Prognostic biomarkers in melanoma: a 2023 update from clinical trials in different therapeutic scenarios

ABSTRACT

Introduction

Over the past decade, significant advancements in the field of melanoma have included the introduction of a new staging system and the development of immunotherapy and targeted therapies, leading to changes in substage classification and impacting patient prognosis. Despite these strides, early detection remains paramount. The quest for dependable prognostic biomarkers is ongoing, given melanoma’s unpredictable nature, especially in identifying patients at risk of relapse. Reliable biomarkers are critical for informed treatment decisions.

Areas covered

This review offers a comprehensive review of prognostic biomarkers in the context of clinical trials for immunotherapy and targeted therapy. It explores different clinical scenarios, including adjuvant, metastatic, and neo-adjuvant settings. Key findings suggest that tumor mutational burden, PD-L1 expression, IFN-γ signature, and immune-related factors are promising biomarkers associated with improved treatment responses.

Expert opinion

Identifying practical prognostic factors for melanoma therapy is challenging due to the tumor’s heterogeneity. Promising biomarkers include tumor mutational burden (TMB), circulating tumor DNA, and those characterizing the tumor microenvironment, especially the immune component. Future research should prioritize large-scale, prospective studies to validate and standardize these biomarkers, emphasizing clinical relevance and real-world applicability. Easily accessible biomarkers have the potential to enhance the precision and effectiveness of melanoma management.

KEYWORDS:

• Melanoma
• biomarker
• prognosis
• mRNA
• gene expression profile
• target therapy
• BRAF
• immunotherapy

Article highlights

• Melanoma management has undergone a transformative shift with targeted therapy and immunotherapy, highlighting the critical need for validated prognostic biomarkers.

• Biomarker investigations in melanoma have extended beyond metastatic and adjuvant settings, with recent insights emerging from studies focused on neo-adjuvant therapy.

• Promising biomarkers, including tumor mutational burden, PD-L1 expression, IFN-γ signature, and immune-related factors, are linked to improved treatment responses in melanoma.

• The translation of these promising biomarker findings from clinical trials into real-life scenarios necessitates thorough validation.

• Validating these discoveries in real-world settings will strengthen their practical applicability and enhance their significance in guiding personalized melanoma treatment strategies.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This project was partially funded by the Research Projects of National Relevant Interest, Prot.20209KY3Y7.