A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients

Bustos, Matías A.; Gross, Rebecca; Rahimzadeh, Negin; Cole, Hunter; Tran, Linh Thanh; Tran, Kevin; Takeshima, Ling; Stern, Stacey L.; O’Day, Steven; Hoon, Dave S. B.

doi:10.3390/cancers12113361

Cited by 27 publications

(20 citation statements)

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“…In regards to the miRNA content, authors found some miRNAs enriched in the EVs from non-responding patients, such as miR-551a; in contrast, other miRNAs such as miR-4519 and miR-4674 were enriched in the EVs derived from responding patients ( 49 ). Finally, a pilot study identified a signature composed of three circulating miRNAs, namely miR-4649-3p, miR-615-3p and miR-1234-3p as potentially capable of distinguishing melanoma patients who better respond to immunotherapy (ipilimumab, nivolumab, pembrolizumab, or the combination of ipilimumab and nivolumab as first line therapy) ( 50 ). In particular, the levels of these miRNAs significantly decreased in the post-treatment samples derived from patients who had a complete response (CR) as compared to patients who progressed from immunotherapy.…”

Section: Non Coding Rnas (Ncrnas)mentioning

confidence: 99%

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The Promise of Liquid Biopsy to Predict Response to Immunotherapy in Metastatic Melanoma

et al. 2021

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Metastatic melanoma is the deadliest form of skin cancer whose incidence has been rising dramatically over the last few decades. Nowadays, the most successful approach in treating advanced melanoma is immunotherapy which encompasses the use of immune checkpoint blockers able to unleash the immune system’s activity against tumor cells. Immunotherapy has dramatically changed clinical practice by contributing to increasing long term overall survival. Despite these striking therapeutic effects, the clinical benefits are strongly mitigated by innate or acquired resistance. In this context, it is of utmost importance to develop methods capable of predicting patient response to immunotherapy. To this purpose, one major step forward may be provided by measuring non-invasive biomarkers in human fluids, namely Liquid Biopsies (LBs). Several LB approaches have been developed over the last few years thanks to technological breakthroughs that have allowed to evaluate circulating components also when they are present in low abundance. The elements of this so-called “circulome” mostly encompass: tumor DNA, tumor and immune cells, soluble factors and non-coding RNAs. Here, we review the current knowledge of these molecules as predictors of response to immunotherapy in metastatic melanoma and predict that LB will soon enter into routine practice in order to guide clinical decisions for cancer immunotherapy.

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Section: Non Coding Rnas (Ncrnas)mentioning

confidence: 99%

“…Interestingly, the increased levels of one of these miRNA, i.e. miR-615-3p showed a superior statistic capability in predicting PD in post-therapy plasma samples as compared to LDH levels ( 50 ).…”

Section: Non Coding Rnas (Ncrnas)mentioning

confidence: 99%

The Promise of Liquid Biopsy to Predict Response to Immunotherapy in Metastatic Melanoma

et al. 2021

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“…Similarly, other studies have proposed the analysis of the methylation of several genes in plasma as circulating epigenetic biomarkers able to discriminate between healthy controls and patients with AA or CRC [ 165 , 166 ]. In addition, approaches based on methylation microarrays [ 33 ] and NGS [ 167 ] have been used to identify epigenetic biomarkers in ctDNA for cancer detection.…”

Section: Epigenetic Biomarkers In Colorectal Cancermentioning

confidence: 99%

“…Besides, the detection of hypermethylated RASSF1A in serum before treatment was able to predict the prognosis and clinical response to drugs in advanced melanoma patients [ 185 ]. In a recent pilot study using NGS and machine learning, Bustos et al were able to identify a circulating miRNA signature (miR-4649-3p, miR-615-3p, and miR-1234-3p) associated with the response to ICIs in advanced melanoma patients, suggesting that circulating miRNAs could enable real-time monitoring of patients receiving this type of treatment [ 167 ]. The plasmatic levels of other ncRNAs such as lncRNAs (IGF2AS, anti-Peg11, MEG3, Zeb2NAT) were also found to be associated with prognosis and therapy response in BRAF -mutant advanced melanoma patients treated with the BRAF inhibitor vemurafenib [ 186 ].…”

