Liquid Biopsy: Value for Melanoma Therapy?

Buder‐Bakhaya, Kristina; Machiraju, Devayani; Hassel, Jessica C.

doi:10.1159/000478893

Cited by 9 publications

(8 citation statements)

References 47 publications

(62 reference statements)

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“…Liquid biopsy, including CTCs, ctDNA, and circulating tumor RNA (ctRNA) has only been studied in small patient cohorts treated by use of ICI (mainly CTLA4ab) for melanoma. An association between treatment response and a decrease in CTCs and ctDNA has been found for targeted therapy, but not for ICI ( 94 ). Methodological improvements offer new opportunities for CTC detection, as has been very recently described for microfluidic enrichment of melanoma CTCs combined with RNA-based droplet digital PCR quantitation ( 64 ).…”

Section: Blood Biomarkersmentioning

confidence: 99%

Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment—A Review From the Melanoma Perspective and Beyond

2018

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BackgroundImmune checkpoint inhibition (ICI) with anti-CTLA-4 and/or anti-PD-1 antibodies is standard treatment for metastatic melanoma. Anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for treatment of several other advanced malignancies, including non-small-cell lung cancer (NSCLC); renal cell, and urothelial carcinoma; head and neck cancer; gastric, hepatocellular, and Merkel-cell carcinoma; and classical Hodgkin lymphoma. In some of these malignancies approval was based on the detection of biomarkers such as PD-L1 expression or high microsatellite instability.MethodsWe review the current status of prognostic and predictive biomarkers used in ICI for melanoma and other malignancies. We include clinical, tissue, blood, and stool biomarkers, as well as imaging biomarkers.ResultsSeveral biomarkers have been studied in ICI for metastatic melanoma. In clinical practice, pre-treatment tumor burden measured by means of imaging and serum lactate dehydrogenase level is already being used to estimate the likelihood of effective ICI treatment. In peripheral blood, the number of different immune cell types, such as lymphocytes, neutrophils, and eosinophils, as well as different soluble factors, have been correlated with clinical outcome. For intra-tumoral biomarkers, expression of the PD-1 ligand PD-L1 has been found to be of some predictive value for anti-PD-1-directed therapy for NSCLC and melanoma. A high mutational load, particularly when accompanied by neoantigens, seems to facilitate immune response and correlates with patient survival for all entities treated by use of ICI. Tumor microenvironment also seems to be of major importance. Interestingly, even the gut microbiome has been found to correlate with response to ICI, most likely through immuno-stimulatory effects of distinct bacteria. New imaging biomarkers, e.g., for PET, and magnetic resonance imaging are also being investigated, and results suggest they will make early prediction of patient response possible.ConclusionSeveral promising results are available regarding possible biomarkers for response to ICI, which need to be validated in large clinical trials. A better understanding of how ICI works will enable the development of biomarkers that can predict the response of individual patients.

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Section: Blood Biomarkersmentioning

confidence: 99%

Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment—A Review From the Melanoma Perspective and Beyond

2018

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“…The most frequent and explored alterations are BRAF and NRAS mutations, present in 40–60% and 28% of patients, respectively 24 , 25 . In addition, a high frequency of mutations in the promoter region of TERT gene has been found in melanoma patients with a frequency ranging from 50 to 80% in several studies 24 , 26 , 27 , including Brazilian populations 28 .…”

Section: Introductionmentioning

confidence: 99%

Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients

Marczynski

Laus

Reis

et al. 2020

Sci Rep

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BRAF, NRAS and TERT mutations occur in more than 2/3 of melanomas. Its detection in patient’s blood, as circulating tumor DNA (ctDNA), represents a possibility for identification and monitoring of metastatic disease. We proposed to standardize a liquid biopsy platform to identify hotspot mutations in BRAF, NRAS and TERT in plasma samples from advanced melanoma patients and investigate whether it was associated to clinical outcome. Firstly, we performed digital polymerase chain reaction using tumor cell lines for validation and determination of limit of detection (LOD) of each assay and screened plasma samples from healthy individuals to determine the limit of blank (LOB). Then, we selected 19 stage III and IV patients and determined the somatic mutations status in tumor tissue and track them in patients’ plasma. We established a specific and sensitive methodology with a LOD ranging from 0.13 to 0.37%, and LOB ranging from of 0 to 5.201 copies/reaction. Somatic mutations occurred in 17/19 (89%) patients, of whom seven (41%) had ctDNA detectable their paired plasma. ctDNA detection was associated with shorter progression free survival (p = 0.01). In conclusion, our data support the use of ctDNA as prognosis biomarker, suggesting that patients with detectable levels have an unfavorable outcome.

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“…Among the many biomarkers used in melanoma, ctDNA is already considered a valuable tool for monitoring the therapy response [44][45][46]. For instance, it has been shown that the increase of ctDNA level in the plasma of patients with BRAF-mutated melanoma treated with targeted therapies precedes the detection of relapses by imaging and by clinical evaluation [47].…”

Section: Circulating Tumor Dnamentioning

confidence: 99%

Clinical Relevance of Liquid Biopsy in Melanoma and Merkel Cell Carcinoma

Boyer¹,

Cayrefourcq²,

Dereure

et al. 2020

Cancers

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Melanoma and Merkel cell carcinoma are two aggressive skin malignancies with high disease-related mortality and increasing incidence rates. Currently, invasive tumor tissue biopsy is the gold standard for their diagnosis, and no reliable easily accessible biomarker is available to monitor patients with melanoma or Merkel cell carcinoma during the disease course. In these last years, liquid biopsy has emerged as a candidate approach to overcome this limit and to identify biomarkers for early cancer diagnosis, prognosis, therapeutic response prediction, and patient follow-up. Liquid biopsy is a blood-based non-invasive procedure that allows the sequential analysis of circulating tumor cells, circulating cell-free and tumor DNA, and extracellular vesicles. These innovative biosources show similar features as the primary tumor from where they originated and represent an alternative to invasive solid tumor biopsy. In this review, the biology and technical challenges linked to the detection and analysis of the different circulating candidate biomarkers for melanoma and Merkel cell carcinoma are discussed as well as their clinical relevance.

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Liquid Biopsy: Value for Melanoma Therapy?

Cited by 9 publications

References 47 publications

Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment—A Review From the Melanoma Perspective and Beyond

Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment—A Review From the Melanoma Perspective and Beyond

Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients

Clinical Relevance of Liquid Biopsy in Melanoma and Merkel Cell Carcinoma

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