Current and Emerging Utility of Liquid Biopsy in Cancers. More than Surrogate Biomarkers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 21309

Special Issue Editors


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Guest Editor
Molecular and Translational Oncology Unit, Department of Biomedical Innovation at CIEMAT, Madrid, Spain
Interests: liquid biopsy and tumor cells biomarkers in genitourinary tumors
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Gastrointestinal Tumor Group, Department of Oncology, Vall d’Hebron Institute of Oncology, Barcelona, Spain
Interests: the use of liquid biopsy in cancer research and clinical application

Special Issue Information

Dear Colleagues,

Liquid biopsy has emerged as a reliable tool for tumor surveillance, studying disseminated tumor cells in bone marrow and circulating tumor cells in peripheral blood and providing crucial insights into cancer biology and the metastatic process. More recently, the development of the detection and characterization of circulating tumor DNA (ctDNA) and other molecules either free or as extracellular vessels has finally enabled the arrival of liquid biopsy assays into clinical practice; however, little is known about the circulating tumor microenvironment either at the cellular or biomarker level and its potential implementation to help define the best molecularly targeted therapies for cancer. In this context, this Special Issue will focus on the next frontier for the clinical application of liquid biopsy in cancer treatment, cancer screening, diagnosis, follow-up, and the best personalized therapies as potential future applications. We would like to develop a compendium issue centered in technology, methodologies, and logistics for the eventual integration of liquid biopsy into the clinical workflow.

We are pleased to invite you to participate in this Special Issue that will focus on the state of the art and the latest findings on circulating tumor biomarkers, circulating tumor cells (CTCs), tumor hybrid cells (THCs), as well as ctDNA and ctRNA (coding and noncoding) and protein analysis, and clinical evidence regarding the implementation of liquid biopsy in clinical practice.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Implication of liquid biopsy in cancer diagnosis, prognosis, and clinical management;
  • More than circulating tumor cells in blood sample characterization;
  • DNAs, RNAs, and proteins as cancer biomarkers in biofluids;
  • Liquid biopsy approximations in immunotherapy response prediction.

We look forward to receiving your contributions.

Dr. Marta Dueñas
Dr. Rodrigo Toledo
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • liquid biopsy
  • ctDNA
  • ctRNA
  • cytokine profiling
  • tumor biomarkers
  • CTC
  • THC

Published Papers (10 papers)

