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Article ; Online: Unraveling the Role of the NLRP3 Inflammasome in Lymphoma: Implications in Pathogenesis and Therapeutic Strategies.

Stergiou, Ioanna E / Tsironis, Christos / Papadakos, Stavros P / Tsitsilonis, Ourania E / Dimopoulos, Meletios Athanasios / Theocharis, Stamatios

International journal of molecular sciences

2024 Volume 25, Issue 4

Abstract: Inflammasomes are multimeric protein complexes, sensors of intracellular danger signals, and crucial components of the innate immune system, with the NLRP3 inflammasome being the best characterized among them. The increasing scientific interest in the ... ...

Abstract	Inflammasomes are multimeric protein complexes, sensors of intracellular danger signals, and crucial components of the innate immune system, with the NLRP3 inflammasome being the best characterized among them. The increasing scientific interest in the mechanisms interconnecting inflammation and tumorigenesis has led to the study of the NLRP3 inflammasome in the setting of various neoplasms. Despite a plethora of data regarding solid tumors, NLRP3 inflammasome's implication in the pathogenesis of hematological malignancies only recently gained attention. In this review, we investigate its role in normal lymphopoiesis and lymphomagenesis. Considering that lymphomas comprise a heterogeneous group of hematologic neoplasms, both tumor-promoting and tumor-suppressing properties were attributed to the NLRP3 inflammasome, affecting neoplastic cells and immune cells in the tumor microenvironment. NLRP3 inflammasome-related proteins were associated with disease characteristics, response to treatment, and prognosis. Few studies assess the efficacy of NLRP3 inflammasome therapeutic targeting with encouraging results, though most are still at the preclinical level. Further understanding of the mechanisms regulating NLRP3 inflammasome activation during lymphoma development and progression can contribute to the investigation of novel treatment approaches to cover unmet needs in lymphoma therapeutics.
MeSH term(s)	Humans ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Inflammation/metabolism ; Lymphoma/etiology ; Lymphoma/therapy ; Tumor Microenvironment
Chemical Substances	Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein
Language	English
Publishing date	2024-02-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25042369
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Article: EPH/Ephrin Signaling in Normal Hematopoiesis and Hematologic Malignancies: Deciphering Their Intricate Role and Unraveling Possible New Therapeutic Targets.

Stergiou, Ioanna E / Papadakos, Stavros P / Karyda, Anna / Tsitsilonis, Ourania E / Dimopoulos, Meletios-Athanasios / Theocharis, Stamatios

Cancers

2023 Volume 15, Issue 15

Abstract: Erythropoietin-producing hepatocellular carcinoma receptors (EPHs) represent the largest family of receptor tyrosine kinases (RTKs). EPH interaction with ephrins, their membrane-bound ligands, holds a pivotal role in embryonic development, while, though ... ...

Abstract	Erythropoietin-producing hepatocellular carcinoma receptors (EPHs) represent the largest family of receptor tyrosine kinases (RTKs). EPH interaction with ephrins, their membrane-bound ligands, holds a pivotal role in embryonic development, while, though less active, it is also implicated in various physiological functions during adult life. In normal hematopoiesis, different patterns of EPH/ephrin expression have been correlated with hematopoietic stem cell (HSC) maintenance and lineage-committed hematopoietic progenitor cell (HPC) differentiation, as well as with the functional properties of their mature offspring. Research in the field of hematologic malignancies has unveiled a rather complex involvement of the EPH/ephrinsignaling pathway in the pathophysiology of these neoplasms. Aberrations in genetic, epigenetic, and protein levels have been identified as possible players implicated both in tumor progression and suppression, while correlations have also been highlighted regarding prognosis and response to treatment. Initial efforts to therapeutically target the EPH/ephrin axis have been undertaken in the setting of hematologic neoplasia but are mainly confined to the preclinical level. To this end, deciphering the complexity of this signaling pathway both in normal and malignant hematopoiesis is necessary.
Language	English
Publishing date	2023-08-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15153963
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Article ; Online: Antibody and T-Cell Subsets Analysis Unveils an Immune Profile Heterogeneity Mediating Long-term Responses in Individuals Vaccinated Against SARS-CoV-2.

