TY - JOUR
T1 - New Approaches to Targeted Therapy in Melanoma
AU - Fernandez, Manuel Felipe
AU - Choi, Jacob
AU - Sosman, Jeffrey Alan
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/6
Y1 - 2023/6
N2 - It was just slightly more than a decade ago when metastatic melanoma carried a dismal prognosis with few, if any, effective therapies. Since then, the evolution of cancer immunotherapy has led to new and effective treatment approaches for melanoma. However, despite these advances, a sizable portion of patients with advanced melanoma have de novo or acquired resistance to immune checkpoint inhibitors. At the same time, therapies (BRAF plus MEK inhibitors) targeting the BRAFV600 mutations found in 40–50% of cutaneous melanomas have also been critical for optimizing management and improving patient outcomes. Even though immunotherapy has been established as the initial therapy in most patients with cutaneous melanoma, subsequent effective therapy is limited to BRAFV600 melanoma. For all other melanoma patients, driver mutations have not been effectively targeted. Numerous efforts are underway to target melanomas with NRAS mutations, NF-1 LOF mutations, and other genetic alterations leading to activation of the MAP kinase pathway. In this era of personalized medicine, we will review the current genetic landscape, molecular classifications, emerging drug targets, and the potential for combination therapies for non-BRAFV600 melanoma.
AB - It was just slightly more than a decade ago when metastatic melanoma carried a dismal prognosis with few, if any, effective therapies. Since then, the evolution of cancer immunotherapy has led to new and effective treatment approaches for melanoma. However, despite these advances, a sizable portion of patients with advanced melanoma have de novo or acquired resistance to immune checkpoint inhibitors. At the same time, therapies (BRAF plus MEK inhibitors) targeting the BRAFV600 mutations found in 40–50% of cutaneous melanomas have also been critical for optimizing management and improving patient outcomes. Even though immunotherapy has been established as the initial therapy in most patients with cutaneous melanoma, subsequent effective therapy is limited to BRAFV600 melanoma. For all other melanoma patients, driver mutations have not been effectively targeted. Numerous efforts are underway to target melanomas with NRAS mutations, NF-1 LOF mutations, and other genetic alterations leading to activation of the MAP kinase pathway. In this era of personalized medicine, we will review the current genetic landscape, molecular classifications, emerging drug targets, and the potential for combination therapies for non-BRAFV600 melanoma.
KW - BRAF
KW - MAPK pathway
KW - RAS
KW - melanoma
KW - targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85163960286&partnerID=8YFLogxK
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U2 - 10.3390/cancers15123224
DO - 10.3390/cancers15123224
M3 - Review article
C2 - 37370834
AN - SCOPUS:85163960286
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 12
M1 - 3224
ER -