Targeting mitochondrial respiration for the treatment of acute myeloid leukemia

Carter, Jenna; Hege, Katie; Kalpage, Hasini A.; Edwards, Holly; Hüttemann, Maik; Taub, Jeffrey W.

doi:10.1016/j.bcp.2020.114253

Cited by 32 publications

(16 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, ONC201 was established to target mitochondrial ClpP in AML cells (Ishizawa et al, 2019;Jacques et al, 2020). ONC212, a stronger ClpP activator than ONC201, exhibited enhanced anticancer profiles (Carter et al, 2020;Ferrarini et al, 2021). ADEP analogs, such as ADEP-28 and ADEP-41, also dysregulated mitochondrial ClpP to induce apoptosis in HEK293 T-REx cells (Wong et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Aberrant human ClpP activation disturbs mitochondrial proteome homeostasis to suppress pancreatic ductal adenocarcinoma

Wang

Zhang²,

Wang³

et al. 2022

Cell Chemical Biology

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Aberrant human ClpP activation disturbs mitochondrial proteome homeostasis to suppress pancreatic ductal adenocarcinoma

Wang

Zhang²,

Wang³

et al. 2022

Cell Chemical Biology

View full text Add to dashboard Cite

“…IACS010759 is a small molecule inhibitor that binds a subunit of complex I of the ETC to inhibit electron transfer. IACS010759 efficiency is under evaluation in clinical trials on AML and advanced solid tumors [112,113]. It is to note that in tumors with intact glycolytic system, ETC inhibition may increase glycolysis as an adaptive metabolic response to counteract reduced ATP production and may account for resistance to ETC inhibitors.…”

Section: Targeting Etcmentioning

confidence: 99%

Mitochondrial Metabolism in Carcinogenesis and Cancer Therapy

Moindjie

Rodrigues-Ferreira

Nahmias

2021

Cancers

View full text Add to dashboard Cite

Carcinogenesis is a multi-step process that refers to transformation of a normal cell into a tumoral neoplastic cell. The mechanisms that promote tumor initiation, promotion and progression are varied, complex and remain to be understood. Studies have highlighted the involvement of oncogenic mutations, genomic instability and epigenetic alterations as well as metabolic reprogramming, in different processes of oncogenesis. However, the underlying mechanisms still have to be clarified. Mitochondria are central organelles at the crossroad of various energetic metabolisms. In addition to their pivotal roles in bioenergetic metabolism, they control redox homeostasis, biosynthesis of macromolecules and apoptotic signals, all of which are linked to carcinogenesis. In the present review, we discuss how mitochondria contribute to the initiation of carcinogenesis through gene mutations and production of oncometabolites, and how they promote tumor progression through the control of metabolic reprogramming and mitochondrial dynamics. Finally, we present mitochondrial metabolism as a promising target for the development of novel therapeutic strategies.

show abstract

“…ONC201, the founding member of imipridones, is in clinical trials for multiple advanced cancers, including hematological malignancies and solid tumors including breast cancer and glioblastoma. Recent studies suggest that other than targeting the bulk cancer cells, imipridones also target cancer stem cells and cancer-associated fibroblasts, as well as activate immune cells in the tumor microenvironment [ 177 , 178 ].…”

Section: Therapeutic Development Of Clpxp Ligands As Anti-cancer Agentsmentioning

confidence: 99%

Mitochondrial ATP-Dependent Proteases—Biological Function and Potential Anti-Cancer Targets

Feng

Nouri

Schimmer

2021

Cancers

View full text Add to dashboard Cite

Cells must eliminate excess or damaged proteins to maintain protein homeostasis. To ensure protein homeostasis in the cytoplasm, cells rely on the ubiquitin-proteasome system and autophagy. In the mitochondria, protein homeostasis is regulated by mitochondria proteases, including four core ATP-dependent proteases, m-AAA, i-AAA, LonP, and ClpXP, located in the mitochondrial membrane and matrix. This review will discuss the function of mitochondrial proteases, with a focus on ClpXP as a novel therapeutic target for the treatment of malignancy. ClpXP maintains the integrity of the mitochondrial respiratory chain and regulates metabolism by degrading damaged and misfolded mitochondrial proteins. Inhibiting ClpXP genetically or chemically impairs oxidative phosphorylation and is toxic to malignant cells with high ClpXP expression. Likewise, hyperactivating the protease leads to increased degradation of ClpXP substrates and kills cancer cells. Thus, targeting ClpXP through inhibition or hyperactivation may be novel approaches for patients with malignancy.

show abstract

Targeting mitochondrial respiration for the treatment of acute myeloid leukemia

Cited by 32 publications

References 80 publications

Aberrant human ClpP activation disturbs mitochondrial proteome homeostasis to suppress pancreatic ductal adenocarcinoma

Aberrant human ClpP activation disturbs mitochondrial proteome homeostasis to suppress pancreatic ductal adenocarcinoma

Mitochondrial Metabolism in Carcinogenesis and Cancer Therapy

Mitochondrial ATP-Dependent Proteases—Biological Function and Potential Anti-Cancer Targets

Contact Info

Product

Resources

About