Renal Cell Carcinoma

Early-stage renal cell carcinoma (RCC) is usually small and the disease is not very serious, so the cancer cells do not usually spread and metastasize to other areas. As the disease continues to progress and RCC advances to an advanced stage, spread and metastasis to other sites will occur. About 30-40% of RCC eventually metastasizes, with 5% of these being brain metastases. Brain metastases are the earliest site of metastasis in about 12% of RCC that develops. The prognosis for RCC brain metastases (RCCBM) is worse than for metastases from other sites, with a median survival of only 3-4 months for untreated patients.

Figure 1. The heterogeneous tumor microenvironment of the RCC brain metastases. (Loren, I., et al., 2021)

Systemic treatment with targeted drugs for RCCBM has so far proved relatively ineffective, and immunotherapy has shown little benefit. Many drugs that are effective outside the brain are not effective against brain metastases. Alfa Cytology offers solutions for those in the RCCBM research field through our existing platform, and we are committed to helping you make a breakthrough in the field by focusing on the depth and feasibility of y research.

Tyrosine kinase inhibitors (TKI)

TKIs exert anti-tumour effects by targeting and inhibiting MET, VEGFR2, and RET signaling pathways, killing tumor cells, reducing metastasis, and inhibiting angiogenesis.

Immune checkpoint inhibitors (ICI)

• Anti-programmed death 1 (PD-1)/PD-ligand1 (PD-L1)
  PD1/PDL1-targeted ICIs enhance the ability of the autoimmune system to combat the immune escape of tumor cells by blocking this signaling pathway.
• Cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor
  CTLA-4 plays an essential regulatory role in the activation of T cells and is a cytotoxic T lymphocyte-associated protein expressed on the surface of T cells. When it binds to B7-1 (CD80) and B7-2 (CD86) on the surface of antigen-presenting cells (APCs), it competitively inhibits the binding of B7 to CD28 on the surface of T cells, thereby inhibiting the activation process of T cells. Thus inhibition of CTLA-4 by inhibitory antibodies can block this mechanism and thus enhance T cell activity.

Epigenetic regulation

Metabolic and epigenetic modifications are one of the key features of RCC. Genes such as BAP1 and PBRM1, which are frequently mutated, are mainly involved in important epigenetic events such as histone modification mechanisms and chromatin remodeling. Aberrant epigenetic control leading to gene expression is becoming a contributing factor to the development, progression, and metastatic spread of RCC.

The reasons for the paucity of clinical studies of RCCBM include the lower probability of brain metastases compared to other distant metastases, the poor prognosis of patients, and the riskiness of treatment. The treatments currently available have all shown some therapeutic potential, but the risks cannot be ignored. The adverse effects of targeted drugs as well as immunological drugs are dominated by fatigue, fatigue, and rash, while stereotactic radiotherapy may trigger the risk of brain edema in the treated area. In the current situation, Alfa Cytology is still doing its best to provide researchers in this field with solutions to maximize the prognosis of RCCBM and avoid treatment-related adverse effects. Please feel free to contact our staff for more information on the latest solutions.

Reference

1.  Loren, I., et al. (2021). "Challenges and advances for the treatment of renal cancer patients with brain metastases: From immunological background to upcoming clinical evidence on immune-checkpoint inhibitors." Critical Reviews in Oncology/Hematology, 163: 103390.