Effects of azacitidine: A Synthesis of Findings from 25 Studies

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Original Abstract of the Article

Major Research Findings

Azacitidine has shown promising results in treating various types of cancer. 24 demonstrates its effectiveness in treating juvenile myelomonocytic leukemia (JMML) by targeting MCL-1 and BCL-XL, key proteins required for the survival of JMML cells. In this study, azacitidine was combined with BH3 mimetic drugs, resulting in synergistic effects in eliminating JMML cells. This highlights the potential of azacitidine in combination therapies for treating JMML, especially for cases resistant to standard treatments.

Azacitidine also shows therapeutic potential in treating myelodysplastic syndromes (MDS). 1 reports a phase I trial evaluating the combination of azacitidine with plerixafor and G-CSF, showing encouraging response rates in MDS patients. This regimen demonstrates the potential for improving treatment outcomes by enhancing the sensitivity of MDS cells to azacitidine.

Further research highlights the effectiveness of azacitidine as a maintenance therapy for MDS. 7 emphasizes the value of continuous azacitidine treatment, suggesting that it has a cumulative effect on MDS cells and contributes to prolonged survival. Notably, this study suggests that prolonged survival is not necessarily dependent on achieving complete remission.

Benefits and Risks

Benefit Summary

Azacitidine shows promise in treating various cancers, particularly in combination with other drugs. It has shown effectiveness in treating JMML ( 24 ), MDS ( 1 , 7 ), and AML ( 15 , 8 ). Additionally, azacitidine has been shown to mitigate graft-versus-host disease (GvHD) ( 12 ).

Risk Summary

The most common side effects associated with azacitidine include anemia, neutropenia, thrombocytopenia, gastrointestinal issues, and skin problems. 11 It is important to note that azacitidine should not be used during pregnancy or while breastfeeding.

Comparison of Studies

Commonalities Among Studies

The majority of studies indicate that azacitidine inhibits DNA methylation, effectively suppressing cancer cell growth. It also shows potential benefits in combination therapies, improving treatment outcomes.

Differences Among Studies

While azacitidine demonstrates effectiveness across various cancer types, the specific cancers targeted and the optimal combinations with other drugs vary across studies.

Consistency and Discrepancies of Results

Although azacitidine shows promising results in treating different cancers, the specific effects and the optimal treatment combinations vary depending on the cancer type and other drug combinations. Despite this, the majority of research supports the effectiveness of azacitidine in suppressing cancer cell growth by inhibiting DNA methylation. Further studies are necessary to understand its long-term safety and efficacy, and to optimize treatment strategies for different cancers.

Practical Applications and Cautions

While azacitidine holds potential for treating various cancers, it's crucial to remember that it has side effects. It is essential to consult a doctor before considering azacitidine treatment.

Limitations of Current Research

Current research on azacitidine has limitations. Its long-term safety and efficacy need further investigation. Also, the optimal treatment combinations with other drugs, as well as the effectiveness for specific cancer types, requires further study. Additionally, azacitidine should not be used during pregnancy or breastfeeding.

Future Research Directions

Further research on azacitidine is crucial to optimize treatment strategies for various cancers. This includes investigating its long-term safety and efficacy, exploring its effectiveness in combination with other drugs, and understanding its mechanism of action for specific cancer types.

Conclusion

Azacitidine shows significant promise in treating various cancers, particularly in combination with other drugs. It effectively inhibits DNA methylation, slowing cancer cell growth. While azacitidine offers hope for cancer treatment, further research is essential to fully understand its potential and safety. It is vital to consult with a medical professional for personalized treatment decisions.

Literature analysis of 25 papers
Positive Content
23
Neutral Content
2
Negative Content
0
Article Type
1
0
0
2
25
1.

A phase I trial evaluating the effects of plerixafor, G-CSF, and azacitidine for the treatment of myelodysplastic syndromes.

Author: HuseltonEric, RettigMichael P, FletcherTheresa, RitcheyJulie, GehrsLeah, McFarlandKyle, ChristStephanie, EadesWilliam C, TrinkausKathryn, RomeeRizwan, KulkarniShashikant, GhobadiArmin, AbboudCamille, CashenAmanda F, Stockerl-GoldsteinKeith, UyGeoffrey L, VijRavi, WesterveltPeter, DiPersioJohn F, SchroederMark A

MDS treatment

This study investigates the potential of combining G-CSF and plerixafor with azacitidine in patients with myelodysplastic syndromes (MDS). Results suggest that this regimen is tolerable and has encouraging response rates, with higher response rates observed in patients with blast mobilization.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease.

