Targeting indolent non-Hodgkin lymphoma

Leslie, Lori A.; Skarbnik, Alan P; Bejot, Coleen; Stives, Susan; Feldman, Tatyana; Goy, André

doi:10.1080/17474086.2017.1303374

Cited by 5 publications

(8 citation statements)

References 50 publications

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“…Besides, targeting BCR pathway enzymes like phosphoinositol-3 kinase (PI3K), spleen tyrosine kinase (Syk) and Bruton’s tyrosine kinase (Btk) has been largely successful in treating B-NHL subtypes. Also, inhibition of the microenvironment using immunomodulatory agents and checkpoint inhibitors, and targeting the anti-apoptotic protein of B-cell lymphoma 2 (Bcl-2), can be other attractive therapies ( 14 ) ( Table 1 ).…”

Section: Current Immunotherapeutic Approaches For Nhl’smentioning

confidence: 99%

“…BCL2 is a gene with unknown function that was discovered as the anonymous partner of the heavy chain locus of immunoglobulin in the typical translocation occurred in FL: t ( 14 , 18 , 72 ). In 60-90% of NHL cases, mentioned translocation and the placement of the Bcl-2 gene under the control of the enhancer region of IgH is observed ( 73 , 74 ), whereas upregulation of Bcl-2 in the NHL without this translocation also with increasing relapse of the disease and mortality rate are associated ( 75 ).…”

Section: Current Immunotherapeutic Approaches For Nhl’smentioning

confidence: 99%

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RETRACTED: A Deep Insight Into CAR-T Cell Therapy in Non-Hodgkin Lymphoma: Application, Opportunities, and Future Directions

et al. 2021

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Non-Hodgkin’s lymphoma (NHL) is a cancer that starts in the lymphatic system. In NHL, the important part of the immune system, a type of white blood cells called lymphocytes become cancerous. NHL subtypes include marginal zone lymphoma, small lymphocytic lymphoma, follicular lymphoma (FL), and lymphoplasmacytic lymphoma. The disease can emerge in either aggressive or indolent form. 5-year survival duration after diagnosis is poor among patients with aggressive/relapsing form of NHL. Therefore, it is necessary to understand the molecular mechanisms of pathogenesis involved in NHL establishment and progression. In the next step, we can develop innovative therapies for NHL based on our knowledge in signaling pathways, surface antigens, and tumor milieu of NHL. In the recent few decades, several treatment solutions of NHL mainly based on targeted/directed therapies have been evaluated. These approaches include B-cell receptor (BCR) signaling inhibitors, immunomodulatory agents, monoclonal antibodies (mAbs), epigenetic modulators, Bcl-2 inhibitors, checkpoint inhibitors, and T-cell therapy. In recent years, methods based on T cell immunotherapy have been considered as a novel promising anti-cancer strategy in the treatment of various types of cancers, and particularly in blood cancers. These methods could significantly increase the capacity of the immune system to induce durable anti-cancer responses in patients with chemotherapy-resistant lymphoma. One of the promising therapy methods involved in the triumph of immunotherapy is the chimeric antigen receptor (CAR) T cells with dramatically improved killing activity against tumor cells. The CAR-T cell-based anti-cancer therapy targeting a pan–B-cell marker, CD19 is recently approved by the US Food and Drug Administration (FDA) for the treatment of chemotherapy-resistant B-cell NHL. In this review, we will discuss the structure, molecular mechanisms, results of clinical trials, and the toxicity of CAR-T cell-based therapies. Also, we will criticize the clinical aspects, the treatment considerations, and the challenges and possible drawbacks of the application of CAR-T cells in the treatment of NHL.

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Section: Current Immunotherapeutic Approaches For Nhl’smentioning

confidence: 99%

Section: Current Immunotherapeutic Approaches For Nhl’smentioning

confidence: 99%

RETRACTED: A Deep Insight Into CAR-T Cell Therapy in Non-Hodgkin Lymphoma: Application, Opportunities, and Future Directions

et al. 2021

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“…Various cross-comparisons between the groups were carried out as follows: i) B-NHL (aggressive B-NHL and indolent B-NHL; n=68) vs. non-lymphoma (benign lymphatic disease and healthy control; n=63); ii) B-NHL (n=68) vs. BLD (benign lymphatic disease; n=33); iii) B-NHL (n=68) vs. healthy control (n=30); iv) aggressive B-NHL (n=35) vs. indolent B-NHL (n=33); v) CD20 + B-NHL (n=32) versus CD20 − B-NHL (n=36); vi) early-stage B-NHL (n=49) vs. advanced B-NHL (n=19); ( 7 ) low IPI score (0–2) B-NHL (n=44) vs. high IPI score ( 3 – 5 ) B-NHL (n=24). The comparisons are indicated in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…B-NHL consists of aggressive and indolent subtypes according to its clinical features. Indolent lymphoma accounts for nearly one-third of NHL cases, and it is considered incurable ( 7 ). Indolent lymphoma includes low-grade (grade 1–2) follicular lymphoma (FL), chronic lymphocyte leukemia/small lymphocytic lymphoma, mucosa-associated lymphoid tumors (MALT), minority of mantle cell lymphoma (MCL) and lymphoplasmacytic lymphoma ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Volatile metabonomic profiling in urine to detect novel biomarkers for B‑cell non‑Hodgkin's lymphoma

