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Genetic mutation sites for predicting drug responsiveness to anti-her2 therapy in breast cancer patients and its application

A drug response and site technology, applied in the medical field, can solve problems such as restricting the development of individualized treatment of tumors, and achieve the effect of preventing drug waste.

Active Publication Date: 2021-10-01
CANCER INST & HOSPITAL CHINESE ACADEMY OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Therefore, tumor monitoring methods have seriously restricted the development of individualized tumor treatment, and have become a bottleneck to be solved urgently.

Method used

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  • Genetic mutation sites for predicting drug responsiveness to anti-her2 therapy in breast cancer patients and its application
  • Genetic mutation sites for predicting drug responsiveness to anti-her2 therapy in breast cancer patients and its application
  • Genetic mutation sites for predicting drug responsiveness to anti-her2 therapy in breast cancer patients and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1 Screening for gene mutation sites associated with drug resistance in breast cancer patients

[0053] 1. Patient and sample collection

[0054] A total of 120 female ABC patients who were being treated in a tumor hospital were collected. These patients were diagnosed as breast cancer by pathological examination; among them, 119 patients had non-invasive ductal carcinoma, and 1 patient had bone marrow carcinoma.

[0055] The level of HER2 positivity was defined by immunohistochemistry 3+, or immunohistochemistry 2+ / fluorescence in situ hybridization+ (FISH+). The breast cancer patients in this study were patients over 18 years old who were diagnosed with metastatic breast cancer. The patient's peripheral blood was collected using streck tubes and centrifuged within 72 hours to separate plasma from peripheral blood cells. This study was approved by the ethics committees of the Chinese Academy of Medical Sciences and the National Cancer Center / Tumor Hospital of ...

Embodiment 2

[0074] Example 2 HER2 point mutation c.3020C>T anti-HER2 therapeutic cell test

[0075] 1. Experimental materials

[0076] 1. Strains

[0077] Escherichia coli DH5α, stbl3, is preserved by the State Key Laboratory of Molecular Oncology, Chinese Academy of Medical Sciences (hereinafter referred to as "Key Laboratory").

[0078] 2. Plasmid

[0079] LentiCRISPRV2: Lentiviral expression vector, donated by the laboratory of Dr. Zhang Feng of the Massachusetts Institute of Technology, and its gel recovery product is preserved by the key laboratory.

[0080] LenticrisprV2-HER2: A lentiviral expression vector inserted into the corresponding sgRNA, constructed by this application. (See the experimental method section below for the specific construction method)

[0081] PCMV-GFP: green fluorescent protein lentiviral expression vector, preserved by key laboratories.

[0082] 3. Cell lines

[0083] BT474: Breast cancer cell line, preserved by key laboratories.

[0084] Cell line me...

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Abstract

The invention discloses a gene mutation site for predicting the responsiveness of breast cancer patients to anti-HER2 therapeutic drugs and the application thereof. Specifically, after large-scale screening by the inventors, it was found for the first time that the genotype at position 3020 of the HER2 gene coding sequence is associated with drug responsiveness to trastuzumab, lapatinib or pyrotinib in breast cancer patients. Based on the above research results, the present invention has developed a product that can be used to predict the drug responsiveness of breast cancer patients to trastuzumab, lapatinib or pyrotinib. The above products function by detecting the genotype at the 3020th position of the HER2 gene coding sequence, and can be widely used clinically.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to gene mutation sites for predicting the responsiveness of breast cancer patients to anti-HER2 therapeutic drugs, in particular to HER2 for predicting the drug responsiveness of breast cancer patients to trastuzumab, lapatinib or pyrotinib Gene mutation sites and their applications. Background technique [0002] Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-30% of breast cancer patients, and HER2 overexpression is associated with poor prognosis and high-grade malignancy. HER2 protein overexpression or HER2 gene amplification is also an important predictive biomarker for identifying breast cancer patients who would benefit from HER2-targeted therapy. Several preclinical and clinical studies have shown that the mechanism of HER2 activation involves not only HER2 protein overexpression and gene amplification, but also somatic mutations capable of activating HER2. The e...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6886C12N15/12
CPCC07K14/71C12Q1/6886C12Q2600/106C12Q2600/156
Inventor 马飞徐兵河易宗毕管秀雯刘斌亮李春晓
Owner CANCER INST & HOSPITAL CHINESE ACADEMY OF MEDICAL SCI
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