Application of splenic tyrosine kinase as therapeutic target for intrahepatic cholangiocarcinoma

Abstract

The invention discloses an application of splenic tyrosine kinase as a therapeutic target for intrahepatic cholangiocarcinoma. Experiments find out that the expression of SYK in intrahepatic cholangiocarcinoma is increased. In-vitro cell and in-vivo animal experiments find out that the proliferation of intrahepatic cholangiocarcinoma can be effectively inhibited with the use of the SYK antagonistGS-9973, and the inhibiting effect is close to that of a first-line chemotherapeutic drug gemcitabine.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to the application of spleen tyrosine kinase as a therapeutic target for intrahepatic cholangiocarcinoma. Background technique [0002] Spleen tyrosine kinase (Spleen tyrosine kinase, SYK) gene was first cloned from pig spleen cDNA in 1991, encoding a non-receptor protein tyrosine kinase. The human SYK gene is located in the q22 region of chromosome 9. The SYK protein contains 635 amino acids. It is a kind of specific protein kinase that can catalyze the phosphorylation of tyrosine residues in substrate proteins, including receptor tyrosine kinases, cytoplasmic Type tyrosine kinases and nuclear tyrosine kinases. Tyrosine protein kinases can regulate signal transduction within and between cells, play an important role in cell differentiation, proliferation and spread, and are closely related to the occurrence and development of tumors. It plays an important role in autoimmune...

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Problems solved by technology

However, simple surgery cannot effectively treat most patients (the pathogenesis is unknown, lack of early diagnostic markers, and the chance of surgery has been lost when it is discovered), and the postoperative survival rate is low (5-year survival rate is 8% to 47%). High rate (postoperative intrahepatic recurrence rate of 46% to 68%); non-surgical patients lack effective treatment means, local treatment may benefit a single lesion <3cm, and residual or local recurrence after surgery (overall curative effect Worrying); for unresectable or metastatic advanced cholangiocarcinoma, the chemotherapy regimen of gemcitabine combined with platinum antineoplastic drugs can prolong the survival of patients with cholangiocarcinoma, but it is limited by drug toxicity and drug resistance; radiotherapy alone The curative effect is very limited, and it is often used as an adjuvant therapy. There is no evidence that intraoperative radiotherapy and intraductal brachytherapy are better than standard chemotherapy, combined chemotherapy and radiotherapy for advanced cholangiocarcinoma

So far, there is no standard targeted drug for cholangiocarcinoma, and it is only in the stage of exploration and clinical trials, and there is no conclusion of definite curative effect

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