Kidney cancer is one of the most common tumors of the urinary system. About 400,000 people around the world suffer from malignant kidney tumors every year, and 175,000 of them die from this disease. Among them, metastatic renal cell carcinoma (mRCC) is not sensitive to conventional radiotherapy and chemotherapy, has a poor prognosis and high mortality, which poses a great threat and impact on the lives of patients. For this reason, there is a need for more efficient therapeutic drugs to treat renal cancer clinically. However, the development of highly effective drugs is based on an in-depth understanding of the pathogenesis of renal cell carcinoma ( RCC). Therefore, research tools that more truly reflect the function of expression products of corresponding genes in the body are needed. CD BioSciences has developed an in vivo precise transfection system in order to achieve a more accurate reflection of gene function in vivo.

Target Genes Delivered In Vivo in Renal Cancer

According to the existing reports, the related genes that have been focused on as the targeted therapy sites of renal cancer include: VHL, PBRM1, SETD2, BAP1, KDM5C, PTEN/PI3K/AKT/mTOR pathway genes, TP53 and MET.

Figure 1. Biomarker Development for Metastatic Renal Cell Carcinoma. (Miron B, et al.; 2020)

VHL

VHL gene belongs to tumor suppressor gene, and its encoded product is E3 ligase, which constitutes VHL complex and targets HIF protein to degrade its ubiquitination. VHL is a highly mutated gene in clear cell renal cell carcinoma (ccRCC), and 52% of ccRCC in the TCGA database carry VHL mutations. The downstream HIFα-VEGF of VHL can be used as a target to treat VHL-associated ccRCC.

PBRM1

PBRM1 gene encodes BAF180 protein, which constitutes the PBAF complex and plays an important tumor suppressor role in the mechanism of chromatin remodeling. About 30%-40% of ccRCC patients carry PBRM1 mutations.  Therefore, the relationship between it and kidney cancer can be further studied, and its related clinical drugs can be developed.

SETD2

SETD2 encodes a methyltransferase that plays a major role in H3K36me3, and inactivation of SETD2 causes microsatellite instability. In the TCGA cohort, SETD2 mutations accounted for 13% of ccRCC cases. In addition, BAP1 and SETD2 mutations were highly prevalent in ccRCC patients with tumor thrombus.

BAP1

BAP1 encodes a histone deubiquitinating enzyme and is an essential chromatin regulator that functions as an inhibitor of cell proliferation. BAP1 mutations account for 5%-16% of ccRCC. BAP1 mutations were significantly more common in sarcomatoid RCC than in non-sarcomatoid RCC.

KDM5C

KDM5C encodes a member of the ARID protein family, which plays a role in the regulation of epigenetic modification. Studies have found that advanced renal cancer with KDM5C mutation has higher angiogenesis characteristics.

PTEN/PI3K/AKT/mTOR Pathway Genes

Alterations in the PI3K/AKT/mTOR pathway activate cell proliferation and angiogenesis. The genes related to this pathway mainly include PI3KCA, AKT, TSC1/2, mTOR and so on. The incidence of PI3KCA mutation in ccRCC is 3%~5%.

TP53

The mutation rate of TP53 in sarcomatoid RCC was high (42. 3%), which was correlated with sarcomatoid differentiation of ccRCC. In sarcomatoid RCC, TP53 mutations predict poor TKI, mTOR inhibitor response.

MET

MET mutations are predominantly found in pRCC. Among advanced pRCCs, 33% of type I pRCCs had MET mutations and 7% of type II pRCCs. MET mutations generally cause MET activation, so MET inhibitors can be used as therapeutic drugs of choice.

In addition to the above genes, there are interesting renal 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 renal 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 renal cancer tissues and cells, and is toxic to the body;
• The in vivo transfection system used cannot penetrate the renal 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 renal 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.

Reference

1. SUNG H, et al.; Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021, 71(3): 209-249.
2. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013, 499(7456):43-49.
3. VOSS MH, et al.; Genomically annotated risk model for advanced renal-cell carcinoma: a retrospective cohort study. Lancet Oncol. 2018,19(12): 1688-1698.
4. MOTZER RJ, et al.; Molecular subsets in renal cancer determine outcome to checkpoint and angiogenesis Blockade. Cancer Cell. 2020,38(6): 803-817. e4.
5. MALOUF GG, et al.; Genomic characterization of renal cell carcinoma with sarcomatoid dedifferentiation pinpoints recurrent genomic alterations. Eur Urol, 2016, 70(2):348-357.
6. PAL SK, et al.; Characterization of clinical cases of advanced papillary renal cell carcinoma via comprehensive genomic profiling. Eur Urol. 2018,73(1):71-78.
7. Miron B, et al.; Biomarker Development for Metastatic Renal Cell Carcinoma: Omics, Antigens, T-cells, and Beyond. J Pers Med. 2020, 10(4):225.

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