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Research

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17 pages, 3360 KiB  
Article
Cell-Free DNA as a Biomarker at Diagnosis and Follow-Up in 256 B and T-Cell Lymphomas
by Ramón Diez-Feijóo, Marcio Andrade-Campos, Joan Gibert, Blanca Sánchez-González, Lierni Fernández-Ibarrondo, Concepción Fernández-Rodríguez, Nieves Garcia-Gisbert, Laura Camacho, Marta Lafuente, Ivonne Vázquez, Luis Colomo, Antonio Salar and Beatriz Bellosillo
Cancers 2024, 16(2), 321; https://doi.org/10.3390/cancers16020321 - 11 Jan 2024
Viewed by 1062
Abstract
Background: Cell-free DNA (cfDNA) analysis has become a promising tool for the diagnosis, prognosis, and monitoring of lymphoma cases. Until now, research in this area has mainly focused on aggressive lymphomas, with scanty information from other lymphoma subtypes. Methods: We selected 256 patients [...] Read more.
Background: Cell-free DNA (cfDNA) analysis has become a promising tool for the diagnosis, prognosis, and monitoring of lymphoma cases. Until now, research in this area has mainly focused on aggressive lymphomas, with scanty information from other lymphoma subtypes. Methods: We selected 256 patients diagnosed with lymphomas, including a large variety of B-cell and T-cell non-Hodgkin and Hodgkin lymphomas, and quantified cfDNA from plasma at the time of diagnosis. We further selected 49 large B-cell lymphomas (LBCL) and analyzed cfDNA levels at diagnosis (pre-therapy) and after therapy. In addition, we performed NGS on cfDNA and tissue in this cohort of LBCL. Results: Lymphoma patients showed a statistically significant higher cfDNA concentration than healthy controls (mean 53.0 ng/mL vs. 5.6 ng/mL, p < 0.001). The cfDNA concentration was correlated with lymphoma subtype, lactate dehydrogenase, the International Prognostic Index (IPI) score, Ann Arbor (AA), and B-symptoms. In 49 LBCL cases, the cfDNA concentration decreased after therapy in cases who achieved complete response (CR) and increased in non-responders. The median cfDNA at diagnosis of patients who achieved CR and later relapsed was higher (81.5 ng/mL) compared with levels of those who did not (38.6 ng/mL). A concordance of 84% was observed between NGS results in tumor and cfDNA samples. Higher VAF in cfDNA is correlated with advanced stage and bulky disease. Conclusions: cfDNA analysis can be easily performed in almost all lymphoma cases. The cfDNA concentration correlated with the characteristics of the aggressiveness of the lymphomas and, in LBCL, with the response achieved after therapy. These results support the utility of cfDNA analysis as a complementary tool in the management of lymphoma patients. Full article
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16 pages, 1190 KiB  
Article
Increased Plasmatic Levels of Exosomes Are Significantly Related to Relapse Rate in Patients with Oral Squamous Cell Carcinoma: A Cohort Study
by Samuel Rodríguez-Zorrilla, Alejandro I. Lorenzo-Pouso, Stefano Fais, Maria A. Logozzi, Davide Mizzoni, Rossella Di Raimo, Alessandro Giuliani, Abel García-García, Alba Pérez-Jardón, Karem L. Ortega, Ángel Martínez-González and Mario Pérez-Sayáns
Cancers 2023, 15(23), 5693; https://doi.org/10.3390/cancers15235693 - 2 Dec 2023
Cited by 1 | Viewed by 1172
Abstract
Background: Oral squamous cell carcinoma (OSCC) is characterized by an immunosuppressive tumor microenvironment. Their plasma-derived exosomes deliver immunomodulatory molecules and cargo that correlate significantly with clinical parameters. This study aims to assess the exosomal profile as a potential tool for early detection of [...] Read more.
Background: Oral squamous cell carcinoma (OSCC) is characterized by an immunosuppressive tumor microenvironment. Their plasma-derived exosomes deliver immunomodulatory molecules and cargo that correlate significantly with clinical parameters. This study aims to assess the exosomal profile as a potential tool for early detection of relapse and long-term outcomes in OSCC patients undergoing conventional therapy. Methods: 27 OSCC patients with a median 38-month follow-up were included in this study. The relationship between NTA-derived parameters and clinical pathological parameters was examined, and receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic efficacy of these values in detecting cancer relapse. Results: Plasmatic levels of exosomes prior to surgery showed a drastic reduction after surgical intervention (8.08E vs. 1.41 × 109 particles/mL, p = 0.006). Postsurgical concentrations of exosomes were higher in patients who experienced relapse compared to those who remained disease-free (2.97 × 109 vs. 1.11 × 109 particles/mL, p = 0.046). Additionally, patients who relapsed exhibited larger exosome sizes after surgery (141.47 vs. 132.31 nm, p = 0.03). Patients with lower concentrations of exosomes prior to surgery demonstrated better disease-free survival compared to those with higher levels (p = 0.012). ROC analysis revealed an area under the curve of 0.82 for presurgical exosome concentration in identifying relapse. Conclusions: Presurgical exosomal plasmatic levels serve as independent predictors of early recurrence and survival in OSCC. All in all, our findings indicate that the detection of peripheral exosomes represents a novel tool for the clinical management of OSCC, with potential implications for prognosis assessment. Full article
