Liquid Biopsy Has Potential to Advance Precision Medicine in Melanoma

Precision medicine has opened the door to more personalized treatments in melanoma, improving the odds of survival for patients with advanced stage of the heterogenous disease. However, further improvements are still needed to offer improved efficacy to a greater number of patients.

According to researchers of a recent study published in the International Journal of Molecular Sciences, liquid biopsy—an increasingly popular tool across various cancers—may help unlock greater potential in melanoma.

Years of research has shown that in cancers like melanoma, liquid biopsy enables the detection of biomarkers, including:

• Circulating tumor cells (CTCs), which are released by the primary tumor or metastasis
• Circulating tumor DNA (ctDNA)—small fragments of nucleic acid released by CTCs
• Exomes, which are vesicles surrounded by plasma membrane and released by cells into microenvironment

Within melanoma, CTCs may be predictive of whether or not patient are responding to immunotherapy, with indications of a correlation between the cells and response to pembrolizumab in patients with advanced disease. According to the researchers, patients with PD-L1+ CTCs had superior progression-free survival (PFS) compared with patients with low levels of circulating PD-L1.

“The development of a signature of 19 genes for melanoma CTCs (CTC score) allowed to quickly assess the response to [immune checkpoint inhibitors]. CTCs score changes radically after treatment with immunotherapy, providing important information on the treatment response even in the long term,” explained the researchers. “Therefore, early monitoring of CTCs changes could help clinicians in screening patients for immunotherapy and it would also avoid unnecessary and harmful treatments for non-responsive patients.”

ctDNA is also being probed as a prognostic marker in melanoma. For example, in a sample of 48 patients with metastatic disease, researchers observed a “tight correlation” between early BRAF v600E ctDNA peak and having a complete response to treatment with TILs.

In a recent study, data suggested that ctDNA levels prior to receiving treatment can be used to stratify patients who receive first-line treatment with ICIs; patients with lower levels of ctDNA prior to treatment had favorable PFS.

In recent years, research has looked at the prognostic value of exomes, which may have potential due to their abundance in circulation.

“Tumor cells implement several mechanisms to evade the immune system control. One of these involves the release of exosomes that carry PDL1, still bound to the plasma membrane, into microenvironment,” wrote the researchers. “Consequently, the tumor enhances its immune evasive potential and develops resistance to ICIs treatments. Exosomal PDL1 can either antagonize anti-PD-L1 therapy by binding to the antibody itself or, being resistant to anti-PD-1 therapy, can suppress T-cell activity directly and/or indirectly.”

Reference

Valenti F, Falcone I, Ungania S, et al. Precision medicine and melanoma: multi-omics approaches to monitoring the immunotherapy response. Int J Mol Sci. 2021;22(8):3837.