Recent advances of IDH1 mutant inhibitor in cancer therapy

Tian, Wangqi; Zhang, Weitong; Wang, Yifan; Jin, Ruyi; Wang, Yuwei; Guo, Hui; Tang, Yuping; Yao, Xiaojun

doi:10.3389/fphar.2022.982424

Cited by 34 publications

(15 citation statements)

References 104 publications

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“…To date, numerous mIDH-selective inhibitors have been developed, and some of them have been shown to effectively reduce 2-HG production in preclinical tumor models and/or in patients [ 4 , 46 , 47 ]. As will be described in more detail in Section 7 , almost all of them effectively inhibit the predominant IDH1 R132H mutation and many classes also target additional mutations, which could be advantageous for imaging in glioma patients with non-canonical mutations.…”

Section: Considerations For the Development Of Midh-selective Pet-tra...mentioning

confidence: 99%

Mutated Isocitrate Dehydrogenase (mIDH) as Target for PET Imaging in Gliomas

2023

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Gliomas are the most common primary brain tumors in adults. A diffuse infiltrative growth pattern and high resistance to therapy make them largely incurable, but there are significant differences in the prognosis of patients with different subtypes of glioma. Mutations in isocitrate dehydrogenase (IDH) have been recognized as an important biomarker for glioma classification and a potential therapeutic target. However, current clinical methods for detecting mutated IDH (mIDH) require invasive tissue sampling and cannot be used for follow-up examinations or longitudinal studies. PET imaging could be a promising approach for non-invasive assessment of the IDH status in gliomas, owing to the availability of various mIDH-selective inhibitors as potential leads for the development of PET tracers. In the present review, we summarize the rationale for the development of mIDH-selective PET probes, describe their potential applications beyond the assessment of the IDH status and highlight potential challenges that may complicate tracer development. In addition, we compile the major chemical classes of mIDH-selective inhibitors that have been described to date and briefly consider possible strategies for radiolabeling of the most promising candidates. Where available, we also summarize previous studies with radiolabeled analogs of mIDH inhibitors and assess their suitability for PET imaging in gliomas.

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Section: Considerations For the Development Of Midh-selective Pet-tra...mentioning

confidence: 99%

Mutated Isocitrate Dehydrogenase (mIDH) as Target for PET Imaging in Gliomas

2023

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“…While this agent improves clinical outcomes, patients ultimately relapse. 16 Wu developed the first genetically engineered mouse model for mIDH1 ICC to understand the impacts of mIDH1 inhibition and identify strategies to improve its efficacy. He showed that the predominant IDH1 mutant allele in cholangiocarcinoma produces higher levels of R-2HG than the allele commonly found in glioblastoma.…”

Section: Importance Of T Cells In Targeting Midh1 In Cholangiocarcinomamentioning

confidence: 99%

“…The mIDH1 inhibitor ivosidenib was approved for mIDH1 advanced or metastatic cholangiocarcinoma in 2021. While this agent improves clinical outcomes, patients ultimately relapse 16 . Wu developed the first genetically engineered mouse model for mIDH1 ICC to understand the impacts of mIDH1 inhibition and identify strategies to improve its efficacy.…”

Section: Metabolic Regulation Of the Anticancer Immune Responsementioning

confidence: 99%

Immunometabolism at the crossroads of obesity and cancer—a Keystone Symposia report

Cable¹,

Rathmell

Pearce

et al. 2023

Annals of the New York Academy of Sciences

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Immunometabolism considers the relationship between metabolism and immunity. Typically, researchers focus on either the metabolic pathways within immune cells that affect their function or the impact of immune cells on systemic metabolism. A more holistic approach that considers both these viewpoints is needed. On September 5–8, 2022, experts in the field of immunometabolism met for the Keystone symposium “Immunometabolism at the Crossroads of Obesity and Cancer” to present recent research across the field of immunometabolism, with the setting of obesity and cancer as an ideal example of the complex interplay between metabolism, immunity, and cancer. Speakers highlighted new insights on the metabolic links between tumor cells and immune cells, with a focus on leveraging unique metabolic vulnerabilities of different cell types in the tumor microenvironment as therapeutic targets and demonstrated the effects of diet, the microbiome, and obesity on immune system function and cancer pathogenesis and therapy. Finally, speakers presented new technologies to interrogate the immune system and uncover novel metabolic pathways important for immunity.

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“…Of the 21 patients, 11 individuals (52%) achieved stable disease during the study [77]. There are multiple other IDH-targeted therapies in development [184]. In a phase II trial, the compound AG-120 is tested in patients with chondrosarcoma mutant IDH1.…”

Section: Targeted Treatmentmentioning

confidence: 99%

Dedifferentiated Chondrosarcoma from Molecular Pathology to Current Treatment and Clinical Trials

Zając,

Dróżdż,

Kisielewska

et al. 2023

Cancers

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Dedifferentiated chondrosarcoma (DDCS) is a rare subtype of chondrosarcoma, a primary cartilaginous malignant neoplasm. It accounts for up to 1–2% of all chondrosarcomas and is generally associated with one of the poorest prognoses among all chondrosarcomas with the highest risk of metastasis. The 5-year survival rates range from 7% to 24%. DDCS may develop at any age, but the average presentation age is over 50. The most common locations are the femur, pelvis humerus, scapula, rib, and tibia. The standard treatment for localised disease is surgical resection. Most patients are diagnosed in unresectable and advanced stages, and chemotherapy for localised and metastatic dedifferentiated DDCS follows protocols used for osteosarcoma.

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Recent advances of IDH1 mutant inhibitor in cancer therapy

Cited by 34 publications

References 104 publications

Mutated Isocitrate Dehydrogenase (mIDH) as Target for PET Imaging in Gliomas

Mutated Isocitrate Dehydrogenase (mIDH) as Target for PET Imaging in Gliomas

Immunometabolism at the crossroads of obesity and cancer—a Keystone Symposia report

Dedifferentiated Chondrosarcoma from Molecular Pathology to Current Treatment and Clinical Trials

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