Medical application of highly expressed TrkB as novel target to inhibition of pancreatic cancer metastasis
A high-expression, pancreatic cancer technology, applied to medical preparations containing active ingredients, pharmaceutical formulas, anti-tumor drugs, etc.
Inactive Publication Date: 2020-01-03
XI AN JIAOTONG UNIV
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[0002] The existence of tumor stem cells with stem cell characteristics capable of self-renewal has been found and identified in almost all known tumors, and the existence of tumor stem cells was first confirmed from the perspective of clinical practice at the end of 2010, but there are still different opinions on its source while in confusion
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[0035] The applicant's research analysis and experiments are described in detail below.
[0036] Tumor metastasis is a multi-step, inefficient process. The impact of fluid mechanics in blood vessels and lymphatic vessels, hypoxia, lack of nutrition, immune system attack and uncomfortable tissue microenvironment will all pose a fatal threat to metastatic tumor cells. Therefore, the applicant realized that the distant metastasis of tumor cells is not accomplished by a single cell alone, but only by aggregating to form a large aggregate (cell aggregate, usually >50 cells) to form a moving tumor microenvironment (moving microenvironment). Guaranteed transfer validity. Our previous studies found that TrkB of the nerve growth factor receptor family is necessary to maintain the formation of this large aggregate. For example, we found that TrkB can phosphorylate the cytoskeleton protein β-Catenin by activating its downstream protein kinase C (protein kinase C; PKC) signaling pathway...
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The invention proposes medical application of highly expressed TrkB as a novel target to inhibition of pancreatic cancer metastasis, for example, application of an inhibitor of TrkB (highly expressedTrkB) in the preparation of a drug for inhibiting metastasis of pancreatic cancer cells. It is cleared for the first time that the TrkB has the ability to promote cell fusion between the pancreatic cancer cells and bone marrow migration stem cells or pancreatic tissue stem cells to form tumor stem cells, a TrkB-mediated cytocannibalism phenomenon outside large aggregate participates in maintenanceof structural integrity of metastatic cancer cell large aggregate, and the pancreatic cancer metastasis large aggregate may achieve the purpose of immune escape by releasing microvesicles of the highly expressed TrkB to inhibit the cellular immunity of a body; and therefore, by inhibiting the formation of the tumor metastasis large aggregate or destroying the already formed large aggregate, therapeutic effects in inhibiting pancreatic cancer metastasis can be achieved.
Description
technical field [0001] This application relates to a marker and therapeutic target for pancreatic cancer metastasis. Background technique [0002] The existence of tumor stem cells with stem cell characteristics capable of self-renewal has been found and identified in almost all known tumors, and the existence of tumor stem cells was first confirmed from the perspective of clinical practice at the end of 2010, but there are still different opinions on its source And in confusion. [0003] Pancreatic cancer is an insidious, extremely dangerous and highly malignant digestive system tumor with rapid progression, early metastasis, low surgical resection rate, easy recurrence and metastasis after operation, and is insensitive to conventional chemotherapy and radiotherapy. Its morbidity and mortality are almost equal. There has been no breakthrough in its treatment for many years, the 5-year survival rate is still <5%, and the overall survival rate has not improved significan...
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IPC IPC(8): C12Q1/02A61K45/00A61P35/04
CPCA61K45/00A61P35/04G01N33/5011
Inventor 张勇魏炜张昊袁达伟朱琨李康王直郝楠贾瑞
Owner XI AN JIAOTONG UNIV