Completed Cancer Genetics & Molecular Biology

Gene-drug interactions in the melanocyte lineage and melanoma

Funder MRC (part of UKRI)
Recipient organisation University of Edinburgh
Funding £3.1M
Period Mar 2018 — Mar 2023

In plain English

AI plain-English summary

Melanoma cells that survive initial treatment are the target of a new drug-screening effort using genetically engineered zebrafish. Melanoma is the deadliest form of skin cancer, and its incidence is rising rapidly in the UK and Europe. While recent therapies often shrink tumours, the cancer returns in most patients because some cells within the melanoma resist treatment. The researchers have built a zebrafish model that develops melanomas closely resembling human ones. This system is unique in allowing them to image different cell types within a living tumour, screen drugs in real time, and track how individual cells respond to treatment. If successful, the work could identify drug targets that, when combined with existing therapies, kill the resistant cells and prevent relapse. This is fundamental science—the immediate output is a deeper understanding of how melanoma cells evade treatment, not a new drug ready for the clinic. However, similar fundamental work on tumour heterogeneity has previously revealed vulnerabilities that led to targeted therapies for other cancers. The zebrafish model itself could become a platform for testing future drug combinations.

View original technical description
The aim of our work is to discover new therapeutic approaches and drug targets for melanoma. Melanoma is the most deadly form of skin cancer, and incidence continues to rise rapidly in the UK and Europe. Recent advances in melanoma therapy often lead to regression of the cancer, but for most patients, the melanoma comes back. This suggests that while therapies can kill most of the cancer, there are some cells in the melanoma that are resistant to therapy. Our goal is to identify these different cells within melanoma, and develop new therapeutic approaches that can be used in combination with current therapy to eradicate the tumour. We have developed a model system that enables us to genetically engineer zebrafish to develop melanomas that are similar to human melanomas. We use these animals to image the different cell types within melanoma, to screen for new drugs, and follow how the different cell populations within the cancers respond to new drugs at the single cell level. There are no other animal systems that allow us to do these studies at this resolution. We hope that these studies will help us to better understand how melanoma responds to drug treatment, and identify new vulnerabilities that we can use to target melanoma.

View the original record at the funder ↗

Researchers

Elizabeth Patton (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Targeting developmental cell states in melanoma
Chemical Biology in Zebrafish: Drug-Leads and New Targets in the Melanocyte Lineage and Melanoma
A chemical genetic approach to identify pharmacological targets co-operating with melanoma drivers and their validation as combinatorial therapeutic targets
Contribution of autophagy to the maintenance, invasion and metastasis of melanoma stem-like sub populations.
Molecular Oncology Group

Original classification

Intramural

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.