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Cancers
Special Issues
Treatment Resistance and Predictive Biomarkers in Lymphoid Malignancies
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Treatment Resistance and Predictive Biomarkers in Lymphoid Malignancies

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

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 8014

Special Issue Editor

Dr. Anouk Emadali

E-Mail Website
Guest Editor
1. Translational Epigenetics, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Grenoble-Alpes University, 38000 Grenoble, France
2. Pole Recherche, Grenoble-Alpes University Hospital, 38000 Grenoble, France
Interests: B-cell lymphoma; treatment resistance; epigenetics

Special Issue Information

Dear Colleagues,

Non-Hodgkin lymphomas (NHL) are heterogeneous lymphoid tumors resulting from a complex process of malignant transformation of mature lymphocytes during various stages of differentiation. For most NHL subtypes, advances in chemo-, immuno- and/or targeted therapies have significantly improved patient outcome. However, each entity remains associated with a significant proportion of refractory or relapse cases with a dismal prognosis. In this setting, there is a real clinical need for novel approaches to early identify non-responding patients and uncover cancer cell-intrinsic or extrinsic mechanisms associated with treatment resistance in order to improve refractory/relapse lymphoma patients care.

This Special Issue aims to bring together expert opinions and new clinical, translational or basic research data covering this topic.

We look forward to receiving your contributions.

Dr. Anouk Emadali
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • lymphoma
  • treatment resistance
  • immunotherapy
  • chemotherapy
  • targeted therapy
  • clonal selection
  • cell plasticity
  • minimal residual disease
  • predictive biomarkers

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Published Papers (4 papers)

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Research

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11 pages, 243 KiB  
Article
Obinutuzumab, High-Dose Methylprednisolone (HDMP), and Lenalidomide for the Treatment of Patients with Richter’s Syndrome
by Benjamin M. Heyman, Michael Y. Choi and Thomas J. Kipps
Cancers 2022, 14(24), 6035; https://doi.org/10.3390/cancers14246035 - 8 Dec 2022
Cited by 4 | Viewed by 1516
Abstract
Background: For patients with Richter’s Syndrome (RS), a durable response is rarely achieved with standard therapies. Significant efforts have focused on the development of novel treatments with reduced toxicity. We describe our experience using the novel combination of obinutuzumab, high-dose methylprednisolone (HDMP) and [...] Read more.
Background: For patients with Richter’s Syndrome (RS), a durable response is rarely achieved with standard therapies. Significant efforts have focused on the development of novel treatments with reduced toxicity. We describe our experience using the novel combination of obinutuzumab, high-dose methylprednisolone (HDMP) and lenalidomide (len) in patients with RS. Patients and Methods: Eligible patients included adults with biopsy-proven RS. Patients received obinutuzumab 1000 mg × 8 doses. All patients received HDMP 1000 mg/m2 on days 1–5 of cycles 1–4. Patients were administered len PO daily, starting at a dose of 5 mg. Starting on C2D1, the dose increased every 2 weeks in 5 mg increments to a maximum of 25 mg PO daily. Results: Seven patients were treated. The median dose of len was 10 mg and the median number of cycles of treatment completed was 2. The most common grade 3/4 adverse events were neutropenia (29%) and pulmonary embolism (29%). The overall response rate for the entire cohort was 43% (95% CI, 10–82%). All patients who achieved a response underwent consolidative autologous or allogeneic stem cell transplant and remain in remission to date. Conclusions: The combination of obinutuzumab, HDMP, and len is a well-tolerated, outpatient regimen that could serve as a bridge to transplantation, or as palliation for transplant-ineligible patients with RS. Full article
(This article belongs to the Special Issue Treatment Resistance and Predictive Biomarkers in Lymphoid Malignancies)
13 pages, 1746 KiB  
Article
Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring
by Anne M. R. Schrader, Ruben A. L. de Groen, Rein Willemze, Patty M. Jansen, Koen D. Quint, Arjen H. G. Cleven, Tom van Wezel, Ronald van Eijk, Dina Ruano, J. Hendrik Veelken, Cornelis P. Tensen, Karen J. Neelis, Laurien A. Daniels, Esther Hauben, F. J. Sherida H. Woei-A-Jin, Anne-Marie Busschots, Maarten H. Vermeer and Joost S. P. Vermaat
Cancers 2022, 14(20), 5152; https://doi.org/10.3390/cancers14205152 - 20 Oct 2022
Cited by 3 | Viewed by 1830
Abstract
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only ~55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of primary and relapsed/refractory [...] Read more.
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only ~55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of primary and relapsed/refractory disease has only scarcely been studied in PCDLBCL-LT patients. Therefore, in this retrospective cohort study, 73 primary/pre-treatment and relapsed/refractory biopsies of 57 patients with PCDLBCL-LT were molecularly characterized with triple FISH and targeted next-generation sequencing for 52 B-cell-lymphoma-relevant genes, including paired analysis in 16 patients. In this cohort, 95% of patients harboured at least one of the three main driver alterations (mutations in MYD88/CD79B and/or CDKN2A-loss). In relapsed/refractory PCDLBCL-LT, these oncogenic aberrations were persistently present, demonstrating genetic stability over time. Novel alterations in relapsed disease affected mostly CDKN2A, MYC, and PIM1. Regarding survival, only MYC rearrangements and HIST1H1E mutations were statistically significantly associated with an inferior outcome. The stable presence of one or more of the three main driver alterations (mutated MYD88/CD79B and/or CDKN2A-loss) is promising for targeted therapies addressing these alterations and serves as a rationale for molecular-based disease monitoring, improving response evaluation and early identification and intervention of disease relapses in these poor-prognostic PCDLBCL-LT patients. Full article
(This article belongs to the Special Issue Treatment Resistance and Predictive Biomarkers in Lymphoid Malignancies)
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17 pages, 947 KiB  
Article
P-Glycoprotein Activity at Diagnosis Does Not Predict Therapy Outcome and Survival in Canine B-Cell Lymphoma
by Valéria Dékay, Edina Karai, András Füredi, Kornélia Szebényi, Gergely Szakács and Péter Vajdovich
Cancers 2022, 14(16), 3919; https://doi.org/10.3390/cancers14163919 - 13 Aug 2022
Cited by 1 | Viewed by 1688
Abstract
Various mechanisms are known to be involved in the development of multidrug resistance during cancer treatment. P-glycoprotein (P-gp) decreases the intracellular concentrations of cytotoxic drugs by an energy-dependent efflux mechanism. The aim of this study was to investigate the predictive value of P-gp [...] Read more.
Various mechanisms are known to be involved in the development of multidrug resistance during cancer treatment. P-glycoprotein (P-gp) decreases the intracellular concentrations of cytotoxic drugs by an energy-dependent efflux mechanism. The aim of this study was to investigate the predictive value of P-gp function based on the evaluation of P-gp activity in tumor cells obtained from canine B-cell lymphoma patients at diagnosis. P-gp function of 79 immunophenotyped canine lymphoma samples was determined by flow cytometry using the Calcein assay. Dogs were treated with either the CHOP or the L-CHOP protocol, a subset of relapsed patients received L-asparaginase and lomustine rescue treatments. Among the 79 dogs, the median overall survival time was 417 days, and the median relapse-free period was 301 days. 47 percent of the samples showed high P-gp activity, which was significantly higher in Stage IV cancer patients compared to Stage II + III and V. Whereas staging was associated with major differences in survival times, we found that the intrinsic P-gp activity of tumor cells measured at diagnosis is not predictive for therapy outcome. Further studies are needed to identify the intrinsic and acquired resistant mechanisms that shape therapy response and survival in B-cell canine lymphoma patients. Full article
(This article belongs to the Special Issue Treatment Resistance and Predictive Biomarkers in Lymphoid Malignancies)
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Review

