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PI3K/AKT Pathway Potential Target for Treating Brain Mets in Melanoma

Laura Panjwani
Published: Monday, Apr 04, 2016

Michael Davies, MD

Michael Davies, MD

Activation of the PI3K/AKT pathway may play a role in the development of metastases in melanoma, according to a preclinical study published in Cell Report.1

, Davies discusses the biggest challenges in treating brain metastases, what is known about the connection to the PI3K/AKT pathway, and what his future plans are for research in this area.

OncLive: What are the biggest obstacles to treating brain metastases?

Davies: One of the very challenging things about the management of patients with brain metastases is, although there have been many exciting clinical trials over the last decade, patients with brain metastases have been excluded from almost all trials due to their poor outcomes and concern that many agents will not cross the blood-brain barrier.

Most other pathways do not look differentially activated. This suggests that the PI3K/AKT pathway plays a specific role in the pathogenesis of brain metastases and, therefore, may be a good therapeutic target to improve outcomes in patients.

What implications could a better understanding of the connection between PI3K/AKT and brain metastases have on future treatment strategies for patients with melanoma?

One of the things we hope to be able to do is actually identify which patients are at the highest risk for brain metastasis, even with early stages of disease. This could help us prioritize which patients actually need to be monitored, perhaps by an MRI of the brain, as part of their restaging workup after they’ve received potentially curative surgery.
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