Agallou, Maria / Koutsoni, Olga S / Michail, Maria / Zisimopoulou, Paraskevi / Tsitsilonis, Ourania E / Karagouni, Evdokia

The Journal of infectious diseases

2022 Volume 227, Issue 3, Page(s) 353–363

Abstract: Background: Based on the fact that coronavirus disease 2019 (COVID-19) is still spreading despite worldwide vaccine administration, there is an imperative need to understand the underlying mechanisms of vaccine-induced interindividual immune response ... ...

Abstract	Background: Based on the fact that coronavirus disease 2019 (COVID-19) is still spreading despite worldwide vaccine administration, there is an imperative need to understand the underlying mechanisms of vaccine-induced interindividual immune response variations. Methods: We compared humoral and cellular immune responses in 127 individuals vaccinated with either BNT162b2, mRNA-1273, or ChAdOx1-nCoV-19 vaccine. Results: Both mRNA vaccines induced faster and stronger humoral responses as assessed by high spike- and RBD-specific antibody titers and neutralizing efficacy in comparison to ChAdOx1-nCoV-19 vaccine. At 7 months postvaccination, a decreasing trend in humoral responses was observed, irrespective of the vaccine administered. Correlation analysis between anti-S1 IgG and interferon- (IFN-) production unveiled a heterogeneous immune profile among BNT162b2-vaccinated individuals. Specifically, vaccination in the high-responder group induced sizable populations of polyfunctional memory CD4 helper T cells (TH1), follicular helper T cells (TFH), and T cells with features of stemness (TSCM), along with high neutralizing antibody production that persisted up to 7 months. In contrast, low responders were characterized by significantly lower antibody titers and memory T cells and a considerably lower capacity for interleukin-2 and IFN- production. Conclusions: We identified that long-term humoral responses correlate with the individuals ability to produce antigen-specific persistent memory T-cell populations.
MeSH term(s)	Humans ; SARS-CoV-2 ; BNT162 Vaccine ; COVID-19/prevention & control ; T-Lymphocyte Subsets ; Antibodies, Neutralizing ; Antibodies, Viral ; Vaccination
Chemical Substances	BNT162 Vaccine ; Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2022-10-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiac421
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Article: The Cytogenetic Profile of Primary and Secondary Plasma Cell Leukemia: Etiopathogenetic Perspectives, Prognostic Impact and Clinical Relevance to Newly Diagnosed Multiple Myeloma with Differential Circulating Clonal Plasma Cells.

Papadhimitriou, Stefanos I / Terpos, Evangelos / Liapis, Konstantinos / Pavlidis, Dimitrios / Marinakis, Theodoros / Kastritis, Efstathios / Dimopoulos, Meletios-Athanasios / Tsitsilonis, Ourania E / Kostopoulos, Ioannis V

Biomedicines

2022 Volume 10, Issue 2

Abstract: Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia that may appear as de-novo leukemia (pPCL) or on the basis of a pre-existing multiple myeloma (MM), called secondary plasma cell leukemia (sPCL). In this prospective study, we have ...

Abstract	Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia that may appear as de-novo leukemia (pPCL) or on the basis of a pre-existing multiple myeloma (MM), called secondary plasma cell leukemia (sPCL). In this prospective study, we have applied a broad panel of FISH probes in 965 newly diagnosed MM (NDMM) and 44 PCL cases of both types to reveal the particular cytogenetic differences among the three plasma cell dyscrasias. In order to evaluate the frequency and patterns of clonal evolution, the same FISH panel was applied both at diagnosis and at the time of first relapse for 81 relapsed MM patients and both at MM diagnosis and during sPCL transformation for the 19 sPCL cases described here. pPCL was characterized by frequent
Language	English
Publishing date	2022-01-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10020209
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Article ; Online: Visualization and analysis of the interaction network of proteins associated with blood-cell targeting autoimmune diseases.

