Chidamide inhibits the NOTCH1-MYC signaling axis in T-cell acute lymphoblastic leukemia

Xi, Meng-Ping; Guo, Shanshan; Bayin, Caicike; Peng, Lijun; Chuffart, Florent; Bourova-Flin, Ekaterina; Rousseaux, Sophie; Khochbin, Saadi; Mi, Jian-Qing; Wang, Jin

doi:10.1007/s11684-021-0877-y

Cited by 11 publications

(11 citation statements)

References 63 publications

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“…The results revealed an ORR of 71%, which was higher than that of chemotherapy alone ( p = 0.037) 6 . Although OS did not significantly differ between groups in this study, chidamide combined with chemotherapy decreased minimal residual disease in T‐ALL patients with a NOTCH1 mutation 44 . Chidamide is rarely tried in B‐ALL due to the widespread application of targeted therapy, immunotherapy, and antibody‐drug conjugates.…”

Section: Chidamide In Acute Lymphoblastic Leukemiacontrasting

confidence: 49%

“…6 Although OS did not significantly differ between groups in this study, chidamide combined with chemotherapy decreased minimal residual disease in T-ALL patients with a NOTCH1 mutation. 44 Chidamide is rarely tried in B-ALL due to the widespread application of targeted therapy, immunotherapy, and antibody-drug conjugates. Clinical trials of chidamide in T-ALL and Ph-like ALL are ongoing.…”

Section: The Treatment Of Acute Lymphoblastic Leukemia With Chidamide...mentioning

confidence: 99%

“…Chidamide participates in the regulation of the apoptosis pathway. Decreases in the expression of the antiapoptotic proteins Bcl‐2, Bcl‐xl and Mcl‐1 were detected after treatment with chidamide, which eventually activated the endogenous apoptotic pathway to induce cell apoptosis 40,44 . Therefore, chidamide may synergistically act with Bcl‐2 or Mcl‐1 inhibitors.…”

Section: Chidamide In Multiple Myelomamentioning

confidence: 99%

“…The oncogenic activity of NOTCH1 in T‐ALL strictly depends on the upregulation of its downstream target MYC 50 . Chidamide was reported to inhibit the NOTCH1‐MYC signaling axis by downregulating the levels of the intracellular form of NOTCH1 and MYC 44 . Specifically, the viability of NOTCH1‐mutated primary T‐ALL cells was reduced after chidamide treatment in a time‐dependent manner.…”

Section: Chidamide In Acute Lymphoblastic Leukemiamentioning

confidence: 99%

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Chidamide: Targeting epigenetic regulation in the treatment of hematological malignancy

Cao

Xue

et al. 2022

Hematological Oncology

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Epigenetic alterations frequently participate in the onset of hematological malignancies. Histone deacetylases (HDACs) are essential for regulating gene transcription and various signaling pathways. Targeting HDACs has become a novel treatment option for hematological malignancies. Chidamide is the first oral selective HDAC inhibitor for HDAC1, HDAC2, HDAC3, and HDAC10 and was first approved for the treatment of R/R peripheral T‐cell lymphoma by the China Food and Drug Administration in 2014. Chidamide was also approved under the name Hiyasta (HBI‐8000) in Japan in 2021. In vitro studies revealed that chidamide could inhibit proliferation and induce apoptosis via cell cycle arrest and the regulation of apoptotic proteins. In clinical studies, chidamide was also efficacious in multiple myeloma, acute leukemia and myelodysplastic syndrome. This review includes reported experimental and clinical data on chidamide monotherapy or chidamide treatment in combination with chemotherapy for various hematological malignancies, offering a rationale for the renewed exploration of this drug.

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Section: Chidamide In Acute Lymphoblastic Leukemiacontrasting

confidence: 49%

Section: The Treatment Of Acute Lymphoblastic Leukemia With Chidamide...mentioning

confidence: 99%

Section: Chidamide In Multiple Myelomamentioning

confidence: 99%

Section: Chidamide In Acute Lymphoblastic Leukemiamentioning

confidence: 99%

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Chidamide: Targeting epigenetic regulation in the treatment of hematological malignancy

Cao

Xue

et al. 2022

Hematological Oncology

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“…As T-ALL is associated with recurrent mutations in functional molecular pathways, work is underway to identify effective targets and therapeutics in many of those pathways. These investigations may lead to additional mechanisms of therapy including targeting NOTCH signaling, the JAK/STAT pathway, the Mapk/RAS pathway, the mTOR pathway and others (NCT03690011, NCT03705507, NCT01523977) [46].…”

Section: Novel Therapy Approaches To Target T-cell Acute Lymphoblasti...mentioning

confidence: 99%

Novel therapies for pediatric acute lymphoblastic leukemia

Graff,

Burke,

Gossai

2023

Current Opinion in Pediatrics

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Purpose of review This review summarizes the current novel therapy landscape in pediatric acute lymphoblastic leukemia (ALL), with a focus on key clinical trials which will shape the future direction of care for these children. Recent findings Recent landmark immunotherapy trials in B-ALL have demonstrated significant benefit for children, adolescents, and young adults with relapsed/refractory high-risk leukemia. Due to these successes, current trials are asking the question as to whether immunotherapy can be successfully incorporated upfront. Additionally, therapies targeting novel antigens or molecular pathways are being developed, providing new options for children previously thought to have incurable leukemia. Summary As survival for ALL has relatively plateaued with maximizing intensity through conventional chemotherapy, continued preclinical and clinical study of novel immunotherapeutic and targeted agents is crucial to further improve outcomes in childhood leukemia.

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Converting “cold” to “hot”: epigenetics strategies to improve immune therapy effect by regulating tumor‐associated immune suppressive cells

Tang,

Cui,

Liu

et al. 2024

Cancer Communications

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Significant developments in cancer treatment have been made since the advent of immune therapies. However, there are still some patients with malignant tumors who do not benefit from immunotherapy. Tumors without immunogenicity are called “cold” tumors which are unresponsive to immunotherapy, and the opposite are “hot” tumors. Immune suppressive cells (ISCs) refer to cells which can inhibit the immune response such as tumor‐associated macrophages (TAMs), myeloid‐derived suppressor cells (MDSCs), regulatory T (Treg) cells and so on. The more ISCs infiltrated, the weaker the immunogenicity of the tumor, showing the characteristics of “cold” tumor. The dysfunction of ISCs in the tumor microenvironment (TME) may play essential roles in insensitive therapeutic reaction. Previous studies have found that epigenetic mechanisms play an important role in the regulation of ISCs. Regulating ISCs may be a new approach to transforming “cold” tumors into “hot” tumors. Here, we focused on the function of ISCs in the TME and discussed how epigenetics is involved in regulating ISCs. In addition, we summarized the mechanisms by which the epigenetic drugs convert immunotherapy‐insensitive tumors into immunotherapy‐sensitive tumors which would be an innovative tendency for future immunotherapy in “cold” tumor.

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Chidamide inhibits the NOTCH1-MYC signaling axis in T-cell acute lymphoblastic leukemia

Cited by 11 publications

References 63 publications

Chidamide: Targeting epigenetic regulation in the treatment of hematological malignancy

Chidamide: Targeting epigenetic regulation in the treatment of hematological malignancy

Novel therapies for pediatric acute lymphoblastic leukemia

Converting “cold” to “hot”: epigenetics strategies to improve immune therapy effect by regulating tumor‐associated immune suppressive cells

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