NOP14 gene and application of protein thereof as sensibility marker of tumor to mTOR inhibitor

Abstract

The invention discloses an NOP14 gene and application of protein thereof as a sensibility marker of tumor to an mTOR inhibitor. The first study shows that the expression level of the NOP14 gene in a tumor cell is positively correlated with the sensibility of the tumor cell to the mTOR inhibitor (rapamycin and a derivative thereof, such as everolimus), and the tumor highly expressed by the NOP14 gene is sensitive to the mTOR inhibitor, and can be used as a detection evaluation index of the sensibility of a tumor patient to an mTOR inhibitor drug. Therefore, a new index is provided for detectingthe sensibility to the mTOR inhibitor drug clinically, the NOP14 gene is taken as the index, a new chemical entity is designed in gene level and protein level, and the sensibility to the mTOR inhibitor drug can be rapidly, conveniently and effectively detected, so that the treatment effect of the tumor patient on the mTOR inhibitor drug is improved, the individual treatment on the tumor is promoted, the patient is more benefited, and the NOP14 gene has a good application value and prospect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. More specifically, it relates to the application of the NOP14 gene and its protein as a marker for the sensitivity of tumor patients to mTOR inhibitors (rapamycin and its derivatives, such as everolimus). Background technique [0002] The full name of mTOR is mammalian target of rapamycin (mammalian target of rapamycin), which is an evolutionarily conserved serine / threonine protein kinase. mTOR is a downstream effector molecule of many commonly mutated oncogenic pathways, such as PI3K / AKT. Therefore, mTOR is often overactivated in tumors, leading to a series of malignant changes such as rapid cell proliferation, anti-apoptosis, and metabolic abnormalities. It is an important target for tumor therapy. [0003] At present, more mTOR inhibitors are rapamycin (rapamycin). Rapamycin is a macrolide immunosuppressant isolated from a bacterium, which can effectively inhibit the growth of fungi, so ...

AI Technical Summary

Problems solved by technology

[0004] Although rapamycin and modified molecules have been used in the clinical treatment of advanced renal cancer, advanced breast cancer (ER+ / HER2-), giant cell astrocytoma, and pancreatic neuroendocrine tumors, due to, firstly, rapamycin Rapamycin and its derivatives only inhibit mTORC1, but not mTORC2. Second, rapamycin closes the S6K-dependent negative feedback to the IRS1-PI3K-PDK1 pathway, leading to feedback activation of Akt and eventual drug resistance. Therefore, rapamycin The scope of application of mycin and its derivatives is still narrow

[0005] Moreover, the antitumor efficacy of mTOR inhibitors will vary from person to person

For example, it is relatively clear that only patients with TSC1 and TSC2 gene mutations respond well to rapamycin drugs, because the inactivation of TSC1 / TSC2 will cause excessive activation of mTORC1

However, in tumors with overactivation of PI3K-Akt pathway, such as PTEN loss, HER2 gene amplification, constitutive activation of PI3K catalytic subunit, tumors with IGF-1R or EGFR overexpression, the activation of mTORC1 is also caused, but Rapa Mycins such as everolimus and temsirolimus are less effective

[0006] At present, the lack of effective sensitivity markers has been a key factor limiting the promotion of rapamycin drugs

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