarily for the treatment of non-small cell lung cancer (NSCLC) and has proven effective in breast, prostate, and head and neck cancers. The results of a phase II clinical trial using single agent Iressa in 142 advanced NSCLC patients who had failed chemotherapy with platinum-containing or Tasuti regimens showed an efficacy rate of (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 in Asians, adenocarcinoma, women and non-smokers. There was an efficacy advantage for Asian, adenocarcinoma, female and non-smokers. The use of ZD1839 in combination with chemotherapy is not beneficial and, therefore, chemotherapy in combination with ZD1839 is not recommended; the main toxicities of Iressa are gastrointestinal reactions and acne-like rash, which are easily tolerated by patients. 2,3 Erlotinib (Tarceva, OSI-774, Troche) OSI-774 (Tarceva, erlotinib, Troche) 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 second-line 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. The results of 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 combination chemotherapy drug clinical trial studies are also underway, with the main combination drugs being Tysodi, 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. 2,4 Sorafenib (Sorafenib, Doxorubicin) Sorafenib (Sorafenib) is a novel multi-targeted antitumor drug. It has dual anti-tumor effects, on the one hand directly inhibiting tumor growth by inhibiting the RAF/MEK/ERK signaling pathway; on the other hand indirectly inhibiting tumor cell growth by blocking the formation of tumor neovascularization through inhibiting VEGF and platelet-derived growth factor (PDGF) receptors. The most common adverse effects of sorafenib include hand-foot syndrome, fatigue, diarrhea, rash, hypertension, hair loss, pruritus and nausea, and loss of appetite. In a large phase III clinical trial, 905 patients with advanced renal clear cell carcinoma with a low to moderate Motzer score who had failed a single systemic anticancer therapy within the past 8 months were randomized, 451 to sorafenib and 452 to the placebo group. At the time of interim analysis, 222 patients had died, and the objective efficacy rates were 10% and 2% in the two groups, respectively, with one complete remission (CR) in the sorafenib group. In addition, 74% and 53% of patients in the two groups had stable tumors, with clinical benefit rates of 84% and 55%, respectively. Progression-free survival doubled in the sorafenib group compared with the placebo group, at 5, 8 and 2, 8 months, respectively (P=0,00001), and patients had a significantly better quality of life. At interim analysis, overall survival in the placebo group was 14,7 months, which had not been achieved in the sorafenib group. Since progression-free survival was significantly better in the sorafenib group than in the placebo group, patients who progressed in the placebo group were allowed to cross over to the sorafenib group after the interim analysis. Further analysis showed that patients in different subgroups benefited from treatment with sorafenib, including age greater than or less than 65 years, moderate or low Motzer score, previous use or no use of IL-2, presence or absence of liver metastases, and disease-free survival greater than or less than 1,5 years. It was based on the results of this Phase III randomized clinical trial that the FDA fast-tracked the approval of sorafenib as a treatment for advanced renal cell carcinoma on December 20, 2005. This was the first drug approved by the FDA for the treatment of kidney cancer in 10 years. In addition, preliminary results from clinical studies suggest that sorafenib has potential antitumor effects in solid tumors such as hepatocellular carcinoma, melanoma, and non-small cell lung cancer (NSCLC). 2,5 Sunitinib (Sutent, SU11248, sunitinib) Sunitinib is an orally administered small molecule drug that inhibits the tyrosine kinase activities of VEGF-R2, -R3, and -R1, as well as platelet-derived growth factor (PDGFR-β), KIT, FLT-3, and RET, achieving antitumor effects by specifically blocking these signaling A 4/2 regimen of 50 mg/d (4 weeks of dosing and 2 weeks of rest) is a dose intensive regimen that can be tolerated. Common adverse reactions are systemic reactions (e.g., malaise, weakness), gastrointestinal reactions (e.g., nausea, dyspepsia, diarrhea, or oral mucositis), hematologic reactions (neutropenia, thrombocytopenia), and cutaneous reactions (e.g., dermatitis, skin discoloration, or hair discoloration). sunitinib’s antitumor activity has been demonstrated in patients with a variety of advanced malignancies, including renal cell carcinoma, gastrointestinal mesenchymal tumors (GIST), neuroendocrine tumors, sarcomas, thyroid cancer, melanoma, breast cancer, colorectal cancer, and non-small cell lung cancer. The U.S. FDA recently approved sunitinib for marketing to treat GIST and advanced kidney cancer. The results of sunitinib are encouraging since there are currently no drugs available clinically for advanced GIST other than imatinib and few drugs for kidney cancer. 2005 ASCO meeting presented the results of two ongoing independent clinical studies of sunitinib for metastatic renal cell carcinoma. The first study enrolled 63 patients with metastatic renal cell carcinoma who had failed prior biologic therapy and were given sunitinib orally at 50 mg/d for 4 weeks with a 2-week discontinuation, and the observed partial remission rate by RECIST criteria was 40% (25/63 patients), with an additional 21 (33%) stable and 17 (27%) progressive. The median time to disease progression (TTP) was 8 and 7 months, and the median survival time was 16 months. In patients who achieved partial remission, the median time to remission was 12,5 months. The median time to achieve partial remission was 2, 3 months. The second study had similar enrollment criteria and included 106 patients. 41 (39%) of those evaluable for efficacy were effective, of whom 1 was in complete remission, 25 (23%) were stable, and 33 (31%) were progressive. Median TTP and median survival time were not achieved. 2,6 ZD6474 (Zactima, Vandetanib, Vandetanib) ZD6474 (Zactima, Vandetanib, Vandetanib) is a synthetic anilinoquinazoline compound that is an orally administered small molecule multi-targeted tyrosine kinase inhibitor (TKI) that acts on tumor cells simultaneously with EGFR, VEGFR and RET tyrosine kinases. It also selectively inhibits other tyrosine kinases, as well as serine/threonine kinases. Phase I clinical studies have shown dose-limiting toxicities of diarrhea, hypertension, and rash. Common toxicities are diarrhea, rash, nausea, vomiting, and asymptomatic QT interval prolongation. The toxicities are dose dependent in