Lung cancer is one of the malignant tumors with the highest morbidity and mortality worldwide. Lung cancer can be divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) according to histological type, accounting for about 85% and 15% respectively. Among them, NSCLC is divided into squamous cell carcinoma, adenocarcinoma, large cell carcinoma and other rare types. At present, the traditional treatment methods for lung cancer are mainly surgery combined with radiotherapy and chemotherapy. Because most of the patients are diagnosed at an advanced stage, and the traditional treatment cycle is long and the side effects are large, the treatment effect on lung cancer patients is not ideal. Therefore, it is necessary to further explore the molecular mechanism of lung cancer in order to find effective drugs for the treatment of lung cancer as soon as possible. CD BioSciences provides precise In Vivo transfection services of lung cancer to assist in the study of the molecular functions of lung cancer-related genes.

Target Genes Delivered In Vivo in Lung Cancer

Through bioinformatics analysis, compared with normal tissues, genes such as EGFR, ALK, ROS1, NTRK, BRAF, RET, MET, HER2, and NRG1 were abnormally expressed in lung cancer.

Figure 1. Therapies targeting the key oncogenic signaling pathways in lung cancer.(Yuan M, et al.; 2019)

EGFR

Epidermal growth factor receptor (EGFR) is widely expressed on the surface of mammalian cell membrane and is the expression product of proto-oncogene c-erbB1. Mutations in EGFR can lead to abnormal and continuous activation of tyrosine kinases (TKs), resulting in uncontrolled cell growth and cancer.

ALK

Anaplastic lymphoma kinases are part of a family of proteins known as receptor tyrosine kinases (RTKs). This family of proteins transmits signals from the cell surface into the cell through a process called signal transduction. In NSCLC patients, ALK gene rearrangement accounts for 4%-7%.

ROS1

ROS1 fusions have been found in NSCLC patient samples and cell lines, with a positive rate of 1% to 2%. ROS1 belongs to a haplotype receptor tyrosine kinase (RTK) of the insulin receptor family. In NSCLC, the ROS1 gene is mainly fused with CD74 and SLC34A, and continuously activates the ROS1 tyrosine kinase region and downstream signal transduction pathways such as JAK/STAT, PI3K/AKT, and RAS/MAPK, thereby causing tumorigenesis.

NTRK

Tropomyosin-related kinase (Trk) is a kind of nerve growth factor receptor, its family members include highly homologous tropomyosin-related kinase A (TrkA), TrkB and TrkC, encoded by NTRK1, NTRK2 and NTRK3 genes, respectively. NTRK gene fusions occur in a variety of adult and pediatric solid tumors. In common cancers such as non-small cell lung cancer, the incidence of NTRK gene fusions is low (0-1%).

BRAF

BRAF gene, located on chromosome 7q34, encodes a serine/threonine protein kinase and is a member of the RAF family. BRAF gene alterations include BRAF mutation, BRAF kinase domain duplication, and BRAF fusion. According to the signal transduction mechanism and kinase activity, BRAF gene alterations can be further classified into: V600 mutant kinase-activating monomers (class I), kinase-activating dimers (class II), and kinase-inactive heterodimers (class III). kind). Among them, the V600 mutations with carcinogenesis and therapeutic value mainly include V600E and V600K mutations, which can cause downstream activation and cause cancer, accounting for half of the overall BRAF mutations.

RET

Rearrangement gene transfection (RET) is located on chromosome 10, encoding an RTK that exists on the cell membrane, and its mutation types mainly include fusion mutations with KIF5B, TRIM33, CCDC6, and NCOA4 genes, as well as point mutations at M918T alleles. The positive rate of RET in NSCLC is about 2%.

MET

Mesenchymal epidermal transforming factor (c-MET), the mesenchymal epithelial transforming factor, is a proto-oncogene located on the long arm of chromosome 7. c-MET protein is the tyrosine kinase receptor of hepatocyte growth factor (HGF). After the c-MET receptor binds to HGF, it is phosphorylated on the Y1234 and Y1235 tyrosine residues of the tyrosine kinase domain, This in turn leads to phosphorylation of C-terminal Y1349 and Y1356. After c-MET is activated, it can recruit and phosphorylate a variety of effector proteins at the C-terminus, such as phospholipase Cγ (PLCγ), SRC, growth factor receptor binding protein 2 (Grb2) and its related protein Grb1, and transcription activator STAT. Proteins and adapter proteins. Activated GAB1 becomes the binding site for downstream proteins (SHP2, PI3K, etc.), enters the nucleus through the RAS-MAPK and PI3K-AKT signal transduction pathways, affects gene expression and cell cycle, and promotes the growth, invasion, migration and angiogenesis of tumor cells.