Section: Epigenetic Biomarkers In Other Tumor Types and Multi-cancer Testsmentioning

confidence: 99%

Cancer Epigenetic Biomarkers in Liquid Biopsy for High Incidence Malignancies

Palanca-Ballester

Rodríguez‐Casanova

Torres

et al. 2021

Cancers

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Early alterations in cancer include the deregulation of epigenetic events such as changes in DNA methylation and abnormal levels of non-coding (nc)RNAs. Although these changes can be identified in tumors, alternative sources of samples may offer advantages over tissue biopsies. Because tumors shed DNA, RNA, and proteins, biological fluids containing these molecules can accurately reflect alterations found in cancer cells, not only coming from the primary tumor, but also from metastasis and from the tumor microenvironment (TME). Depending on the type of cancer, biological fluids encompass blood, urine, cerebrospinal fluid, and saliva, among others. Such samples are named with the general term “liquid biopsy” (LB). With the advent of ultrasensitive technologies during the last decade, the identification of actionable genetic alterations (i.e., mutations) in LB is a common practice to decide whether or not targeted therapy should be applied. Likewise, the analysis of global or specific epigenetic alterations may also be important as biomarkers for diagnosis, prognosis, and even for cancer drug response. Several commercial kits that assess the DNA promoter methylation of single genes or gene sets are available, with some of them being tested as biomarkers for diagnosis in clinical trials. From the tumors with highest incidence, we can stress the relevance of DNA methylation changes in the following genes found in LB: SHOX2 (for lung cancer); RASSF1A, RARB2, and GSTP1 (for lung, breast, genitourinary and colon cancers); and SEPT9 (for colon cancer). Moreover, multi-cancer high-throughput methylation-based tests are now commercially available. Increased levels of the microRNA miR21 and several miRNA- and long ncRNA-signatures can also be indicative biomarkers in LB. Therefore, epigenetic biomarkers are attractive and may have a clinical value in cancer. Nonetheless, validation, standardization, and demonstration of an added value over the common clinical practice are issues needed to be addressed in the transfer of this knowledge from “bench to bedside”.

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“…In comparison to PCR, NGS requires no specific assay to determine if sarcoma-associated genes are present in clinical material. Analyses using NGS may be unbiased and genome-wide or instead focussed on panels of known oncogenes either as an oncogene-focussed adaptation of standard NGS (FusionPlex (Archer) [ 116 ] or AmpliSeq Focus panel (Illumina) [ 117 ]) or variations based on nuclease protection chemistry (Edgeseq (HTG) [ 118 ]).…”

Section: Liquid Biopsy For Sarcoma Surveillancementioning

confidence: 99%

Rationale for Early Detection of EWSR1 Translocation-Associated Sarcoma Biomarkers in Liquid Biopsy

Clanchy

2021

Cancers

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Sarcomas are mesenchymal tumours that often arise and develop as a result of chromosomal translocations, and for several forms of sarcoma the EWSR1 gene is a frequent translocation partner. Sarcomas are a rare form of malignancy, which arguably have a proportionally greater societal burden that their prevalence would suggest, as they are more common in young people, with survivors prone to lifelong disability. For most forms of sarcoma, histological diagnosis is confirmed by molecular techniques such as FISH or RT-PCR. Surveillance after surgical excision, or ablation by radiation or chemotherapy, has remained relatively unchanged for decades, but recent developments in molecular biology have accelerated the progress towards routine analysis of liquid biopsies of peripheral blood. The potential to detect evidence of residual disease or metastasis in the blood has been demonstrated by several groups but remains unrealized as a routine diagnostic for relapse during remission, for disease monitoring during treatment, and for the detection of occult, residual disease at the end of therapy. An update is provided on research relevant to the improvement of the early detection of relapse in sarcomas with EWSR1-associated translocations, in the contexts of biology, diagnosis, and liquid biopsy.

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A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients

Cited by 27 publications

References 50 publications

The Promise of Liquid Biopsy to Predict Response to Immunotherapy in Metastatic Melanoma

The Promise of Liquid Biopsy to Predict Response to Immunotherapy in Metastatic Melanoma

Cancer Epigenetic Biomarkers in Liquid Biopsy for High Incidence Malignancies

Rationale for Early Detection of EWSR1 Translocation-Associated Sarcoma Biomarkers in Liquid Biopsy

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