Phenotypic tumour cell plasticity as a resistance mechanism and therapeutic target in melanoma

Area of Science:

• Oncology
• Cancer Biology
• Immunology

Background:

• Advanced melanoma treatments, including MAPK inhibitors and immune checkpoint inhibitors, show success but face intrinsic and acquired resistance.
• Therapy resistance in melanoma is influenced by genetic evolution and epigenetically driven adaptive plasticity.

Purpose of the Study:

• To review the dynamic interconversion and overlap between different melanoma cell phenotypes.
• To explore the role of these phenotypes in the context of therapy resistance and the tumor microenvironment.

Main Methods:

• Literature review focusing on melanoma cell plasticity.
• Analysis of adaptive mechanisms in response to therapeutic stress.
• Examination of the interplay between melanoma phenotypes and the microenvironment.

Main Results:

• Melanoma cells exhibit dynamic shifts in transcriptional programs, cell cycle states, and differentiation phenotypes.
• Epigenetic plasticity allows melanoma cells to adapt to stressors like immune attack and cancer therapies.
• Phenotypic interconversion contributes significantly to both intrinsic and acquired therapy resistance.

Conclusions:

• Melanoma therapy resistance is a complex process involving dynamic cellular adaptation beyond genetic mutations.
• Targeting epigenetic plasticity and understanding phenotypic plasticity are crucial for improving melanoma treatment efficacy.