Esophageal cancer is a relatively common malignant disease in human digestive system. At present, radical surgery, adjuvant chemotherapy and radiotherapy are the main living means for the treatment of this disease, but more than half of the patients have no chance of radical surgery because they cannot all be detected early. Esophageal cancer is a common malignant disease in human digestive system. At present, radical surgery, adjuvant chemotherapy and radiotherapy are the main means to treat this disease clinically, but more than half of the patients have no chance of radical surgery because they cannot all be detected early. At the same time, due to different lesions of esophageal cancer and the same surgical method, recurrence and metastasis are more common after surgery, and for such patients, the possibility of secondary surgery is even smaller, so most of the clinic adopts palliative surgery chemotherapy, radiotherapy, biological therapy, Chinese medicine and other internal parts of comprehensive treatment, which has achieved certain efficacy, but still faces great challenges. In recent years, research on the pathogenesis of esophageal cancer has become a hot spot, and people try to understand its biological behavior at the molecular level. With the deepening of research, targeted therapy for esophageal cancer has also made some progress. Targeted therapy has created a new clinical field of esophageal cancer. I. Molecular targeted therapy (a) Epidermal growth factor and its inhibitors Epidermal growth factor (epidermalgrowthfactorreceptor, EGFR) is a transmembrane rod protein, which is an enzyme kinase (TK) growth factor receptor, and this receptor has an important role in regulating cell growth, differentiation and survival. Overexpression or overactivation of the lucine kinase receptor is seen in many tumors, such as EGF or transforming growth factor alpha (TGF-α) binding to EGFR, which is able to activate the receptor through the auto-phosphorylation of the corresponding enzymatic kinase, thereby stimulating an intracellular signal transduction chain reaction to DN.-synthesis. EGFR is now known to play an extremely important role in the growth, repair and survival of tumor cells, and its overexpression is often associated with poor prognosis, rapid metastasis and short survival. It has been shown that patients with esophageal cancer usually show high EGFR expression and correlate with disease resistance to chemotherapy and radiotherapy, and that blocking EGFR can arrest tumor cell growth. EGFR enzyme kinase activity can be selectively inhibited by drugs from within the cell membrane or competitively blocked by monoclonal antibodies from extracellular ligand binding sites. ZD1839 (Iressa, gefitinib) is a phenylephrine pot jelly compound, a potent inhibitor of the EGFR exhausted amino acid kinase, which acts as a blocker of the signaling pathway for proliferation, growth, and survival of cancer cells. It has been found to increase the tumor suppressive effect of drugs such as DDP, CBP, Taxol, Dacetaxel and ADM = The efficacy of gefitinib (an acetate kinase inhibitor) in combination with celecoxib in the treatment of patients with progressive esophageal cancer was reported in the 2004 American Society of Clinical Oncology Annual Meeting, which evaluated the effects of oral gefitinib and the CQX-2 inhibitor celecoxib (celecoxib) on patients who did not The study evaluated the efficacy and tolerability of oral gefitinib and the CQX-2 inhibitor celecoxib in patients with esophageal cancer who were not receiving chemotherapy. Three of the 15 patients in the phase H study had squamous cell carcinoma and 12 had adenocarcinoma. Except for one case of death due to esophageal cancer, the remaining 14 patients were evaluated for efficacy, with the first efficacy evaluation starting 2 months after treatment, resulting in 10 patients (71%) with progressive disease and 3 patients (21%) with stable disease. Tolerability was evaluated in all 15 patients, and the common adverse reaction was healing sore-like dermatitis, with grade 1 —–2 reactions in 6 (40%) patients. No treatment-related grade 3 —–4 adverse reactions were seen. The conclusions showed that gefitinib was generally well tolerated in combination with celecoxib. Due to the small size of the study, further studies are needed to determine this. However, the stabilization of three patients in this study suggests a possible role in the treatment of patients with esophageal cancer. EMD72000 is a fully humanized anti-EGFR antibody that has demonstrated antitumor activity and is well tolerated in phase I clinical trials in EGFR-positive solid tumors, and trials of EMD72000 in combination with EOX (epirubicin, oxaliplatin, capecitabine) for the treatment of low-grade esophageal and gastric cancers are ongoing. Gastrointestinal stromal tumors (GIST) have attracted a lot of attention from the oncology community in recent years and were originally described by Mazur and Clark in 1983. Prior to this, GIST was known as smooth muscle tumor, smooth muscle sarcoma, smooth muscleoblastoma, and epithelioid smooth muscle sarcoma. The esophagus near the base of the stomach is a good site for esophageal