Amanatidou, Athina I / Nastou, Katerina C / Tsitsilonis, Ourania E / Iconomidou, Vassiliki A

Biochimica et biophysica acta. Molecular basis of disease

2020 Volume 1866, Issue 5, Page(s) 165714

Abstract: Blood-cell targeting Autoimmune Diseases (BLADs) are complex diseases that affect blood cell formation or prevent blood cell production. Since these clinical conditions are gathering growing attention, experimental approaches are being used to ... ...

Abstract	Blood-cell targeting Autoimmune Diseases (BLADs) are complex diseases that affect blood cell formation or prevent blood cell production. Since these clinical conditions are gathering growing attention, experimental approaches are being used to investigate the mechanisms behind their pathogenesis and to identify proteins associated with them. However, computational approaches have not been utilized extensively in the study of BLADs. This study aims to investigate the interaction network of proteins associated with BLADs (BLAD interactome) and to identify novel associations with other human proteins. The method followed in this study combines information regarding protein-protein interaction network properties and autoimmune disease terms. Proteins with high network scores and statistically significant autoimmune disease term enrichment were obtained and 14 of them were designated as candidate proteins associated with BLADs. Additionally, clustering analysis of the BLAD interactome was used and allowed the detection of 17 proteins that act as "connectors" of different BLADs. We expect our findings to further extend experimental efforts for the investigation of the pathogenesis and the relationships of BLADs.
MeSH term(s)	Autoantibodies/immunology ; Autoantibodies/metabolism ; Autoantigens/immunology ; Autoantigens/metabolism ; Autoimmune Diseases/blood ; Autoimmune Diseases/immunology ; Biomarkers/analysis ; Biomarkers/blood ; Biomarkers/metabolism ; Blood Cells/immunology ; Blood Cells/metabolism ; Cluster Analysis ; Computational Biology/methods ; Datasets as Topic ; Gene Expression Profiling ; Hematologic Diseases/blood ; Hematologic Diseases/immunology ; Hematopoiesis/immunology ; Humans ; Protein Interaction Mapping/methods ; Protein Interaction Maps/immunology
Chemical Substances	Autoantibodies ; Autoantigens ; Biomarkers
Language	English
Publishing date	2020-02-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	60-7
ISSN	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2020.165714
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Article ; Online: Early microvascular coronary endothelial dysfunction precedes pembrolizumab-induced cardiotoxicity. Preventive role of high dose of atorvastatin.

Efentakis, Panagiotis / Choustoulaki, Angeliki / Kwiatkowski, Grzegorz / Varela, Aimilia / Kostopoulos, Ioannis V / Tsekenis, George / Ntanasis-Stathopoulos, Ioannis / Georgoulis, Anastasios / Vorgias, Constantinos E / Gakiopoulou, Harikleia / Briasoulis, Alexandros / Davos, Constantinos H / Kostomitsopoulos, Nikolaos / Tsitsilonis, Ourania / Dimopoulos, Meletios Athanasios / Terpos, Evangelos / Chłopicki, Stefan / Gavriatopoulou, Maria / Andreadou, Ioanna

Basic research in cardiology

2024

Abstract: Immune checkpoint inhibitors (ICIs) exhibit remarkable antitumor activity and immune-related cardiotoxicity of unknown pathomechanism. The aim of the study was to investigate the ICI class-dependent cardiotoxicity in vitro and pembrolizumab's (Pem's) ... ...