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14 pages, 1122 KiB  
Review
Advances in Understanding of Metabolism of B-Cell Lymphoma: Implications for Therapy
by Katarina Kluckova, Annalisa D’Avola and John Charles Riches
Cancers 2022, 14(22), 5552; https://doi.org/10.3390/cancers14225552 - 11 Nov 2022
Cited by 4 | Viewed by 2469
Abstract
There have been significant recent advances in the understanding of the role of metabolism in normal and malignant B-cell biology. Previous research has focused on the role of MYC and mammalian target of rapamycin (mTOR) and how these interact with B-cell receptor signaling [...] Read more.
There have been significant recent advances in the understanding of the role of metabolism in normal and malignant B-cell biology. Previous research has focused on the role of MYC and mammalian target of rapamycin (mTOR) and how these interact with B-cell receptor signaling and hypoxia to regulate glycolysis, glutaminolysis, oxidative phosphorylation (OXPHOS) and related metabolic pathways in germinal centers. Many of the commonest forms of lymphoma arise from germinal center B-cells, reflecting the physiological attenuation of normal DNA damage checkpoints to facilitate somatic hypermutation of the immunoglobulin genes. As a result, these lymphomas can inherit the metabolic state of their cell-of-origin. There is increasing interest in the potential of targeting metabolic pathways for anti-cancer therapy. Some metabolic inhibitors such as methotrexate have been used to treat lymphoma for decades, with several new agents being recently licensed such as inhibitors of phosphoinositide-3-kinase. Several other inhibitors are in development including those blocking mTOR, glutaminase, OXPHOS and monocarboxylate transporters. In addition, recent work has highlighted the importance of the interaction between diet and cancer, with particular focus on dietary modifications that restrict carbohydrates and specific amino acids. This article will review the current state of this field and discuss future developments. Full article
(This article belongs to the Special Issue Treatment Resistance and Predictive Biomarkers in Lymphoid Malignancies)
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