ArticleBlood advances2018
The SMAC mimetic LCL-161 displays antitumor activity in preclinical models of rituximab-resistant B-cell lymphoma.
Article in Blood advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 29 citations in OpenAlex.
- Final results of a phase 2 clinical trial of LCL161, an oral SMAC mimetic for patients with myelofibrosis.Blood advances · 2021Trial
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- IAPs in cancers: molecular mechanisms, clinical prognostic value, and translational therapeutic potential.Journal of translational medicine · 2026Review
- Mechanisms of first-line treatment resistance in diffuse large B-cell lymphoma.Frontiers in immunology · 2026Review
- The critical role of X-linked inhibitor of apoptosis protein (XIAP) in tumor development.Apoptosis : an international journal on programmed cell death · 2025Review
- Research Progress in the Small Molecule Smac Mimetics in Combination Therapy of Cancer.Current medicinal chemistry · 2025Review
- Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets.MedComm · 2024Review
- Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma.Cancer cell international · 2024Review
- Small-molecule MMRi36 induces apoptosis in p53-mutant lymphomas by targeting MDM2/MDM4/XIAP for degradation.Frontiers in oncology · 2024Article
- Altered pathways and targeted therapy in double hit lymphoma.Journal of hematology & oncology · 2022Review
- Tumour Microenvironment Stress Promotes the Development of Drug Resistance.Antioxidants (Basel, Switzerland) · 2021Review
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Inhibition of BIRC2 Sensitizes α7-HPV-Related Cervical Squamous Cell Carcinoma to Chemotherapy.International journal of molecular sciences · 2021Article
- IAP and HDAC inhibitors interact synergistically in myeloma cells through noncanonical NF-κB- and caspase-8-dependent mechanisms.Blood advances · 2021Article
- Programmed cell death, redox imbalance, and cancer therapeutics.Apoptosis : an international journal on programmed cell death · 2021Review
- Smac mimetics and TRAIL cooperate to induce MLKL-dependent necroptosis in Burkitt's lymphoma cell lines.Neoplasia (New York, N.Y.) · 2021Article
- Current Methods of Post-Translational Modification Analysis and Their Applications in Blood Cancers.Cancers · 2021Review
- BIRC3 and BIRC5: multi-faceted inhibitors in cancer.Cell & bioscience · 2021Review
- Combined the SMAC mimetic and BCL2 inhibitor sensitizes neoadjuvant chemotherapy by targeting necrosome complexes in tyrosine aminoacyl-tRNA synthase-positive breast cancer.Breast cancer research : BCR · 2020Article
- Targeting pathogenic mechanisms in marginal zone lymphoma: from concepts and beyond.Annals of lymphoma · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Clinical observations suggest the existence of shared resistance pathways between rituximab and chemotherapy agents. To explore the mechanisms of rituximab resistance, our group created rituximab-resistant cell lines (RRCLs), which display altered expression of several inhibitor of apoptosis (IAP) family proteins. Here, we provide evidence to support pharmacologically targeting IAPs in lymphoma with LCL-161, a small molecule mimetic of the second mitochondria-derived activator of caspases (SMAC). The antitumor effect of LCL-161 was determined using luminescent adenosine triphosphate assays, flow cytometry, SCID mouse xenografts, and ex vivo patient biopsy sample studies. In vitro exposure to LCL-161 also resulted in a dose-dependent decrease in IAP levels, along with synergistic enhancement of the antitumor effect of cytotoxic chemotherapy, in rituximab-sensitive cell lines and RRCLs. In addition, LCL-161 increased the cytotoxic effect of the proteasome inhibitor carfilzomib in ex vivo lymphoma patient samples. The combination of LCL-161 with the chemotherapy regimen rituximab, gemcitabine, and vinorelbine (RGV) improved in vivo survival compared with RGV alone in severe combined immunodeficient mice implanted with RRCLs but not in animals implanted with rituximab-sensitive cell lines. In summary, LCL-161 exhibits synergistic antitumor activity in both in vitro and in vivo models of resistant lymphoma. Our data support further preclinical investigation of LCL-161 as a novel antilymphoma agent.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.