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13 pages, 710 KiB  
Article
Liquid Biopsies for Colorectal Cancer and Advanced Adenoma Screening and Surveillance: What to Measure?
by Ellis L. Eikenboom, Saskia M. Wilting, Teoman Deger, Malgorzata I. Srebniak, Monique Van Veghel-Plandsoen, Ruben G. Boers, Joachim B. Boers, Wilfred F. J. van IJcken, Joost H. Gribnau, Peggy Atmodimedjo, Hendrikus J. Dubbink, John W. M. Martens, Manon C. W. Spaander and Anja Wagner
Cancers 2023, 15(18), 4607; https://doi.org/10.3390/cancers15184607 - 17 Sep 2023
Cited by 1 | Viewed by 1106
Abstract
Colorectal cancer (CRC) colonoscopic surveillance is effective but burdensome. Circulating tumor DNA (ctDNA) analysis has emerged as a promising, minimally invasive tool for disease detection and management. Here, we assessed which ctDNA assay might be most suitable for a ctDNA-based CRC screening/surveillance blood [...] Read more.
Colorectal cancer (CRC) colonoscopic surveillance is effective but burdensome. Circulating tumor DNA (ctDNA) analysis has emerged as a promising, minimally invasive tool for disease detection and management. Here, we assessed which ctDNA assay might be most suitable for a ctDNA-based CRC screening/surveillance blood test. In this prospective, proof-of-concept study, patients with colonoscopies for Lynch surveillance or the National Colorectal Cancer screening program were included between 7 July 2019 and 3 June 2022. Blood was drawn, and if advanced neoplasia (adenoma with villous component, high-grade dysplasia, ≥10 mm, or CRC) was detected, it was analyzed for chromosomal copy number variations, single nucleotide variants, and genome-wide methylation (MeD-seq). Outcomes were compared with corresponding patients’ tissues and the MeD-seq results of healthy blood donors. Two Lynch carriers and eight screening program patients were included: five with CRC and five with advanced adenomas. cfDNA showed copy number variations and single nucleotide variants in one patient with CRC and liver metastases. Eight patients analyzed with MeD-seq showed clustering of Lynch-associated and sporadic microsatellite instable lesions separate from microsatellite stable lesions, as did healthy blood donors. In conclusion, whereas copy number changes and single nucleotide variants were only detected in one patient, cfDNA methylation profiles could discriminate all microsatellite instable advanced neoplasia, rendering this tool particularly promising for LS surveillance. Larger studies are warranted to validate these findings. Full article
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19 pages, 875 KiB  
Article
Clinicopathological Profiles Associated with Discordant RAS Mutational Status between Liquid and Tissue Biopsies in a Real-World Cohort of Metastatic Colorectal Cancer
by Elena Brozos-Vázquez, Ramón Manuel Lago-Lestón, Marta Covela, Juan de la Cámara Gómez, Ana Fernández-Montes, Sonia Candamio, Yolanda Vidal, Francisca Vázquez, Alicia Abalo, Rosa López, Cristina Blanco, Laura Muinelo-Romay, Isabel Ferreirós-Vidal and Rafael López-López
Cancers 2023, 15(14), 3578; https://doi.org/10.3390/cancers15143578 - 12 Jul 2023
Viewed by 1122
Abstract
We aimed to identify common mCRC profiles associated with a discordant mutational status of RAS between the standard of care (SoC) tumour tissue tests and ctDNA tests to understand ctDNA detection and improve treatment responses. This was a multicentre, retrospective and prospective study. [...] Read more.
