Application of NDUFA4L2 in drug resistance of herceptin

Abstract

The invention belongs to the field of gene engineering, and particularly relates to an application of NDUFA4L2 in preparation of medicines for reversing breast cancer herceptin resistance. By constructing a breast cancer stable cell strain resistant to herceptin, NDUFA4L2 can play a role in reversing the drug resistance of HER-2 positive breast cancer cells to herceptin at the cellular level. According to the invention, firstly, whole genome analysis is carried out on herceptin sensitive or drug-resistant cells, 487 probes are adopted in total, FDR correction is carried out, 453 differentially expressed genes are found, NDUFA4L2 is the gene with the most significant difference, and the sensitivity to herceptin is regulated and controlled through energy metabolism and oxidative stress level of NDUFA4L2. When being applied clinically, the herceptin gene can contribute to formulation of a treatment scheme of a clinician, prognosis judgment and become a target for research and development of related drugs in the future, the curative effect of herceptin is improved, and the herceptin has a good clinical popularization value.

Description

technical field [0001] The invention belongs to the field of genetic engineering, and particularly relates to the effect of overexpression of NDUFA4L2 participating in reversing the drug resistance of HER-2 positive breast cancer cells to Herceptin. Background technique [0002] Breast cancer is the most common malignant tumor in women, and its incidence rate is increasing year by year. It ranks first in the death of female tumors. Among them, HER-2 positive patients account for 20-30%, and the prognosis of these patients is poor. [0003] Herceptin is a humanized monoclonal antibody targeting the extracellular domain of the receptor tyrosine kinase encoded by HER-2, and is currently the most commonly used clinical drug for treating HER-2 positive breast cancer patients. [0004] Although Herceptin improved the survival of patients with HER-2-positive breast cancer, more than 70% of patients developed drug resistance within 1 year after treatment. Therefore, the drug resist...

AI Technical Summary

Problems solved by technology

[0006] ① Increased expression of HER-1, HER-2 or HER-3 on the surface of tumor cells leads to a decrease in the potency of antibody drugs;

[0009] In order to reverse the drug resistance of Herceptin, there are currently clinical drugs developed for the drug resistance mechanism, such as HER-2 tyrosine kinase inhibitor (TKI) lapatinib, blocking HER-2 / HER-3 Pertuzumab formed by heterodimers, etc. These drugs can be combined with Herceptin to improve the efficacy of Herceptin, but patients will eventually develop drug resistance and lead to disease progression

[0010] Existing studies can only partially clarify that the activation of EGFR family-related signaling pathways may only represent the tip of the iceberg of Herceptin resistance, but there are few studies on new methods for reversing drug resistance, so how to reverse or delay Herceptin resistance The drug can greatly prolong the survival time of HER-2 positive breast cancer patients and save the treatment cost of patients, which has important clinical significance and social benefits

[0011] At present, there is little research on the mechanism of Herceptin resistance, and there are few studies on the interaction between HER2-driven tumorigenesis and tumor cell energy metabolism

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