Abstract	Immune checkpoint inhibitors (ICIs) exhibit remarkable antitumor activity and immune-related cardiotoxicity of unknown pathomechanism. The aim of the study was to investigate the ICI class-dependent cardiotoxicity in vitro and pembrolizumab's (Pem's) cardiotoxicity in vivo, seeking for translational prevention means. Cytotoxicity was investigated in primary cardiomyocytes and splenocytes, incubated with ipilimumab, Pem and avelumab. Pem's cross-reactivity was assessed by circular dichroism (CD) on biotechnologically produced human and murine PD-1 and in silico. C57BL6/J male mice received IgG4 or Pem for 2 and 5 weeks. Echocardiography, histology, and molecular analyses were performed. Coronary blood flow velocity mapping and cardiac magnetic resonance imaging were conducted at 2 weeks. Human EA.hy926 endothelial cells were incubated with Pem-conditioned media from human mononuclear cells, in presence and absence of statins and viability and molecular signaling were assessed. Atorvastatin (20 mg/kg, daily) was administered in vivo, as prophylaxis. Only Pem exerted immune-related cytotoxicity in vitro. Pem's cross-reactivity with the murine PD-1 was confirmed by CD and docking. In vivo, Pem initiated coronary endothelial and diastolic dysfunction at 2 weeks and systolic dysfunction at 5 weeks. At 2 weeks, Pem induced ICAM-1 and iNOS expression and intracardiac leukocyte infiltration. At 5 weeks, Pem exacerbated endothelial activation and triggered cardiac inflammation. Pem led to immune-related cytotoxicity in EA.hy926 cells, which was prevented by atorvastatin. Atorvastatin mitigated functional deficits, by inhibiting endothelial dysfunction in vivo. We established for the first time an in vivo model of Pem-induced cardiotoxicity. Coronary endothelial dysfunction precedes Pem-induced cardiotoxicity, whereas atorvastatin emerges as a novel prophylactic therapy.
Language	English
Publishing date	2024-03-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	189755-x
ISSN	1435-1803 ; 0300-8428 ; 0175-9418
ISSN (online)	1435-1803
ISSN	0300-8428 ; 0175-9418
DOI	10.1007/s00395-024-01046-0
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Article ; Online: Belantamab mafodotin, lenalidomide and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma: Part 1 results of a phase I/II study.

Terpos, Evangelos / Gavriatopoulou, Maria / Ntanasis-Stathopoulos, Ioannis / Malandrakis, Panagiotis / Fotiou, Despina / Migkou, Magdalini / Theodorakakou, Foteini / Spiliopoulou, Vasiliki / Kostopoulos, Ioannis V / Syrigou, Rodanthi-Eleni / Eleutherakis-Papaiakovou, Evangelos / Gkolfinopoulos, Stavros / Tsitsilonis, Ourania E / Kastritis, Efstathios / Dimopoulos, Meletios A

Haematologica

2024

Abstract: Preclinical and clinical data demonstrate synergy between belantamab mafodotin (belamaf) and immunomodulatory drugs with limited overlapping toxicities. We investigated the safety and efficacy of belamaf with lenalidomide 25mg on days 1-21 every 28 days ... ...

Abstract	Preclinical and clinical data demonstrate synergy between belantamab mafodotin (belamaf) and immunomodulatory drugs with limited overlapping toxicities. We investigated the safety and efficacy of belamaf with lenalidomide 25mg on days 1-21 every 28 days and dexamethasone 40mg weekly (belamaf-Rd) in transplant ineligible patients with newly diagnosed multiple myeloma. 36 patients (median age 72.5 years) were randomized to receive belamaf at three different doses (2.5/1.9/1.4 mg/kg) every 8 weeks (q8w). Dosing schedule was extended to every 12 weeks (q12w) to account for ocular toxicity. Most common ≥ Grade (Gr) 3 adverse events were fatigue (n=21, 58.3%), rash (n=6, 16.7%), diarrhea (n=8, 22.2%) and COVID-19 (n=5, 13.9%). Gr 3-4 ocular adverse events (OAEs), comprising of visual acuity decline from baseline and/or keratopathy, were reported in 39/216(18.1%)/ 33/244(13.5%)/ 26/207(12.6%) ophthalmological assessments in cohorts 2.5/1.9/1.4 mg/kg. Importantly, Gr 3-4 keratopathy was identified in 9/216 (4.2%)/ 1/244(0.4%)/ 1/207(0.5%) assessments. Most patients (32/36, 88.9%) were treated in the extended q12w schedule, where dose holds due to OAEs were 40, 33 and 16 in cohorts 2.5/1.9/1.4. Overall, ≥VGPR and ≥CR rates were 83.3% and 52.8%, without significant differences among cohorts. Over a median follow-up of 20.3 months no disease progression was reported; 6 patients discontinued treatment due to infection-related death (n=4 COVID-19, n=2 pneumonia) and 1 patient withdrew consent. Based on toxicity/efficacy balance, the recommended phase 2 dose was 1.9 mg/kg q8w, extended to q12w for toxicity. Belamaf-Rd, with the extended schedule for belamaf, has shown important clinical activity and a significant improvement of OAEs with minimal impact on vision-related functioning in an elderly, non-transplant eligible population.
Language	English
Publishing date	2024-02-15
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.284347
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Article: Microtubule Dynamics Deregulation Induces Apoptosis in Human Urothelial Bladder Cancer Cells via a p53-Independent Pathway.

