Gangliosides in Cutaneous Melanoma: Molecular Mechanisms, Translational Evidence Gaps, and Preclinical Natural-Compound Leads
7 affiliations
- 1Department of Biotechnology, College of Engineering, Daegu University, 201 Deagudae-ro, Jillyang, Gyeongsan 38453, Gyeongbuk, Republic of Korea
- 2Department of Biological Science, College of Health Sciences, Wonkwang University, 460 Iksan-daero, Iksan-si 54538, Jeonbuk, Republic of Korea
- 3Division of Biodrug Evaluation, New Drug Development Center, Osong Medical Innovation Foundation (K-12 Bio Health), Cheongju 28160, Chungbuk, Republic of Korea
- 4Futuristic Animal Resource & Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Chungbuk, Republic of Korea
- 5Department of Companion Animal Industry, Wonkwang University, 460 Iksan-daero, Iksan-si 54538, Jeonbuk, Republic of Korea
- 6Center for Animal Resources Development, Wonkwang University, 460 Iksan-daero, Iksan-si 54538, Jeonbuk, Republic of Korea
- 7Institute for Glycoscience, Wonkwang University, 460 Iksan-daero, Iksan-si 54538, Jeonbuk, Republic of Korea
Abstract
Cutaneous melanoma remains lethal once metastatic despite advances in immune checkpoint blockade and BRAF/MEK-directed therapy. Gangliosides are surface-accessible sialylated glycosphingolipids that regulate membrane organization, adhesion, and signaling, representing potential biomarkers and therapeutic targets. This narrative review evaluated the translational readiness of ganglioside-directed strategies in cutaneous melanoma, without assuming that evidence from other GD2- or GD3-positive cancers is directly transferable. We synthesized melanoma-specific evidence on GD3-linked focal adhesion signaling, p130Cas/paxillin activity, PI3K–AKT and MAPK outputs, and distinct phenotypes associated with GD3, GD2, and GM3. We then applied an evidence-gated framework distinguishing melanoma clinical evidence, melanoma preclinical evidence, cross-tumor translational evidence, and hypothesis-generating claims. Direct contemporary clinical evidence in melanoma remains limited. Antibody, cellular, and biosynthetic enzyme strategies require diagnostic-quality antigen profiling, demonstration of surface accessibility and functional dependency, and prospective monitoring for antigen escape and neurotoxicity. Natural compounds, particularly quercetin, are mechanistic probes or formulation-enabled leads: a 2024 study reported reduced GM3/GD3 abundance and FAK/paxillin/AKT signaling in melanoma cell lines, but high in vitro concentrations and the lack of pharmacokinetic or in vivo validation preclude therapeutic conclusions. We proposed a minimum evidence package and go/no-go criteria for clinical translation, specifying experiments needed to advance ganglioside biology into biomarker-defined melanoma interventions.
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BibTeX
@article{koo2026gangliosides,
title = {{Gangliosides in Cutaneous Melanoma: Molecular Mechanisms, Translational Evidence Gaps, and Preclinical Natural-Compound Leads}},
author = {Deog-Bon Koo and Kyongtae Kim and Juhwan Kim and Hyo Gyeong Yun and Eun Bin Song and Min Young Kim and Jae-Sung Ryu and Ji-Su Kim and Soyeon Kim and Hyun-A Lee and Young-Kug Choo},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209021},
url = {https://www.mdpi.com/1422-0067/27/20/9021},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Gangliosides in Cutaneous Melanoma: Molecular Mechanisms, Translational Evidence Gaps, and Preclinical Natural-Compound Leads
AU - Deog-Bon Koo
AU - Kyongtae Kim
AU - Juhwan Kim
AU - Hyo Gyeong Yun
AU - Eun Bin Song
AU - Min Young Kim
AU - Jae-Sung Ryu
AU - Ji-Su Kim
AU - Soyeon Kim
AU - Hyun-A Lee
AU - Young-Kug Choo
PY - 2026
DA - 2026/10/12
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209021
UR - https://www.mdpi.com/1422-0067/27/20/9021
AB - Cutaneous melanoma remains lethal once metastatic despite advances in immune checkpoint blockade and BRAF/MEK-directed therapy. Gangliosides are surface-accessible sialylated glycosphingolipids that regulate membrane organization, adhesion, and signaling, representing potential biomarkers and therapeutic targets. This narrative review evaluated the translational readiness of ganglioside-directed strategies in cutaneous melanoma, without assuming that evidence from other GD2- or GD3-positive cancers is directly transferable. We synthesized melanoma-specific evidence on GD3-linked focal adhesion signaling, p130Cas/paxillin activity, PI3K–AKT and MAPK outputs, and distinct phenotypes associated with GD3, GD2, and GM3. We then applied an evidence-gated framework distinguishing melanoma clinical evidence, melanoma preclinical evidence, cross-tumor translational evidence, and hypothesis-generating claims. Direct contemporary clinical evidence in melanoma remains limited. Antibody, cellular, and biosynthetic enzyme strategies require diagnostic-quality antigen profiling, demonstration of surface accessibility and functional dependency, and prospective monitoring for antigen escape and neurotoxicity. Natural compounds, particularly quercetin, are mechanistic probes or formulation-enabled leads: a 2024 study reported reduced GM3/GD3 abundance and FAK/paxillin/AKT signaling in melanoma cell lines, but high in vitro concentrations and the lack of pharmacokinetic or in vivo validation preclude therapeutic conclusions. We proposed a minimum evidence package and go/no-go criteria for clinical translation, specifying experiments needed to advance ganglioside biology into biomarker-defined melanoma interventions.
SN - 1422-0067
ER -