TY - JOUR
T1 - Targeted therapy strategies for melanoma brain metastasis
AU - Saberian, Chantal
AU - Sperduto, Paul
AU - Davies, Michael A.
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Melanoma is the most aggressive of the common forms of skin cancer. Metastasis to the central nervous system is one of the most common and deadly complications of this disease. Historically, melanoma patients with brain metastases had a median survival of less than 6 months. However, outcomes of melanoma patients have markedly improved over the last decade due to new therapeutic approaches, including immune and targeted therapies. Targeted therapies leverage the high rate of driver mutations in this disease, which result in the activation of multiple key signaling pathways. The RAS-RAF-MEK-ERK pathway is activated in the majority of cutaneous melanomas, most commonly by point mutations in the Braf serine-threonine kinase. While most early targeted therapy studies excluded melanoma patients with brain metastases, subsequent studies have shown that BRAF inhibitors, now generally given concurrently with MEK inhibitors, achieve high rates of tumor response and disease control in Braf-mutant melanoma brain metastases (MBMs). Unfortunately, the duration of these responses is generally relatively short- and shorter than is observed in extracranial metastases. This review will summarize current data regarding the safety and efficacy of targeted therapies for MBMs and discuss rational combinatorial strategies that may improve outcomes further.
AB - Melanoma is the most aggressive of the common forms of skin cancer. Metastasis to the central nervous system is one of the most common and deadly complications of this disease. Historically, melanoma patients with brain metastases had a median survival of less than 6 months. However, outcomes of melanoma patients have markedly improved over the last decade due to new therapeutic approaches, including immune and targeted therapies. Targeted therapies leverage the high rate of driver mutations in this disease, which result in the activation of multiple key signaling pathways. The RAS-RAF-MEK-ERK pathway is activated in the majority of cutaneous melanomas, most commonly by point mutations in the Braf serine-threonine kinase. While most early targeted therapy studies excluded melanoma patients with brain metastases, subsequent studies have shown that BRAF inhibitors, now generally given concurrently with MEK inhibitors, achieve high rates of tumor response and disease control in Braf-mutant melanoma brain metastases (MBMs). Unfortunately, the duration of these responses is generally relatively short- and shorter than is observed in extracranial metastases. This review will summarize current data regarding the safety and efficacy of targeted therapies for MBMs and discuss rational combinatorial strategies that may improve outcomes further.
KW - brain metastasis
KW - melanoma
KW - targeted therapy
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U2 - 10.1093/noajnl/vdab131
DO - 10.1093/noajnl/vdab131
M3 - Article
C2 - 34859235
AN - SCOPUS:85147532172
SN - 2632-2498
VL - 3
SP - V75-V85
JO - Neuro-Oncology Advances
JF - Neuro-Oncology Advances
ER -