Drosos, Yiannis / Konstantakou, Eumorphia G / Bassogianni, Aggeliki-Stefania / Nikolakopoulos, Konstantinos-Stylianos / Koumoundourou, Dimitra G / Markaki, Sophia P / Tsitsilonis, Ourania E / Voutsinas, Gerassimos E / Valakos, Dimitrios / Anastasiadou, Ema / Thanos, Dimitris / Velentzas, Athanassios D / Stravopodis, Dimitrios J

Cancers

2023 Volume 15, Issue 14

Abstract: Bladder cancer (BLCA) is the sixth most common type of cancer and has a dismal prognosis if diagnosed late. To identify treatment options for BLCA, we systematically evaluated data from the Broad Institute DepMap project. We found that urothelial BLCA ... ...

Abstract	Bladder cancer (BLCA) is the sixth most common type of cancer and has a dismal prognosis if diagnosed late. To identify treatment options for BLCA, we systematically evaluated data from the Broad Institute DepMap project. We found that urothelial BLCA cell lines are among the most sensitive to microtubule assembly inhibition by paclitaxel treatment. Strikingly, we revealed that the top dependencies in BLCA cell lines include genes encoding proteins involved in microtubule assembly. This highlights the importance of microtubule network dynamics as a major vulnerability in human BLCA. In cancers such as ovarian and breast, where paclitaxel is the gold standard of care, resistance to paclitaxel treatment has been linked to p53-inactivating mutations. To study the response of BLCA to microtubule assembly inhibition and its mechanistic link with the mutational status of the p53 protein, we treated a collection of BLCA cell lines with a dose range of paclitaxel and performed a detailed characterization of the response. We discovered that BLCA cell lines are significantly sensitive to low concentrations of paclitaxel, independently of their p53 status. Paclitaxel induced a G2/M cell cycle arrest and growth inhibition, followed by robust activation of apoptosis. Most importantly, we revealed that paclitaxel triggered a robust DNA-damage response and apoptosis program without activating the p53 pathway. Integration of transcriptomics, epigenetic, and dependency data demonstrated that the response of BLCA to paclitaxel is independent of p53 mutational signatures but strongly depends on the expression of DNA repair genes. Our work highlights urothelial BLCA as an exceptional candidate for paclitaxel treatment. It paves the way for the rational use of a combination of paclitaxel and DNA repair inhibitors as an effective, novel therapeutic strategy.
Language	English
Publishing date	2023-07-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15143730
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Article ; Online: Non-Traditional Cardiovascular Risk Factors in Adolescents with Obesity and Metabolic Syndrome May Predict Future Cardiovascular Disease.

