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Updated: Dec 7, 2025
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Drug tolerance to target therapy in melanoma revealed at single cell level: What next?
Domenico Liguoro1, Luigi Fattore2, Rita Mancini1
1Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, 00161 Rome, Italy.
Abstract:
Drug resistance strongly impairs the efficacy of virtually every kind of anticancer therapy. This phenomenon is commonly fueled by intrinsic or acquired mechanisms. In this mini-review, focusing on BRAF-mutated melanoma as prototypical example, we analyze how recent studies that make use of single cell analysis identify the involvement of distinct transcriptional trajectories as the common thread at the basis of drug tolerance. The identification of these transcriptional trajectories provide a mechanistic basis for the development of both intrinsic and acquired drug resistance. These studies also suggest that hitting these transcriptional trajectories through personalized adaptive treatments can delay or abrogate the onset of drug resistance.
Insights
Drug resistance in cancer is often driven by distinct transcriptional trajectories. Targeting these pathways with personalized treatments may overcome or delay drug resistance, improving anticancer therapy efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Drug resistance significantly limits the effectiveness of cancer therapies.
- Mechanisms of drug resistance can be intrinsic or acquired.
- BRAF-mutated melanoma serves as a key model for studying drug resistance.
Purpose of the Study:
- To review recent findings on transcriptional trajectories in drug tolerance.
- To understand the role of single-cell analysis in identifying resistance mechanisms.
- To explore therapeutic strategies targeting transcriptional pathways.
Main Methods:
- Review of recent scientific literature.
- Analysis of studies utilizing single-cell analysis techniques.
- Focus on BRAF-mutated melanoma models.
Main Results:
- Single-cell analysis reveals distinct transcriptional trajectories in drug-tolerant cells.
- These trajectories provide a mechanistic explanation for intrinsic and acquired drug resistance.
- Identification of specific pathways involved in melanoma drug tolerance.
Conclusions:
- Transcriptional trajectories are central to drug tolerance and resistance in cancer.
- Personalized adaptive treatments targeting these trajectories show promise.
- Strategies aimed at these pathways could delay or prevent the development of drug resistance.