Author: TobiassonMagnus, AbdulkadirHani, LennartssonAndreas, KatayamaShintaro, MarabitaFrancesco, De PaepeAyla, KarimiMohsen, KrjutskovKaarel, EinarsdottirElisabet, GrövdalMichael, JanssonMonika, Ben AzenkoudAsmaa, CorddeduLina, LehmannSören, EkwallKarl, KereJuha, Hellström-LindbergEva, UngerstedtJohanna

Gene expression
MDS treatment

This study globally evaluated the epigenetic effects of azacitidine (Aza) on myelodysplastic syndromes (MDS) bone marrow progenitor cells. Aza induced a general increase in gene expression and moderate DNA hypomethylation, suggesting that its effects may be mediated by both epigenetic and non-epigenetic mechanisms.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

4.

Effects of azacitidine on matrix metalloproteinase-9 in acute myeloid leukemia and myelodysplasia.

Author: BernalTeresa, Moncada-PazosAngela, Soria-VallesClara, Gutiérrez-FernándezAna

Myelodysplastic syndromes treatment
Disease progression

Azacitidine, a drug used to treat myelodysplastic diseases, can increase MMP9 expression, a protein involved in the invasiveness of leukemia cells, in vitro. This finding may partially explain the clinical failure of the drug and the progression to a more aggressive disease.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Effects of azacitidine compared with conventional care regimens in elderly (≥ 75 years) patients with higher-risk myelodysplastic syndromes.

Author: SeymourJohn F, FenauxPierre, SilvermanLewis R, MuftiGhulam J, Hellström-LindbergEva, SantiniValeria, ListAlan F, GoreSteven D, BackstromJay, McKenzieDavid, BeachC L

Improved survival
Well tolerated
Anemia
Neutropenia
Thrombocytopenia

This study compared the effectiveness of azacitidine (AZA) to conventional care regimens (CCR) in patients with higher-risk myelodysplastic syndromes (MDS). AZA significantly improved overall survival and was well tolerated compared to CCR.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

The effects of the DNA methyltranfserases inhibitor 5-Azacitidine on ageing, oxidative stress and DNA methylation of adipose derived stem cells.

Author: KornickaKatarzyna, MaryczKrzysztof, MarędziakMonika, TomaszewskiKrzysztof A, NicpońJakub

MSC rejuvenation

This study investigated the effect of the DNA methyltransferase (DNMT) inhibitor 5-Azacytidine (5-AZA) on the aged phenotype of mesenchymal stem cells (MSCs). The study found that 5-AZA reversed the aged phenotype of MSCs, increasing proliferation rate and reducing oxidative stress factors and DNA methylation status.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Synergistic effects of PRIMA-1<sup>Met</sup> (APR-246) and 5-azacitidine in <i>TP53</i>-mutated myelodysplastic syndromes and acute myeloid leukemia.

Author: MaslahNabih, SalomaoNorman, DrevonLouis, VergerEmmanuelle, PartoucheNicolas, LyPierre, AubinPhilippe, NaouiNadia, SchlageterMarie-Helene, BallyCecile, MiekoutimaElsa, RahméRamy, Lehmann-CheJacqueline, AdesLionel, FenauxPierre, CassinatBruno, GiraudierStephane

Treat myeloid leukemia

This study investigated the efficacy of PRIMA-1<sup>Met</sup> (APR-246, APR) in combination with 5-azacitidine (AZA) for the treatment of myelodysplastic syndromes and acute myeloid leukemia with *TP53* mutations. Low doses of APR on its own or in combination with AZA showed significant efficacy both in vitro and in vivo.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Effects of azacitidine in 93 patients with <i>IDH1/2</i> mutated acute myeloid leukemia/myelodysplastic syndromes: a French retrospective multicenter study.

Author: WillekensC, RahmeR, DuchmannM, VidalV, SaadaV, BroutinS, DelahousseJ, RennevilleA, MarceauA, ClappierE, UzunovM, RossignolJ, PascalL, SimonL, MicolJ B, PasquierF, RaffouxE, PreudhommeC, QuivoronC, ItzyksonR, Penard-LacroniqueV, PaciA, FenauxP, AttarE C, FrattiniM, BraunT, AdesL, De BottonS

MNs treatment

This study investigated the clinical impact of azacitidine (AZA) in myeloid neoplasms (MNs) with IDH1/2 mutations and the potential of serum 2HG as a marker of response to AZA. While AZA showed some response rate, it was not consistently effective, and serum 2HG levels did not reliably predict response.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.

Language : English

11.

Azacitidine adverse effects in patients with myelodysplastic syndromes.

Author: San Miguel AmigoL, Franco OsorioR, Mercadal VilchezS, Martínez-FrancésA

Treat myelodysplastic syndromes
GI toxicity
Hematologic toxicity
Skin toxicity

This article discusses the management of side effects associated with azacitidine treatment for high-risk myelodysplastic syndromes. Hematological toxicity is managed with growth factor support and blood transfusions, while nonhematological side effects are primarily gastrointestinal and cutaneous.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

12.