HER2

HER2 is one of the important members of the ERBB family, and others include EGFR (HER1), HER3 and HER4. HER2 receptors are activated by forming homologous or heterodimers with other ERBB family receptors, leading to enhanced EGFR signal transduction and promoting the continuous differentiation, proliferation and metastasis of tumor cells. Oncogenic activation of HER2 can be caused by HER2 protein overexpression, gene amplification or gene mutation, and can occur in a variety of malignant tumors, including breast cancer, gastric cancer, and lung cancer.

NRG1

Neuregulin-1 (NRG1) fusion gene is a rare driver gene with druggability. NRG1 is a member of the EGF ligand family and can bind to HER/ErbB family RTKs. When the NRG1 gene is fused, it will bind to ERBB3 as a ligand to promote the homodimerization of ERBB3 or the formation of heterodimerization with ERBB2, thereby activating the downstream signaling pathway. The overall incidence of NRG1 fusion in solid tumors is 0.2%, and the positive rate of NSCLC is about 0.3%.

In addition to the above genes, there are interesting lung cancer-related genes that need to be explored and studied. Therefore, there is a need for an In Vivo transfection system that can precisely target lung cancer tissue and be taken up by tumor cells to function in vivo. The system can help researchers overcome various challenges encountered during In Vivo transfection:

• Relevant molecular function studies can only be carried out in vitro, lacking important In Vivo data
• Using in vitro transfection system for In Vivo transfection, the transfection efficiency is very low;
• The In Vivo transfection system used is not specific to Lung cancer tissues and cells, and is toxic to the body;
• The In Vivo transfection system used cannot penetrate the Lung cancer tissue into the tumor tissue;
• The nucleic acid load of the In Vivo transfection system is low, and it is difficult to achieve the expected effect;
• Etc…

Our Advantage:

• We can provide an In Vivo transfection system for Lung cancer tissues and cells to achieve efficient transfection
• Our system can target multiple targets at the same time, improving targeting accuracy
• The In Vivo transfection system has low toxicity to the body and is safe to use
• In Vivo transfection system vectors can protect nucleic acids from degradation during In Vivo delivery
• Persistent knockout effect in experimental animals after a single injection
• The system load is high, and the transfection needs of different doses can be completed
• Professional design and service team to provide you with reliable service and technical support
• Timely feedback of technical reports

CD BioSciences specializes in developing transfection systems and customizing transfection reagents for gene transfection using our core technologies. With our high-quality products and services, your transfection results can be greatly improved. If you can't find a perfect In Vivo transfection system, you can contact us. We can provide one-to-one personal customization service.

References

1. WOOD S L, et al.; Molecular histology of lung cancer: from targets to treatments. Cancer Treat Rev. 2015, 41(4): 361-375.
2. WU Y L, et al.; Dacomitinib versus gefitinib as first-line treatment for patients with EGFRmutation-positive non-small cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017, 18(11): 1454-1466.
3. SOLOMON B J, et al.; Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-mutation-positive non-small cell lung cancer. J Clin Oncol. 2018, 36(22): 2251-2258.
4. DRILON A, et al.; ROS1-dependent cancers-biology, diagnostics and therapeutics. Nat Rev Clin Oncol. 2020.
5. COCCO E, et al.; NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018, 15(12): 731-747.
6. CHAVDA J, BHATT H. Systemic review on B-RAF (V600E) mutation as potential therapeutic target for the treatment of cancer. Eur J Med Chem. 2020, 206: 112675.
7. LI A Y, et al.; RET fusions in solid tumors. Cancer Treat Rev. 2019, 81: 101911.
8. DRILON A, et al.; Targeting MET in lung cancer: will expectations finally be MET?. J Thorac Oncol. 2017, 12(1): 15-26.
9. Yuan M, et al.; The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Signal Transduct Target Ther. 2019, 4:61.

* For research use only. Not for use in clinical diagnosis or treatment of humans or animals.