Melanoma

Melanoma is a rare but highly invasive form of skin cancer that can appear anywhere on the body. It most often occurs in sun-exposed areas such as the back, legs, arms, and face. Melanoma is one of the most likely malignancies to develop brain metastases, with approximately 6-11% of all brain metastases originating from melanoma. Once brain metastases occur, patients often have an extremely poor prognosis.

Figure 1. This is a schematic representation of melanoma cell invasion and metastasis formation in the brain. (Westphal, D., et al., 2017)

Brain metastases are extremely common in melanoma, and Alfa Cytology' solution has given researchers new insights into the genomics, immunology, and spatial organization of these tumors, and is the basis for further discovery and exploration of treatments.

Therapeutic targets

Melanoma brain metastases have more unstable chromosomes than melanoma metastases that have metastasized to other parts of the body. Chromosomal instability is the permanent gain and loss of larger chromosomal segments, a process that triggers signaling pathways that allow cells to spread more easily and better suppress the body's immune response. These signaling pathways may be important therapeutic targets, such as the PI3K/AKT pathway. Melanoma brain metastases show increased expression of the PI3K/AKT pathway compared to extracranial metastases. activating mutations in AKT or deletion of PTEN has an important role in invasion, cell migration, and adherent cell renewal.

Single-cell genetic analysis

We can perform single-cell genetic analysis on frozen tissue samples, allowing researchers to understand the biology of tumors and their microenvironment before they are altered by treatment.

Animal models

We can develop experimental models that accurately mimic human disease at the molecular and cellular level so that more effective therapeutic strategies can be developed to prevent, delay and treat melanoma brain metastases. These include immunodeficient and immunoreactive mouse models, chicken embryo models, adult zebrafish, and embryonic models.

Neoangiogenesis

Melanoma cells derive nutrients from healthy tissue through the process of neoangiogenesis. Several studies have shown that the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in this process and that STAT3 shows sustained activation in brain metastases compared to the primary tissue.

Immunotherapy

• High dose (HD) interleukin 2 (IL-2). Cytokine-based immunotherapy.
• Checkpoint inhibitors. Uses antibodies against specific suppressive T cell molecules to increase the magnitude and duration of T cell responses.
• Anti-PD-1 immunotherapy.

The treatment of melanoma brain metastases is an unmet need and its animal models have become an integral part of overcoming many challenges as they offer the possibility of translating important discoveries into therapy. As meaningful discoveries emerge, we will support you in using in vivo models to validate the findings. Modern targeted therapies and immunotherapies will continue to be tested in vivo, followed by their efficacy against brain metastases in broader, more complex, and relevant animal models. Alfa Cytology aims to better help you understand chemokine signaling, cell arrest in the brain microvascular system, extravasation, and vascular co-selection to reveal the potential to promote brain tropism and potentially reveal therapeutic molecules important for intervening in new targets. Please feel free to contact us to find out more about what we can do for you.

Reference

1. Westphal, D., et al. (2017). "Molecular insights into melanoma brain metastases." Cancer, 123: 2163-2175.