GIST. Immunohistochemical staining for CDi17 (C-kit) has a >95% positive rate. CDi17 antigen is an antigenic determinant cluster in the extracellular functional region of the cell surface enzyme kinase receptor (C-kit), whose ligand is stem cell factor (SCF).0 Activation of C-kit by SCF causes dimerization and phosphorylation of the receptor and initiates an intracellular signaling pathway that triggers a series of of cellular regulatory processes, including proliferation and differentiation. Although C-kit is expressed in several cell types, including GIST, ICC, mast cells, melanocytes, hematopoietic progenitors, and germ cells, it is rarely, if ever, expressed in such large numbers in other intestinal spindle cell tumors, such as smooth muscle tumors and malignant neuroectodermal tumors (Schwann cell tumors), and can therefore be used for differential diagnosis. Imatinib mesylate CImatinbmesylate, ST-571, Glivec, Glivec) is a derivative of α-monoglutethimide that selectively inhibits cooline kinases, including C-kit, BCR-ABL, and platelet-derived growth factor (PDGF) receptors. Imatinib binds to the ATP-binding site in the functional region of the intracellular enzyme kinase of C-kit, blocking the transfer of phosphogene from ATP to the protein substrate cooline residues, thereby inhibiting cell metaphase proliferation and causing apoptosis. (ii) Angiogenesis inhibitors Angiogenesis is essential for the growth and metastasis of most solid tumors, and recent studies have found that VEGF-C, a vascular endothelial growth factor (Vascularendothelialgrowthfactor (VEGF), is relatively specific for lymphatic vessel formation, and its receptor with VEGF, VEGFR-3 (also known as £ 1t-4) constitute a VEGF-C/VEGFR-3 paracrine pathway closely associated with tumor lymphangiogenesis. The expression of VEGF-C was also detected by immunohistochemistry in the tissues of 59 surgical specimens of esophageal squamous carcinoma, and the results were positive in 42 cases and significantly correlated with pathological graded metastasis, but highly correlated with lymphatic metastasis, with VEGF acting as a ligand binding to VEGFR-3 and acting as a lymphangiogenic factor, stimulating the mitosis of vascular endothelial cells by activating VEGFR-3, thus promoting vascular growth toward the tumor. Inhibition of angiogenesis is an important targeted therapeutic approach to control tumor growth, including inhibition of vascular growth stimulating factors (e.g., vascular endothelial growth factor) or their receptors and blockade of endothelial cell proliferation. Drugs that have been developed include Bevacizumab (Avastin) and the endothelial inhibitor endostatin. bevaci?zumab (Avastin, rhuMab-VEGF) is a recombinant human anti-VEGF ligand monoclonal antibody. endosta?tin is an endogenous anti-angiogenic factor, isolated from vascular endothelioma, that specifically inhibit vascular endothelial cell proliferation, angiogenesis and tumor growth. (C) cyclooxygenase-2CCOX-2) inhibitors Recent epidemiological studies have found that long-term use of non-steroidal anti-inflammatory drugs (non-steroidalanti-inflammatorydrugs, NSAID) such as aspirin can reduce the incidence of esophageal cancer by 50%r-.J90%. And NSAID is an inhibitor of cyclooxygenase (COX). Zhang et al. performed COX-2 gene protein expression assay on 51 cases of surgically resected specimens of esophageal cancer (21 cases of highly differentiated squamous carcinoma, 17 cases of moderately differentiated squamous carcinoma, and 13 cases of poorly differentiated squamous carcinoma), and the results showed that normal epithelial cells expressed less, while paraneoplastic tissue and highly differentiated squamous carcinoma expressed the highest, suggesting that COX-2 is involved in the formation of esophageal cancer. There are two mechanisms by which COX-2 causes tumors. One believes that COX-2 is involved in tumorigenesis and development through inhibition of apoptosis; the other believes that COX-2 causes neointimal hyperplasia, which is beneficial to tumor growth. The cREN of COX-2 was transfected with rat intestinal epithelial cells, and the apoptotic capacity of RIE-S cells was significantly enhanced, and the anti-apoptotic activity of RIE-S was inhibited with the COX-2 specific inhibitor SC58125. In endothelial and tumor cell cultures, cells highly expressed COX-2 and produced PG, proangiogenic factor, and stimulated both endothelial migration and test tube cell growth, a result that could be inhibited by the selective COX-2 inhibitor NS398, while controls did not highly express COX-2. It was also found that COX-2 regulates VEGF and tumor-associated angiogenesis through EP receptors. High expression of COX-2 was associated with p53. protein accumulation, and overexpression of COX-2 induced expression of NF-KB and angiogenic factors associated with anti-apoptosis, thereby promoting tumorigenesis. Souza et al. treated a human cancer cell line with the COX-2 specific inhibitor NS398 and found that it significantly inhibited tumor growth and increased apoptosis. The combination of COX-2 inhibitors and other related factors has been applied in the clinic, and its role remains targeted therapy.