December 4, 2022

Medical Trend

Medical News and Medical Resources

​HER2 Exon 20 YVMA Insertion Mutant Organoid Model

​HER2 Exon 20 YVMA Insertion Mutant Organoid Model

 

 

​HER2 Exon 20 YVMA Insertion Mutant Organoid Model.  The research of HER2 targeted drugs is full of opportunities and challenges, and the further development of new therapeutic drugs is imminent.

Human epidermal growth factor receptor 2 (Her-2) belongs to the ERBB receptor tyrosine kinase family. The family includes four members ERBB1, ERBB2, ERBB3 and ERBB4. Among them, ERBB2 is also called HER2. When it is combined with other ERBB family members, it forms a heterodimer. After the ligand binds to HER2, HER2’s own tyrosine kinase is activated, which in turn phosphorylates its substrate and activates downstream signal path.

 

Introduction to HER2 gene mutation and Current status of targeted drug therapy

HER2 gene mutation is a carcinogenic driver of lung cancer, which is mainly seen in women, non-smokers and patients with lung adenocarcinoma. It can also be found in other tumors, including breast cancer, ovarian cancer, bladder cancer, salivary gland tumors, endometrial cancer, pancreatic cancer, etc. Among them, the insertion mutation in exon 20 of the HER2 gene is the most common mutation type in HER2 mutant non-small cell lung cancer. It is more common in p.A775_G776insYVMA, and also includes p.G776>VC, p.P780_Y781insGSP, p.V777_G778insCG, p.M774delinsWLV , P.G776>LC and point mutations p.L755S, p.G776C and p.V777L.

 

​HER2 Exon 20 YVMA Insertion Mutant Organoid Model

 

At present, there is no standard treatment plan for HER2 gene mutant non-small cell carcinoma. According to reports, the drug treatments targeting HER2 mutations are shown in Table 1:

Table 1 Therapeutic effects of drugs targeting HER2 mutations

name

Test target

ORR

Median progression-free survival

TDM-1

HER2 mutant NSCLC

44%

5 months

Pozitinib

HER2 20 exon insertion mutation NSCLC

50%

5.1 months

Afatinib

G778_P780dup and G776delinsVC mutant subtypes

40%

7.6 months

Dacomitinib

HER2 exon 20 mutation

12%

no

TAK-788

EGFR exon 20 insertion mutation

43%

7.3 months

DS-8201

HER2 mutant breast and stomach cancer

61.9%

14 months

Previous studies have found that the median overall survival of patients with HER2 mutant advanced NSCLC is less than 2 years. Since the existing targeted drugs are not developed for mutant HER2, the clinical results of the treatment effect for a wide range of HER2 mutant lung cancers are quite different. . Therefore, in non-small cell lung cancer, the research of HER2 targeted drugs is full of opportunities and challenges, and the further development of new therapeutic drugs is imminent.

 

HER2 Exon 20 YVMA , Insertion mutant organoid model

On December 31, 2018, Professor Zhou Caicun and Ren Shengxiang from Shanghai Pulmonary Hospital Affiliated to Tongji University and Professor Ji Hongbin from Shanghai Institute of Biochemical Cell Research, Chinese Academy of Sciences collaborated in an article published online on “AnnalsofOncology”. The researchers successfully used the established The HER2-20 exon A775_G776YVMA insertion mutant lung adenocarcinoma organoids (organoids) model and human tumor xenograft (PDX) models have verified the anti-tumor activity of pyrrotinib, and are also in follow-up clinical trials (showing that pyrrotinib’s ORR 53.3%, median PFS was 6.4 months, median DOR was 7.2 months) further proved the correctness of the test, indicating that tumor organoids in vitro drug sensitivity test has a strong correlation with the results of clinical trials.

​HER2 Exon 20 YVMA Insertion Mutant Organoid Model.

 

Recently, Ketu Medical established a HER220 exon YVMA insert organoid model using samples of malignant pleural and ascites fluid. The mutation abundance reached 45.05%. It successfully maintained the gene mutation characteristics in the original tumor cells, which can be used for the majority of pharmaceutical companies and scientific research. The institute provides integrated CRO services such as HER2 targeted drug screening, new drug development and targeted therapy. Part of its product information is as follows:

HER220 Exon YVMA Brightfield photos of introgression organoids:

 

name  Test target  ORR  Median progression-free survival  TDM-1  HER2 mutant NSCLC  44%  5 months  Pozitinib  HER2 20 exon insertion mutation NSCLC  50%  5.1 months  Afatinib  G778_P780dup and G776delinsVC mutant subtypes  40%  7.6 months  Dacomitinib  HER2 exon 20 mutation  12%  no  TAK-788  EGFR exon 20 insertion mutation  43%  7.3 months  DS-8201  HER2 mutant breast and stomach cancer  61.9%  14 months

 

HE staining results:

 

Tumor cells isolated from malignant pleural effusion

Organoids (P3 generation)

Sanger sequencing:

 

Drug testing experiment:

 

 

(source:internet, reference only)


Disclaimer of medicaltrend.org