We aimed to identify common mCRC profiles associated with a discordant mutational status of RAS between the standard of care (SoC) tumour tissue tests and ctDNA tests to understand ctDNA detection and improve treatment responses. This was a multicentre, retrospective and prospective study. A total of 366 Spanish mCRC patients were independently recruited. BEAMing ddPCR technology was employed to detect ctDNA RAS mutations, and logistic regression analyses were performed to investigate clinicopathological factors associated with discordance. The highest concordance ratios were observed in profiles with multiple metastatic sites when the liver was present (89.7%; 95% CI 84.8–93.2), profiles with synchronous disease without primary tumour resection (90.2%; 95% CI 83.6–94.3) and profiles with mCRC originating in the left colon (91.3%; 95% CI 85.0–95.0). Metachronous disease originating in the right colon (OR = 6.1; 95% CI 1.7–26.5; p-value = 0.006) or rectum (OR = 5.0; 95% CI 1.5–17.8; p-value = 0.009) showed the highest probability of discrepancies. Primary tumour resection and a higher frequency of single metastases in the peritoneum or lungs in these patients were associated with reduced plasmatic mutation allele fractions (MAFs) and an increased probability of showing false-negative genotypes. Additional testing of patients with mCRC originating in the right colon or rectum with a single non-mutated ctDNA test is advised before the choice of therapy. Full article
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12 pages, 2791 KiB  
Article
Early Diagnosis of Oral Cancer and Lesions in Fanconi Anemia Patients: A Prospective and Longitudinal Study Using Saliva and Plasma
by Ricardo Errazquin, Estela Carrasco, Sonia Del Marro, Anna Suñol, Jorge Peral, Jessica Ortiz, Juan Carlos Rubio, Carmen Segrelles, Marta Dueñas, Alicia Garrido-Aranda, Martina Alvarez, Cristina Belendez, Judith Balmaña and Ramon Garcia-Escudero
Cancers 2023, 15(6), 1871; https://doi.org/10.3390/cancers15061871 - 21 Mar 2023
Cited by 7 | Viewed by 2933
Abstract
Fanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and oral potentially malignant lesions (OPMLs) at early ages. As patients have defects in their DNA repair mechanisms, standard-of-care treatments for OSCC such as radiotherapy and chemotherapy, give rise [...] Read more.
Fanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and oral potentially malignant lesions (OPMLs) at early ages. As patients have defects in their DNA repair mechanisms, standard-of-care treatments for OSCC such as radiotherapy and chemotherapy, give rise to severe toxicities. New methods for early diagnosis are urgently needed to allow for treatment in early disease stages and achieve better clinical outcomes. We conducted a prospective, longitudinal study wherein liquid biopsies from sixteen patients with no clinical diagnoses of OPML and/or OSCC were analyzed for the presence of mutations in cancer genes. The DNA from saliva and plasma were sequentially collected and deep-sequenced, and the clinical evaluation followed over a median time of approximately 2 years. In 9/16 FA patients, we detected mutations in cancer genes (mainly TP53) with minor allele frequencies (MAF) of down to 0.07%. Importantly, all patients that had mutations and clinical follow-up data after mutation detection (n = 6) developed oral precursor lesions or OSCC. The lead-time between mutation detection and tumor diagnosis ranged from 23 to 630 days. Strikingly, FA patients without mutations displayed a significantly lower risk of developing precursor lesions or OSCCs. Therefore, our diagnostic approach could help to stratify FA patients into risk groups, which would allow for closer surveillance for OSCCs or precursor lesions. Full article
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18 pages, 907 KiB  
Article
Plasma-Based microRNA Expression Analysis in Advanced Stage NSCLC Patients Treated with Nivolumab
by Alexia Monastirioti, Chara Papadaki, Despoina Kalapanida, Konstantinos Rounis, Kleita Michaelidou, Maria A. Papadaki, Dimitrios Mavroudis and Sofia Agelaki
Cancers 2022, 14(19), 4739; https://doi.org/10.3390/cancers14194739 - 28 Sep 2022
Cited by 9 | Viewed by 1825
Abstract
Since circulating microRNAs (miRNAs) are involved in the modulation of the immune response, they are tested as liquid biopsy-based biomarkers in patients with NSCLC treated with immunotherapy. We analyzed the expression levels and examined the clinical significance of immunoregulatory miRNAs involved in immune [...] Read more.
Since circulating microRNAs (miRNAs) are involved in the modulation of the immune response, they are tested as liquid biopsy-based biomarkers in patients with NSCLC treated with immunotherapy. We analyzed the expression levels and examined the clinical significance of immunoregulatory miRNAs involved in immune checkpoint regulation (miR-34a, miR-200b, miR-200c), T-cell activity (miR-155), and the function of myeloid-derived suppressive cells (MDSCs) (miR-223) or regulatory T lymphocytes (Tregs) (miR-146a), in patients with advanced NSCLC (N = 69) treated with anti-PD-1 (Nivolumab) immunotherapy as 2nd or 3rd line of treatment therapy. Plasma levels of circulating miRNAs were analyzed by RT-qPCR before the initiation of immunotherapy. Expression of miR-34a, miR-146a, mir-200c, and miR-223 was found to be associated with response to immunotherapy. High miR-200c expression emerged as an independent prognostic factor for inferior overall survival in all patients with NSCLC (OS, HR: 2.243, 95% CI: 1.208–4.163; p = 0.010) and in patients with non-Squamous (non-SqCC) subtype (N = 38) (HR: 2.809, 95% CI: 1.116–7.074; p = 0.028). Low miR-34a expression independently predicted for shorter OS (HR: 3.189, 95% CI: 1.193–8.527; p = 0.021) in the non-SqCC subgroup. Our findings suggest that alterations in circulating miR-200c and miR-34a expression levels are associated with the response and outcome in patients with advanced NSCLC treated with anti-PD1 immunotherapy. Full article
