Target intelligence / Profile preview

Melanoma stem cell (MSC)

Target
MSC
Molecular classification
Other
01

Overview

Melanoma stem cells (MSCs), also referred to as melanoma-initiating cells (MICs), are a subpopulation of melanoma cells defined by their capacity for self-renewal, multi-lineage differentiation, and the ability to initiate and maintain tumor growth (Schatton et al., 2008, Nature). These cells are typically identified through markers such as CD271 (p75NTR), ABCB5, and CD133, which are associated with increased tumorigenicity and metastatic potential (Boiko et al., 2010, Nature; Monzani et al., 2007, Eur J Cancer). MSCs are notably resistant to standard therapies, including chemotherapy and BRAF/MEK inhibitors, which often leads to disease relapse after initial treatment response (Roesch et al., 2010, Cell). Therapeutic approaches targeting MSCs focus on inhibiting conserved developmental pathways like Wnt, Notch, and Hedgehog, or using monoclonal antibodies against surface markers (Santini et al., 2012, Stem Cells). A major challenge in targeting MSCs is the high degree of phenotypic plasticity, where non-stem melanoma cells can revert to a stem-like state in response to environmental cues or therapy (Quintana et al., 2010, Cancer Cell).

Other names
Melanoma-initiating cellMICMelanoma cancer stem cellMelanoma CSC
02

Mechanism of action

Targeting of specific cell-surface markers or inhibition of developmental signaling pathways (Wnt, Notch, Hedgehog) to deplete the self-renewing subpopulation.

03

Biological functions

Cell proliferationOther
04

Disease associations

Cancer
05

Safety considerations

Off-target toxicity to normal neural crest-derived stem cellsPhenotypic plasticity allowing non-stem cells to acquire stem-like propertiesIntratumoral heterogeneity and marker instability
06

Interacting drugs

ABCB5 monoclonal antibodies

3 more in the full profile.

07

Biomarkers

CD271 (p75NTR)ABCB5CD133ALDH1A1JARID1B

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