Melanoma brain metastases: Biological basis and novel therapeutic strategies

The development of brain metastases is the deadliest complication of advanced melanoma and has long been associated with a dismal prognosis. The recent years have seen incredible progress in the development of therapies for melanoma brain metastases (MBM), with both targeted therapies (the BRAF-MEK inhibitor combination) and immune checkpoint inhibitors (the anti-CTLA-4, anti-PD-1 combination) showing impressive levels of activity. Despite this, durations of response for these therapies remain lower at intracranial sites of metastasis compared to extracranial metastases and it has been suggested that there are unique features of the brain microenvironment that contribute to therapeutic escape. In this review, we outline the latest research into the biology and pathophysiology of melanoma brain metastasis development and progression. We then discuss the current status of clinical trial that are open to patients with MBM and end by describing the ongoing challenges for the field.

Automated summary

The development of brain metastases is the deadliest complication of advanced melanoma, and recent progress has been made in therapies for melanoma brain metastases (MBM). However, there are lower response durations for intracranial metastases compared to extracranial metastases, possibly due to unique features of the brain microenvironment. Current research focuses on the biology and pathophysiology of melanoma brain metastasis development, as well as the challenges faced in clinical trials and treatment for MBM patients.