Tragomalou, Athanasia / Paltoglou, George / Manou, Maria / Kostopoulos, Ioannis V / Loukopoulou, Sofia / Binou, Maria / Tsitsilonis, Ourania E / Bacopoulou, Flora / Kassari, Penio / Papadopoulou, Marina / Mastorakos, George / Charmandari, Evangelia

Nutrients

2023 Volume 15, Issue 20

Abstract: Obesity in adolescence is associated with significant morbidity and predisposes adolescents to the development of cardiovascular disease (CVD). Although a number of traditional CVD risk factors have been identified in youth, limited data exist regarding ... ...

Abstract	Obesity in adolescence is associated with significant morbidity and predisposes adolescents to the development of cardiovascular disease (CVD). Although a number of traditional CVD risk factors have been identified in youth, limited data exist regarding non-traditional CVD risk factors. In 89 adolescents with metabolic syndrome (MetS), with 60 age-, gender-, and BMI-matched controls, we determined the non-traditional CVD risk factors (hs-CRP, TG/HDL ratio, ApoB/ApoA1 ratio, NAFLD) in order to investigate whether they may be used as biomarkers for predicting future CVD, and we evaluated their response to the implementation of a multidisciplinary, personalized, lifestyle intervention program for 1 year. We demonstrated that the TG/HDL ratio, IL-2, IL-6, IL-17A, and INF-γ were significantly increased in subjects with MetS than in controls, and may be used as biomarkers to predict future CVD. Subjects with MetS had an increased mean carotid intima-media thickness (cIMT) and prevalence of NAFLD than the controls, while the prevalence of NAFLD correlated strongly with cIMT and IL-6 concentrations. Most of the non-traditional cardiovascular risk factors improved following the implementation of a lifestyle intervention program. These findings indicate that adolescents with MetS may have a greater risk for developing atherosclerosis early in life, while early lifestyle intervention is crucial for preventing the arteriosclerotic process in youth.
MeSH term(s)	Adolescent ; Humans ; Metabolic Syndrome/complications ; Metabolic Syndrome/epidemiology ; Pediatric Obesity/complications ; Pediatric Obesity/epidemiology ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/complications ; Non-alcoholic Fatty Liver Disease/epidemiology ; Non-alcoholic Fatty Liver Disease/complications ; Risk Factors ; Carotid Intima-Media Thickness ; Interleukin-6 ; Heart Disease Risk Factors ; Biomarkers
Chemical Substances	Interleukin-6 ; Biomarkers
Language	English
Publishing date	2023-10-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15204342
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Article: Minimal Residual Disease in Multiple Myeloma: Current Landscape and Future Applications With Immunotherapeutic Approaches.

Kostopoulos, Ioannis V / Ntanasis-Stathopoulos, Ioannis / Gavriatopoulou, Maria / Tsitsilonis, Ourania E / Terpos, Evangelos

Frontiers in oncology

2020 Volume 10, Page(s) 860

Abstract: The basic principle that deeper therapeutic responses lead to better clinical outcomes in cancer has emerged technologies capable of detecting rare residual tumor cells. The need for ultra-sensitive approaches for minimal residual disease (MRD) detection ...

Abstract	The basic principle that deeper therapeutic responses lead to better clinical outcomes in cancer has emerged technologies capable of detecting rare residual tumor cells. The need for ultra-sensitive approaches for minimal residual disease (MRD) detection is particularly evident in Multiple Myeloma (MM), where patients will ultimately relapse despite the achievement of complete remission, which is commonplace due to remarkable therapeutic advances. Consequently, current response criteria on MM have been amended based on MRD status and MRD negativity is now considered the most dominant prognostic factor and the most valuable indicator for a subsequent relapse. However, there are particular limitations and several aspects for MRD assessment that remain open. This review summarizes current data on MRD in the clinical management of MM, highlights open issues and discusses the challenges and the endless opportunities arising for both patients and clinicians. Furthermore, it focuses on the current status of MRD in clinical trials, its dynamics in addressing debatable aspects in the clinical handling and its potential role as the prevailing factor for future MRD-driven tailored therapies.
Language	English
Publishing date	2020-05-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2020.00860
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