Immunomodulatory Drugs in Acute Myeloid Leukemia Treatment

Piccolomo, A.; Schifone, Claudia Pia; Strafella, Vanda; Specchia, Giorgina; Musto, Pellegrino; Albano, Francesco

doi:10.3390/cancers12092528

Cited by 14 publications

(9 citation statements)

References 65 publications

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“…Traditionally, new drugs have been tested in newly diagnosed cases of acute myeloid leukemia with relapse or at risk of disadvantage [ 12 , 49 – 51 ]. One possibility is on the MRD setting.…”

Section: Discussionmentioning

confidence: 99%

Targeting AraC-Resistant Acute Myeloid Leukemia by Dual Inhibition of CDK9 and Bcl-2: A Systematic Review and Meta-Analysis

Han

et al. 2022

Journal of Healthcare Engineering

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Purpose. This study aims to determine the influence of targeting araC-resistant acute myeloid leukemia by dual inhibition cyclin-dependent protein kinase (CDK9) and B-cell lymphoma-2 （Bcl-2). Method. The c-Myc inhibitor 10058-F4 and the CDK9 inhibitor AZD4573 were used to determine the cell cycle arrest and apoptosis. Results. 10058-F4 reduces c-Myc protein levels and suppresses HepG2 cell proliferation, possibly by upregulating cyclin-dependent kinase (CDK) inhibitors, p21WAF1, and reducing intracellular alpha-fetal protein (AFP) levels. Conclusion. The combination of AZD4573 and 10058-F4 has a synergistic anti-araC-resistant AML activity, providing a solid database for the aforementioned scientific hypothesis.

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Section: Discussionmentioning

confidence: 99%

Targeting AraC-Resistant Acute Myeloid Leukemia by Dual Inhibition of CDK9 and Bcl-2: A Systematic Review and Meta-Analysis

Han

et al. 2022

Journal of Healthcare Engineering

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“…types of cancers (Murahata and Mitchell, 1976;Pettenati and Ingersoll, 2018). Lastly, immunomodulatory drugs that modify biological responses are also used for cancer therapies (Piccolomo et al, 2020;Wang et al, 2021).…”

Section: Role Of Immunotherapy In Cancer Treatment Thus Farmentioning

confidence: 99%

“…Apart from that, BCG or Bacillus Calmette-Guérin is used broadly for treatment of gut cancer and a few other types of cancers ( Murahata and Mitchell, 1976 ; Pettenati and Ingersoll, 2018 ). Lastly, immunomodulatory drugs that modify biological responses are also used for cancer therapies ( Piccolomo et al, 2020 ; Wang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Electrical Stimulation for Immune Modulation in Cancer Treatments

Das

Langou

et al. 2022

Front. Bioeng. Biotechnol.

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Immunotherapy is becoming a very common treatment for cancer, using approaches like checkpoint inhibition, T cell transfer therapy, monoclonal antibodies and cancer vaccination. However, these approaches involve high doses of immune therapeutics with problematic side effects. A promising approach to reducing the dose of immunotherapeutic agents given to a cancer patient is to combine it with electrical stimulation, which can act in two ways; it can either modulate the immune system to produce the immune cytokines and agents in the patient’s body or it can increase the cellular uptake of these immune agents via electroporation. Electrical stimulation in form of direct current has been shown to reduce tumor sizes in immune-competent mice while having no effect on tumor sizes in immune-deficient mice. Several studies have used nano-pulsed electrical stimulations to activate the immune system and drive it against tumor cells. This approach has been utilized for different types of cancers, like fibrosarcoma, hepatocellular carcinoma, human papillomavirus etc. Another common approach is to combine electrochemotherapy with immune modulation, either by inducing immunogenic cell death or injecting immunostimulants that increase the effectiveness of the treatments. Several therapies utilize electroporation to deliver immunostimulants (like genes encoded with cytokine producing sequences, cancer specific antigens or fragments of anti-tumor toxins) more effectively. Lastly, electrical stimulation of the vagus nerve can trigger production and activation of anti-tumor immune cells and immune reactions. Hence, the use of electrical stimulation to modulate the immune system in different ways can be a promising approach to treat cancer.

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“…Accumulating studies reveal that lenalidomide mediates a plethora of direct and indirect anti-tumor effects [63,74]. Lenalidomide induces cytogenetic remission in more than half of the del(5q) MDS patients [27][28][29].…”

Section: Anti-tumormentioning

confidence: 99%

Novel Molecular Mechanism of Lenalidomide in Myeloid Malignancies Independent of Deletion of Chromosome 5q

Park

Phan

Fang

2021

Cancers

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Lenalidomide as well as other immunomodulatory drugs (IMiDs) have achieved clinical efficacies in certain sub-types of hematologic malignancies, such as multiple myeloma, lower-risk myelodysplastic syndromes (MDS) with a single deletion of chromosome 5q (del(5q)) and others. Despite superior clinical response to lenalidomide in hematologic malignancies, relapse and resistance remains a problem in IMiD-based therapy. The last ten years have witnessed the discovery of novel molecular mechanism of IMiD-based anti-tumor therapy. IMiDs bind human cereblon (CRBN), the substrate receptor of the CRL4 E3 ubiquitin ligase complex. Binding of CRBN with IMiDs leads to degradation of the Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3) and casein kinase 1 alpha. We have found that lenalidomide-mediated degradation of IKZF1 leads to activation of the G protein-coupled receptor 68 (GPR68)/calcium/calpain pro-apoptotic pathway and inhibition of the regulator of calcineurin 1 (RCAN1)/calcineurin pro-survival pathway in MDS and acute myeloid leukemia (AML). Calcineurin inhibitor Cyclosporin-A potentiates the anti-leukemia activity of lenalidomide in MDS/AML with or without del(5q). These findings broaden the therapeutic potential of IMiDs. This review summarizes novel molecular mechanism of lenalidomide in myeloid malignancies, especially without del(5q), in the hope to highlight novel therapeutic targets.

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Immunomodulatory Drugs in Acute Myeloid Leukemia Treatment

Cited by 14 publications

References 65 publications

Targeting AraC-Resistant Acute Myeloid Leukemia by Dual Inhibition of CDK9 and Bcl-2: A Systematic Review and Meta-Analysis

Targeting AraC-Resistant Acute Myeloid Leukemia by Dual Inhibition of CDK9 and Bcl-2: A Systematic Review and Meta-Analysis

Electrical Stimulation for Immune Modulation in Cancer Treatments

Novel Molecular Mechanism of Lenalidomide in Myeloid Malignancies Independent of Deletion of Chromosome 5q

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