MCL Literature Feed

A novel Mcl1-degrading AUTAC compound synergizes with proteasome inhibitors by hijacking the adaptive autophagy response, offering a preclinical strategy to overcome proteasome inhibitor resistance in MCL.

Fixed-duration glofitamab monotherapy achieves high complete response rates (78%) in heavily pretreated relapsed/refractory MCL, including post-BTKi patients, offering a potent new off-the-shelf immunotherapy.

A rare case of MCL transdifferentiating into a clonally-related T-cell lymphoma demonstrates a novel transformation mechanism where B-cell markers are lost, complicating diagnosis at relapse.

This review of PROTAC design outlines a novel protein degradation technology with potential to overcome resistance to targeted therapies like BTK inhibitors in mantle cell lymphoma.

The novel agent Ironomycin induces MCL cell death by targeting iron metabolism addiction, identifying a potential new therapeutic strategy based on a metabolic vulnerability.

An MCL patient post-autologous transplant developed persistent COVID-19 with a novel Remdesivir resistance mutation, highlighting the risk of immunocompromised hosts becoming reservoirs for drug-resistant SARS-CoV-2 variants.

Preclinical Galectin-9 induces cell death in MCL cell lines by disrupting autophagy, a novel, apoptosis-independent mechanism to potentially overcome chemoresistance.

This CLL study reveals venetoclax rapidly activates a BAFF-driven survival axis in residual tumor cells, a key resistance mechanism potentially targetable in MCL to deepen BCL2i responses.

This review details Bortezomib's multiple anti-cancer mechanisms and significant toxicities, highlighting the need for next-generation proteasome inhibitors with better therapeutic windows for treating mantle cell lymphoma.

This review synthesizes the evolution of BTK-targeted therapies, from covalent inhibitors to non-covalent agents and degraders, outlining current treatment paradigms and future combination strategies for frontline and relapsed MCL.

This review summarizes the clinical development and efficacy of BTK inhibitors in MCL, detailing common resistance mutations and outlining future directions for this crucial targeted therapy class.

A novel αCD20-EndoP125A antibody fusion protein inhibits MCL growth and dissemination in preclinical models by disrupting tumor-vessel interactions, including angiogenesis, lymphangiogenesis, and vessel co-option.

This meta-analysis quantifies the poor prognosis (median OS ~9 months) for r/r MCL patients post-covalent BTKi treated with standard therapies, highlighting the superior efficacy of brexucabtagene autoleucel.

Preclinically, bortezomib-induced apoptosis depends exclusively on the protein NOXA, which inactivates both MCL-1 and BCL-XL, providing a refined understanding of its mechanism and potential resistance.

In preclinical models, PTEN loss activates the PI3K/AKT pathway, reducing BCR signaling dependence and conferring resistance to ibrutinib, venetoclax, and PI3K inhibitors, identifying a key resistance mechanism.

Longitudinal single-cell analysis of refractory MCL reveals co-evolving tumor heterogeneity and immune evasion, providing a roadmap for overcoming treatment resistance and identifying new therapeutic targets.

This preclinical study identifies a novel CERS6-AS1/FGFR1 axis driving stromal-supported MCL proliferation and stemness, suggesting that co-targeting nucleolin and FGFR1 could overcome microenvironment-mediated resistance.

This review positions pirtobrutinib, a non-covalent BTKi, as a highly effective and safe treatment for relapsed/refractory MCL, especially for patients who have progressed on prior covalent BTK inhibitors.

The KRD regimen (carfilzomib, lenalidomide, dexamethasone) is highly toxic and ineffective for BTKi-relapsed/refractory MCL, with only 13% 12-month OS, establishing this is not a viable salvage therapy.

The non-covalent BTK inhibitor pirtobrutinib shows a 58% overall response rate in relapsed/refractory MCL, providing a crucial new option for patients previously treated with covalent BTK inhibitors.

Bioinformatic analysis of public datasets identified key genes and pathways driving bortezomib resistance in MCL, providing potential biomarkers and therapeutic targets for the relapsed/refractory setting.

This CML review details targeting the ubiquitin-proteasome system to overcome TKI resistance, offering a potential mechanistic strategy for addressing BTKi resistance in MCL.

This preclinical study identifies the CERS6-AS1/FGFR1 axis as a synthetic vulnerability, offering a novel therapeutic strategy to disrupt stromal cell-mediated proliferation and overcome resistance in MCL.

Preclinically, dual inhibition of Hedgehog/GLI1 and Wnt/β-catenin pathways synergistically suppresses MCL cells and enhances sensitivity to chemotherapy and ibrutinib, suggesting a new approach to overcome resistance.

Preclinical data shows the novel CTPS1 inhibitor STP-B has single-agent activity in high-risk MCL (blastoid, TP53-mutated) and synergizes with venetoclax by downregulating MCL1, offering a new combination strategy.

This review explains MCL's clinical heterogeneity through distinct molecular subtypes and genomic alterations like TP53, which serve as key prognostic biomarkers and guide development of novel therapies.

Preclinical data show WEE1 inhibition synergizes with bortezomib by inducing mitotic pyroptosis, a novel cell death mechanism, suggesting a potential strategy to overcome proteasome inhibitor resistance in MCL.

Preclinical data show combining a BCL-XL inhibitor with venetoclax overcomes resistance in MCL models, even in BIM-deficient cells, suggesting a new strategy for venetoclax-refractory patients.

This review highlights BTK's non-catalytic scaffolding function as a novel mechanism of BTKi resistance, presenting a new therapeutic target beyond kinase inhibition for treating B-cell lymphomas like MCL.

BTK inhibition suppresses key metabolic pathways, allowing non-invasive imaging of metabolites like lactate and alanine as early, sensitive biomarkers of therapeutic response in MCL patients.