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30 pages, 5082 KiB  
Article
A miRNA-Based Prognostic Model to Trace Thyroid Cancer Recurrence
by Eman A. Toraih, Manal S. Fawzy, Bo Ning, Mourad Zerfaoui, Youssef Errami, Emmanuelle M. Ruiz, Mohammad H. Hussein, Muhib Haidari, Melyssa Bratton, Giovane G. Tortelote, Sylvia Hilliard, Naris Nilubol, Jonathon O. Russell, Mohamed A. Shama, Samir S. El-Dahr, Krzysztof Moroz, Tony Hu and Emad Kandil
Cancers 2022, 14(17), 4128; https://doi.org/10.3390/cancers14174128 - 26 Aug 2022
Cited by 8 | Viewed by 2388
Abstract
Papillary thyroid carcinomas (PTCs) account for most endocrine tumors; however, screening and diagnosing the recurrence of PTC remains a clinical challenge. Using microRNA sequencing (miR-seq) to explore miRNA expression profiles in PTC tissues and adjacent normal tissues, we aimed to determine which miRNAs [...] Read more.
Papillary thyroid carcinomas (PTCs) account for most endocrine tumors; however, screening and diagnosing the recurrence of PTC remains a clinical challenge. Using microRNA sequencing (miR-seq) to explore miRNA expression profiles in PTC tissues and adjacent normal tissues, we aimed to determine which miRNAs may be associated with PTC recurrence and metastasis. Public databases such as TCGA and GEO were utilized for data sourcing and external validation, respectively, and miR-seq results were validated using quantitative real-time PCR (qRT-PCR). We found miR-145 to be significantly downregulated in tumor tissues and blood. Deregulation was significantly related to clinicopathological features of PTC patients including tumor size, lymph node metastasis, TNM stage, and recurrence. In silico data analysis showed that miR-145 can negatively regulate multiple genes in the TC signaling pathway and was associated with cell apoptosis, proliferation, stem cell differentiation, angiogenesis, and metastasis. Taken together, the current study suggests that miR-145 may be a biomarker for PTC recurrence. Further mechanistic studies are required to uncover its cellular roles in this regard. Full article
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21 pages, 3660 KiB  
Article
The Prognostic Value of the Circulating Tumor Cell-Based Four mRNA Scoring System: A New Non-Invasive Setting for the Management of Bladder Cancer
by Consuelo Amantini, Federica Maggi, Jacopo Adolfo Rossi de Vermandois, Marilena Gubbiotti, Antonella Giannantoni, Ettore Mearini, Massimo Nabissi, Daniele Tomassoni, Giorgio Santoni and Maria Beatrice Morelli
Cancers 2022, 14(13), 3118; https://doi.org/10.3390/cancers14133118 - 25 Jun 2022
Cited by 3 | Viewed by 2077
Abstract
Bladder cancer (BC) is one of the most expensive lifetime cancers to treat because of the high recurrence rate, repeated surgeries, and long-term cystoscopy monitoring and treatment. The lack of an accurate classification system predicting the risk of recurrence or progression leads to [...] Read more.
Bladder cancer (BC) is one of the most expensive lifetime cancers to treat because of the high recurrence rate, repeated surgeries, and long-term cystoscopy monitoring and treatment. The lack of an accurate classification system predicting the risk of recurrence or progression leads to the search for new biomarkers and strategies. Our pilot study aimed to identify a prognostic gene signature in circulating tumor cells (CTCs) isolated by ScreenCell devices from muscle invasive and non-muscle invasive BC patients. Through the PubMed database and Cancer Genome Atlas dataset, a panel of 15 genes modulated in BC with respect to normal tissues was selected. Their expression was evaluated in CTCs and thanks to the univariate and multivariate Cox regression analysis, EGFR, TRPM4, TWIST1, and ZEB1 were recognized as prognostic biomarkers. Thereafter, by using the risk score model, we demonstrated that this 4-gene signature significantly grouped patients into high- and low-risk in terms of recurrence free survival (HR = 2.704, 95% CI = 1.010–7.313, Log-rank p < 0.050). Overall, we identified a new prognostic signature that directly impacted the prediction of recurrence, improving the choice of the best treatment for BC patients. Full article
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Review

