Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View
Abstract
:1. Introduction
2. NF-κB and Oncogenesis
3. NF-κB in Multi-Drug Resistant Human Tumor
4. NF-κB as Molecular Drug Target
4.1. Natural Compounds
4.1.1. Curcumin
4.1.2. Essential Oils
4.1.3. Triterpene Acids
4.2. Synthetic Compounds
4.2.1. Dehydroxymethylepoxyquinomicin (DHMEQ): A Selective Inhibitor of NF-κB
4.2.2. Proteasome Inhibitor
4.2.3. Epigenetic Agents
4.2.4. Silencing of MDA-9/Syntenin
5. Other Scientific Evidence
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Identifier Number | Official Title | Date | Conclusions |
---|---|---|---|
NCT00512798 | (Inhibition of NF-κB Signaling in Melanoma Therapy) A Phase I/II Clinical Trial of PS-341, a Proteasome Inhibitor, in Combination with an Extended Continuous Oral Schedule of Temozolomide in Patients with Advanced Refractory Solid Tumors with the Phase II Component Only in Patients with Melanoma | 2003–2008 | Terminated Due to Lack of Efficacy |
NCT03047837 | A Randomized, Phase II, Double-Blind, Placebo-controlled, Multicenter, 2x2 Factorial Design Biomarker Tertiary Prevention Trial of Low-dose Aspirin and Metformin in Stage I–III Colorectal Cancer Patients. | 2017–2020 | Not Terminated |
NCT01681368 | Phase II Open Label Non-Randomized Single Agent Study of the SMAC (Second Mitochondrial-Derived Activator of Caspases)-Mimetic Birinapant (TL32711; NSC 756502) in Relapsed Platinum Resistant or Refractory Epithelial Ovarian Cancer; Primary Peritoneal | 2012–2014 | Terminated Due to Lack of a Clinical Benefit |
NCT04208334 | A Double-blind, Placebo-Controlled Randomized Trial Phase II Evaluating the Effect of Curcumin for Treatment of Cancer Anorexia–Cachexia Syndrome in Patients with Stage III–IV of Head and Neck Cancer | 2020–2020 | Not Terminated |
NCT04234022 | Zn-DDC to Target Hypoxia-NF-ĸB–CSCs Pathway and Improve the Treatment Outcomes of Hematological Malignancies—A Translation Bench Study | 2020–2023 | Not Terminated (Not Yet Recruiting) |
NCT01740323 | Meriva for Treatment-Induced Inflammation and Fatigue in Women with Breast Cancer | 2015–2018 | Completed (the Study Only Highlighted a Slight Advantage by Curcumin Treatment, Compared to Placebo, to Reduce Symptoms of Fatigue Associated with Excessive NF-ĸB Activity in BRCA Patients) |
NCT00899353 | Inhibition of NF-ĸB for Prevention of Disease Progression in Indolent B Cell Malignancies | 2008–2012 | Terminated (Original Principal Investigator Left the Institution.) |
NCT02765854 | Phase II Trial of Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone, and Lenalidomide, Randomized with NF-kB2 Rearrangement (Proteasome Inhibitor NF-kB2 Rearrangement Driven Trial: PINR) | 2016–2021 | Not Terminated |
NCT01132911 | A Phase I Study of Vorinostat and Bortezomib in Children with Refractory of Recurrent Solid Tumors, Including CNS Tumors and Lymphomas | 2010–2011 | Completed (No Study Results Posted on ClinicalTrials.gov) |
NCT02144675 | A Randomized Phase II Study of NF-κB Inhibition During Induction Chemotherapy for Patients with Acute Myelogenous Leukemia | 2009–2016 | Completed (It Was Not Reported if the Treatment with Choline Magnesium Trisalicylate and Chemotherapy Produced a Modulation of NF-ĸB Transcriptional Targets and/or Drug Efflux in at Least 50% of Patients) |
NCT03978624 | Window of Opportunity Platform Study to Define Immunogenomic Changes with Pembrolizumab Alone and in Rational Combinations in Muscle-Invasive Bladder Cancer | 2019–2021 | Not Terminated |
NCT00280761 | A Biologic Study of Global Gene Expression, NF-Kappa B and p53 in Adenocarcinoma of the Rectum | 2003–2021 | Not Terminated |
NCT00541359 | A Phase I Trial of PS-341 in Combination with Topotecan in Advanced Solid Tumor Malignancies | 2004–2011 | Completed (No Study Results Posted on ClinicalTrials.gov) |
NCT00305734 | Phase II Trial of PS-341 (Bortezomib, NSC-681239) Followed by the Addition of Gemcitabine at Progression in Recurrent or Metastatic Nasopharyngeal Carcinoma | 2006–2007 | Completed (No Study Results Posted on ClinicalTrials.gov) |
NCT00745134 | A Randomized Double Blinded Study of Curcumin with Pre-Operative Capecitabine and Radiation Therapy Followed by Surgery for Rectal Cancer | 2008–2021 | Not Terminated |
NCT03382340 | A Phase 1/2a Open-Label, Dose-Escalation/Dose-Expansion Safety, Tolerability and Pharmacokinetic Study of IMX-110 (a Nanoparticle Encapsulating a Stat3/NF-kB/Poly-Tyrosine Kinase Inhibitor and Low-Dose Doxorubicin) in Patients with Advanced Solid Tumors | 2018–2021 | Not terminated |
NCT00113841 | Pilot Study of Curcumin (Diferuloylmethane Derivative) with or without Bioperine in Patients with Multiple Myeloma | 2004–2009 | Completed (Curcumin and bioperine compared to Curcumin Alone Produced a Higher Reduction of NF-ĸB and Its Related Gene Expression in the Multiple Myeloma cells). |
NCT00305747 | Phase I Study of BioResponse-Dim in Non-Metastatic, Hormone-Refractory Prostate Cancer Patients with Rising Serum PSA | 2005–2010 | Completed (No Study Results Posted on ClinicalTrials.gov) |
NCT01269203 | A Phase II Randomized Study of the Efficacy of Curcumin for Reducing Symptoms During Maintenance Therapy in Multiple Myeloma Patients | 2012–2015 | Withdrawn |
NCT00156299 | A Pilot Study of NF-kB Inhibition During Induction Chemotherapy for Patients with Acute Myelogenous Leukemia (AML) | 2003–2008 | Terminated (Replaced by Another Study) |
NCT02944578 | Biomolecular Effects of Topical Curcumin in HSIL Cervical Neoplasia | 2017–2021 | Not Terminated |
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Labbozzetta, M.; Notarbartolo, M.; Poma, P. Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View. Int. J. Mol. Sci. 2020, 21, 3070. https://doi.org/10.3390/ijms21093070
Labbozzetta M, Notarbartolo M, Poma P. Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View. International Journal of Molecular Sciences. 2020; 21(9):3070. https://doi.org/10.3390/ijms21093070
Chicago/Turabian StyleLabbozzetta, Manuela, Monica Notarbartolo, and Paola Poma. 2020. "Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View" International Journal of Molecular Sciences 21, no. 9: 3070. https://doi.org/10.3390/ijms21093070