Application of nop14 gene and its protein as a marker of tumor sensitivity to mTOR inhibitors

Abstract

The invention discloses the application of the NOP14 gene and its protein as a marker for tumor sensitivity to mTOR inhibitors. The first study of the present invention shows that the expression level of gene NOP14 in tumor cells is positively correlated with the sensitivity of tumor cells to mTOR inhibitors (rapamycin and its derivatives, such as everolimus), and those with high expression of gene NOP14 Tumors are sensitive to mTOR inhibitors, which can be used as an index for detecting and evaluating the sensitivity of tumor patients to mTOR inhibitors. Therefore, the present invention provides a new index for the clinical sensitivity detection of mTOR inhibitor drugs, using this gene as an index to design new chemical entities at the gene level and protein level, which can be quickly, conveniently and effectively Sensitivity detection of mTOR inhibitor drugs can improve the curative effect of mTOR inhibitor drugs on tumor patients, promote individualized treatment of tumors, and benefit patients better. It has 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 ...

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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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