Melanoma is the fifth most common type of cancer and the most frequent among the young adult population in Europe. Immunotherapy has greatly improved survival for advanced melanoma, but almost half of melanoma patients still lose their lives to cancer.

Melanoma is at the cutting edge of novel immuno-oncology strategies such as checkpoint inhibitors, tebentafusp (first-in-class bispecific molecule), as well as adoptive cell therapy. But we still don't fully understand the mechanisms behind resistance and when they occur during tumour progression, although we know they develop numerous ways of hiding from the immune system or reducing its activity.

The melanoma programme leverages multiple large scale multi-omic translational projects to explore mechanisms of response and resistance to immunotherapy, tumour evolution and biomarker discovery.

An illustration of the studies that track melanomas

Figure 1: The clinical course of melanoma and related research efforts.
Primary melanoma diagnosis and excision, excision of melanoma at an advanced stage, metastatic disease and systemic therapy, treatment resistance and disease progression, death. 

PEACE Melanoma involves multiregional sampling at post-mortem and multi-omic profiling to study tumour evolution and mechanisms of immunotherapy resistance.

TRACERx Melanoma focuses on the mechanisms of immunotherapy response and resistance, biomarker discovery, and longitudinal sampling (surgery, biopsies, blood samples).

PEACE Melanoma

PEACE is a national post-mortem program that enables extensive sampling of melanoma metastases, providing a unique opportunity to study the evolution of melanoma over time.

By combining post-mortem samples with those collected during life, the study offers critical insights into treatment resistance. Our recent publication, Late-stage metastatic melanoma emerges through a diversity of evolutionary pathways, demonstrated the heterogeneity of advanced melanoma and identified various pathways to resistance and immune evasion.

Our future work within PEACE Melanoma entails a uveal melanoma cohort, a rare and molecularly distinct type of melanoma, as well as an expansion cohort to build upon these insights

Clinical Study Identifier: NCT03004755

TRACERx Melanoma

TRACERx Melanoma complements PEACE by tracking patients across different stages and treatments, with longitudinal sampling of surgical, biopsy, and blood specimens, and detailed clinical annotations.

This approach, along with data from large cohorts like the 100,000 Genomes Project, aims to address critical gaps in understanding melanoma, particularly concerning mechanisms of response and resistance to immunotherapy in metastatic and adjuvant settings alongside with biomarker discovery.

For more information about the study, please visit Cancer Research UK.

Funding

  • Melanoma Research Alliance
  • Rosetrees foundation
  • Royal Marsden Cancer Charity (significant donations from Ross-Russell Family, MacFarlanes LLP and Shiona Ramage)
  • McAlpine Foundation
  • Melanoma UK
  • Bjorn Saven foundation

Publications