TY - JOUR
T1 - Melanoma targeted therapies beyond braf-mutant melanoma
T2 - Potential druggable mutations and novel treatment approaches
AU - Khaddour, Karam
AU - Maahs, Lucas
AU - Avila-Rodriguez, Ana Maria
AU - Maamar, Yazan
AU - Samaan, Sami
AU - Ansstas, George
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Melanomas exhibit the highest rate of somatic mutations among all different types of cancers (with the exception of BCC and SCC). The accumulation of a multimode of mutations in the driver oncogenes are responsible for the proliferative, invasive, and aggressive nature of melanomas. High-resolution and high-throughput technology has led to the identification of distinct mutational signatures and their downstream alterations in several key pathways that contribute to melanomagenesis. This has enabled the development of individualized treatments by targeting specific molecular alterations that are vital for cancer cell survival, which has resulted in improved outcomes in several cancers, including melanomas. To date, BRAF and MEK inhibitors remain the only approved targeted therapy with a high level of evidence in BRAFV600E/K mutant melanomas. The lack of approved precision drugs in melanomas, relative to other cancers, despite harboring one of the highest rates of somatic mutations, advocates for further research to unveil effective therapeutics. In this review, we will discuss potential druggable mutations and the ongoing research of novel individualized treatment approaches targeting non-BRAF mutations in melanomas.
AB - Melanomas exhibit the highest rate of somatic mutations among all different types of cancers (with the exception of BCC and SCC). The accumulation of a multimode of mutations in the driver oncogenes are responsible for the proliferative, invasive, and aggressive nature of melanomas. High-resolution and high-throughput technology has led to the identification of distinct mutational signatures and their downstream alterations in several key pathways that contribute to melanomagenesis. This has enabled the development of individualized treatments by targeting specific molecular alterations that are vital for cancer cell survival, which has resulted in improved outcomes in several cancers, including melanomas. To date, BRAF and MEK inhibitors remain the only approved targeted therapy with a high level of evidence in BRAFV600E/K mutant melanomas. The lack of approved precision drugs in melanomas, relative to other cancers, despite harboring one of the highest rates of somatic mutations, advocates for further research to unveil effective therapeutics. In this review, we will discuss potential druggable mutations and the ongoing research of novel individualized treatment approaches targeting non-BRAF mutations in melanomas.
KW - BRAF
KW - DNA damage repair
KW - Epigenetic
KW - Ho-mologous recombination deficiency
KW - MEK
KW - Melanoma
KW - Molecular alteration
KW - NF1
KW - NRAS
KW - Precision oncology
KW - Targeted therapy
KW - Tumor suppressor gene
UR - http://www.scopus.com/inward/record.url?scp=85119583720&partnerID=8YFLogxK
U2 - 10.3390/cancers13225847
DO - 10.3390/cancers13225847
M3 - Review article
C2 - 34831002
AN - SCOPUS:85119583720
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 22
M1 - 5847
ER -