Hua

Wang

Liu³

et al. 2018

Oncol Lett

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To date, there have been a limited number of useful biomarkers for the screening and monitoring of B-cell non-Hodgkin's lymphoma (B-NHL), which leads to the impetus to discover novel biomarkers for the disease. In the present study, gas chromatography-mass spectrometry (GC-MS) combined with head-space solid-phase micro-extraction (HS-SPME) was employed to analyze the volatile metabolites in the urine samples of 131 subjects. The subjects were divided into 4 main groups: Aggressive B-NHL, indolent B-NHL, benign lymphatic diseases patients and healthy volunteers. The differences of the concentrations of the potential biomarkers among the groups were assessed by non-parametric Wilcoxon's test. The ability of the potential biomarkers to discriminate between the four aforementioned groups was evaluated by receiver operating characteristic curves (ROC). The present study indicated that 4-heptanone, 2-methylpyrazine, 2-methylbutanal, 2,6-dimethyl-7-octen-2-ol and decanoic acid may serve as potential biomarkers for B-NHL. The area under the curve (AUC) values of single potential biomarker ranged from 0.634 to 0.901. The diagnostic models established with combined biomarkers exhibited higher diagnostic values (AUC, 0.824–0.968) compared with the models established with single biomarkers. The present study indicated that urinary volatile metabolites might be potential biomarkers for screening and monitoring of B-NHL.

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“…Treatment for patients with FL or MZL varies widely from "watch and wait", the use of single agent anti-CD20 monoclonal antibodies (mAB), to the use of chemo-immunotherapy. However, novel therapies have recently been FDA-approved for the treatment of these iNHL, 17 including agents that target the (BCR) pathway: Bruton-Tyrosine kinase inhibitors (ibrutinib, zanubrutinib), and the phosphatidylinositol 3-kinases inhibitors (idelalisib, duvelisib, copanlisib, and umbralisib), the subject of our review.…”

Section: Non-hodgkin Lymphomasmentioning

confidence: 99%

PI3k Inhibitors in NHL and CLL: An Unfulfilled Promise

Zeid¹,

Yazbeck²

2023

BLCTT

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Phosphatidylinositol 3-kinases (PI3Ks) are a family of intracellular signal transducer enzymes that can attach a phosphate group to the 3'-hydroxyl of the inositol moiety of membrane-embedded phosphatidylinositol (PI). PI3Ks have been shown to play important roles in cell proliferation, growth, survival, motility, and metabolism. Nonetheless, the PI3K pathway has also shown to be overactivated in several tumors, particularly B-cell malignancies. In recent years, the PI3K signaling pathway has become the major focus of substantial drug discovery and development efforts. Selective (PI3K) inhibitors have been approved for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and indolent non-Hodgkin lymphomas (iNHL), such as follicular lymphoma and marginal-zone lymphoma. Four selective PI3K inhibitors have received accelerated FDA approvals for the treatment of patients with relapsed/refractory (R/R) CLL and/or iNHL based mainly on single-arm Phase II studies: Idelalisib (PI3K-δ inhibitor), copanlisib (dual PI3K-α and PI3K-δ inhibitor), duvelisib (dual PI3K-γ and PI3K-δ inhibitor), and umbralisib (dual PI3Kδ and CK1ε inhibitor). Conversely, recent interim results of randomized control trials (RCTs) involving some of these agents, showed a worrisome trend of decrease in overall survival (OS), and an increase in fatal and severe adverse effects, in comparison with patients in the control arms. Consequently, the class of PI3K inhibitors came under scrutiny, with an FDA expert panel voting on April 21, 2022, recommending that future FDA approvals of PI3K inhibitors be supported by randomized data, rather than single-arm data only, and further discontinuing the use of almost all the PI3K inhibitors in hematologic malignancies. As we believe further research is needed to help potentialize PI3K inhibitors by improving their safety profiles, this mini-review aims at revisiting the clinical successes, the failures, and the promising aspect of this class of drugs, while presenting possible ways that could benefit its successful development.

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Targeting indolent non-Hodgkin lymphoma

Cited by 5 publications

References 50 publications

RETRACTED: A Deep Insight Into CAR-T Cell Therapy in Non-Hodgkin Lymphoma: Application, Opportunities, and Future Directions

RETRACTED: A Deep Insight Into CAR-T Cell Therapy in Non-Hodgkin Lymphoma: Application, Opportunities, and Future Directions

Volatile metabonomic profiling in urine to detect novel biomarkers for B‑cell non‑Hodgkin's lymphoma

PI3k Inhibitors in NHL and CLL: An Unfulfilled Promise

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