Azacitidine Mitigates Graft-versus-Host Disease via Differential Effects on the Proliferation of T Effectors and Natural Regulatory T Cells In Vivo.

Author: CooperMatthew L, ChoiJaebok, KarpovaDarja, VijKiran, RitcheyJulie, SchroederMark A, DiPersioJohn F

GvHD mitigation

Azacitidine (AzaC) requires the presence of natural regulatory T cells (nTregs) in the donor graft to optimally protect against graft-versus-host disease (GvHD) in mice.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Azacitidine improves antitumor effects of docetaxel and cisplatin in aggressive prostate cancer models.

Author: FestucciaClaudio, GravinaGiovanni Luca, D'AlessandroAnna Maria, MuziPaola, MillimaggiDanilo, DoloVincenza, RicevutoEnrico, VicentiniCarlo, BolognaMauro

Chemosensitizing agent
Tumor growth delay

Azacitidine may enhance the effectiveness of docetaxel and cisplatin in treating hormone-refractory prostate cancer.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

14.

Azacitidine in CMML: matched-pair analyses of daily-life patients reveal modest effects on clinical course and survival.

Author: PleyerLisa, GermingUlrich, SperrWolfgang R, LinkeschWerner, BurgstallerSonja, StauderReinhard, GirschikofskyMichael, SchrederMartin, PfeilstockerMichael, LangAlois, SliwaThamer, GeisslerDietmar, SchlickKonstantin, Placher-SorkoGudrun, TheilerGeorg, ThalerJosef, MitrovicMartina, NeureiterDaniel, ValentPeter, GreilRichard

CMML treatment
Complete response
Survival
Cytogenetics
Monocyte count

Azacitidine is a promising treatment option for chronic myelomonocytic leukemia (CMML). This study of 48 CMML patients showed high overall response rates to azacitidine, with a trend toward longer survival compared to best supportive care and hydroxyurea. Azacitidine appears to be a safe and effective treatment for both myelodysplastic and myeloproliferative CMML.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Adverse effects of azacitidine: onset, duration, and treatment.

Author: Martínez-FrancésAntonio

Treat myelodysplastic syndromes
Hematologic toxicity
Non-hematologic toxicity

This article discusses the use of azacitidine, a DNA methyltransferase inhibitor, in treating high-risk myelodysplastic syndromes. Azacitidine has improved survival in these patients, but requires careful management of side effects, primarily hematological and nonhematological.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

18.

Romidepsin and Azacitidine Synergize in their Epigenetic Modulatory Effects to Induce Apoptosis in CTCL.

Author: RozatiSima, ChengPhil F, WidmerDaniel S, FujiiKazuyasu, LevesqueMitchell P, DummerReinhard

Antiproliferative

Cutaneous T-cell lymphomas (CTCL) are often refractory to current therapies. This study explores the synergistic antiproliferative effects of romidepsin, an HDAC inhibitor, and azacitidine, a demethylating agent, in CTCL.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

22.

Combinatorial effects of azacitidine and trametinib on NRAS-mutated melanoma.

Author: HanftKlara-Maria, HamedEbrahem, KaiserMax, WürtembergerJulia, SchneiderMichaela, PietschTorsten, FeigeUrsula, MeissFrank, KrengelSven, NiemeyerCharlotte, HettmerSimone

Improved melanoma response
None mentioned

This study reports on a child with a rare cancer called congenital melanocytic nevus (CMN) syndrome. The child was successfully treated with a combination of azacitidine and trametinib. This combination therapy was more effective than trametinib alone and might be a promising treatment for other RAS-driven cancers.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

23.

Chronic azacitidine treatment results in differentiating effects, sensitizes against bicalutamide in androgen-independent prostate cancer cells.

Author: GravinaGiovanni Luca, FestucciaClaudio, MillimaggiDanilo, DoloVincenza, TomboliniVincenzo, de VitoMariano, VicentiniCarlo, BolognaMauro

AR expression
PSA expression
cell survival
proliferation

Demethylating agents, such as Aza-CR, can reactivate androgen receptor (AR) expression in androgen-independent prostate cancer cells. This suggests that epigenetic reactivation of AR may be a potential therapeutic target for bicalutamide therapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

25.

CDK7 inhibition induces apoptosis in acute myeloid leukemia cells and exerts synergistic antileukemic effects with azacitidine <i>in&#160;vitro</i> and <i>in&#160;vivo</i>.

Author: ZhangShuai, FengRu, BaiJiefei, NingShangyong, XuXiaodong, SunJie, WuMeng, LiuHui

AML cell apoptosis
Synergistic antileukemia effect

This study investigated the effects of THZ1, a CDK7 inhibitor, on acute myeloid leukemia (AML) cells. THZ1 induced apoptosis and cell cycle arrest in AML cells. Combined with azacitidine (AZA), THZ1 exhibited synergistic antileukemic effects, suggesting its potential as a therapeutic strategy for AML.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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