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28 pages, 5275 KiB  
Review
A Review and In Silico Analysis of Tissue and Exosomal Circular RNAs: Opportunities and Challenges in Thyroid Cancer
by Eman A. Toraih, Mohammad H. Hussein, Manal S. Fawzy and Emad Kandil
Cancers 2022, 14(19), 4728; https://doi.org/10.3390/cancers14194728 - 28 Sep 2022
Viewed by 1876
Abstract
Thyroid cancer (TC) is the most common endocrine tumor. The genetic and epigenetic molecular alterations of TC have become more evident in recent years. However, a deeper understanding of the roles these molecular changes play in TC tumorigenesis and progression is essential in [...] Read more.
Thyroid cancer (TC) is the most common endocrine tumor. The genetic and epigenetic molecular alterations of TC have become more evident in recent years. However, a deeper understanding of the roles these molecular changes play in TC tumorigenesis and progression is essential in developing a successful treatment strategy and improving patients’ prognoses. Circular RNAs (circRNAs), a family of non-coding RNAs, have been implicated in several aspects of carcinogenesis in multiple cancers, including TC. In the current review, we aimed to explore the clinical potential of circRNAs as putative diagnostic, prognostic, and therapeutic targets in TC. The current analyses, including genome-wide circRNA screening and functional enrichment for all deregulated circRNA expression signatures, show that circRNAs display atypical contributions, such as sponging for microRNAs, regulating transcription and translation processes, and decoying for proteins. Given their exceptional clinical advantages, such as higher stability, wider abundance, and occurrence in several body fluids, circRNAs are promising prognostic and theranostic biomarkers for TC. Full article
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22 pages, 2270 KiB  
Review
Emerging Blood-Based Biomarkers for Predicting Immunotherapy Response in NSCLC
by Ana Oitabén, Pablo Fonseca, María J. Villanueva, Carme García-Benito, Aida López-López, Alberto Garrido-Fernández, Clara González-Ojea, Laura Juaneda-Magdalena, Martín E. Lázaro and Mónica Martínez-Fernández
Cancers 2022, 14(11), 2626; https://doi.org/10.3390/cancers14112626 - 26 May 2022
Cited by 8 | Viewed by 4416
Abstract
Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has demonstrated a profitable performance for Non-Small Cell Lung Cancer (NSCLC) cancer treatment in some patients; however, there is still a percentage of patients in whom immunotherapy does not provide the desired results regarding beneficial outcomes. Therefore, [...] Read more.
Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has demonstrated a profitable performance for Non-Small Cell Lung Cancer (NSCLC) cancer treatment in some patients; however, there is still a percentage of patients in whom immunotherapy does not provide the desired results regarding beneficial outcomes. Therefore, obtaining predictive biomarkers for ICI response will improve the treatment management in clinical practice. In this sense, liquid biopsy appears as a promising method to obtain samples in a minimally invasive and non-biased way. In spite of its evident potential, the use of these circulating biomarkers is still very limited in the real clinical practice, mainly due to the huge heterogeneity among the techniques, the lack of consensus, and the limited number of patients included in these previous studies. In this work, we review the pros and cons of the different proposed biomarkers, such as soluble PD-L1, circulating non-coding RNA, circulating immune cells, peripheral blood cytokines, and ctDNA, obtained from liquid biopsy to predict response to ICI treatment at baseline and to monitor changes in tumor and tumor microenvironment during the course of the treatment in NSCLC patients. Full article
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