Ivosidenib in IDH1-mutated cholangiocarcinoma: Clinical evaluation and future directions

Lavacchi, Daniele; Caliman, Enrico; Rossi, Gemma; Buttitta, Eleonora; Botteri, Cristina; Fancelli, Sara; Pellegrini, Elisa; Roviello, Giandomenico; Pillozzi, Serena; Antonuzzo, Lorenzo

doi:10.1016/j.pharmthera.2022.108170

Cited by 16 publications

(4 citation statements)

References 37 publications

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“…Drugs such as pemigatinib and futibatinib have shown enhanced OS in comparison to conventional chemotherapeutic treatments in ICC patients who have received prior treatment, with a median OS of approximately 20 months [30] . Additionally, there is a promising outlook for the combined utilization of mutation-targeted therapy and immunotherapy [39] . Immunotherapy, particularly immune checkpoint inhibitors, has shown remarkable success in ICC by exploiting the immune system's ability to recognize and attack cancer cells [63] .…”

Section: Discussionmentioning

confidence: 99%

“…IDH1 mutations have been identified in a subset of ICC cases, estimated to be approximately 15%-20% of cases [37] . These mutations result in the production of abnormal IDH enzymes that convert isocitrate to an abnormal metabolite, 2-hydroxyglutarate (2-HG), which accumulates in cancer cells and contributes to tumor growth and progression [38,39] .…”

Section: Isocitrate Dehydrogenase Inhibitorsmentioning

confidence: 99%

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Mutation-based therapies for intrahepatic cholangiocarcinoma: new options on the horizon

Pan,

Ye,

Zhou

et al. 2024

Hepatoma Res

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Intrahepatic cholangiocarcinoma (ICC), a rare but rising global malignancy originating from the bile ducts, poses significant challenges in terms of effective treatment and patient outcomes. While surgical excision remains the curative option, its limited efficacy necessitates more therapeutic strategies, including systemic therapies. The management of ICC involves a multidisciplinary approach, with treatment decisions guided by patient-specific and tumor-specific factors. Gemcitabine-cisplatin (GEMCIS) chemotherapy has been a standard first-line therapy, but recent advancements in immunotherapy, particularly the introduction of durvalumab, have provided new hope. Additionally, gene mutation-based therapies, targeting fibroblast growth factor receptors (FGFRs), isocitrate dehydrogenase-1 (IDH1), human epidermal growth factor receptor-2 (HER2), and B-RAF proto-oncogene (BRAF), offer promising prospects for personalized treatment. High-throughput genomic profiling technologies have facilitated the identification of actionable targets and the development of innovative therapeutic approaches. This review summarizes the mutation-based therapies in ICC, including FDA-approved targeted drugs and ongoing clinical trials, highlighting the evolving landscape of ICC treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Isocitrate Dehydrogenase Inhibitorsmentioning

confidence: 99%

Mutation-based therapies for intrahepatic cholangiocarcinoma: new options on the horizon

Pan,

Ye,

Zhou

et al. 2024

Hepatoma Res

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“…In cancer, epigenetic modifications silence chemokines such as CXCL9 and CXCL10 in the TME, enabling tumor immune evasion [ 104 ]. Gene mutations, such as the KRAS-G12D mutation and isocitrate dehydrogenase-1, can result in resistance to PD-1/PD-L1 immunotherapy in patients [ 105 , 106 ]. Activation of the Wnt-β-catenin signaling pathway may lead to immune tolerance [ 107 ].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Anti-Tumor Potential of Post-Translational Modifications of PD-1

Xi,

Zhao

2024

CIMB

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Programmed cell death protein-1 (PD-1) is a vital immune checkpoint molecule. The location, stability, and protein–protein interaction of PD-1 are significantly influenced by post-translational modification (PTM) of proteins. The biological information of PD-1, including its gene and protein structures and the PD-1/PD-L1 signaling pathway, was briefly reviewed in this review. Additionally, recent research on PD-1 post-translational modification, including the study of ubiquitination, glycosylation, phosphorylation, and palmitoylation, was summarized, and research strategies for PD-1 PTM drugs were concluded. At present, only a part of PD-1/PD-L1 treated patients (35–45%) are benefited from immunotherapies, and novel strategies targeting PTM of PD-1/PD-L1 may be important for anti-PD-1/PD-L1 non-responders (poor responders).

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“…The rst-line treatment in t patients is the combination of gemcitabine and cisplatin. Besides, with the improvement in the understanding of the molecular feature of cholangiocarcinoma, target therapy has been widely used, including isocitrate dehydrogenase-1 (IDH1), broblast growth factor receptor (FGFR) and ERBB2 (HER2/neu) [6,7]. Although such effort has been made to improve the treatment for this disease [8], cholangiocarcinoma remains to be a big challenge in medicine.…”

Section: Introductionmentioning

confidence: 99%

Genomic feature and potential therapeutic target for cholangiocarcinoma

Zheng

Shen

Jiang

et al. 2023

Preprint

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Background: The genomic feature of biliary tract carcinoma (BTC) has been characterized, but limited studies focus on the potential therapeutic target for cholangiocarcinoma patients. Methods: 43 BTC patients were enrolled in this retrospective study. Genomic characteristics including genomic alterations and mutational signatures were detected and analyzed. Then, the correlation between the genomic characteristics and clinicopathologic features was investigated. Next, the prognostic significance of these altered genes was evaluated. Besides, personalized targeted therapies for patients harboring potentially actionable targets (PATs) were investigated. Results: Among 43 patients, the genomic mutation was detected in 38 patients. Among these mutations, KRAS (44.2%), TP53(37.2%), ARID1A (18.6%), SMAD4(18.6%), BRCA2, CDKN2A (11.6%), and VEGFA (11.6%) are the most frequently altered cancer-related genes. Besides, germline mutations mainly occurred in ERBB, PI3K/AKT, MAPK, and RAS signaling. Among detected mutations, we found that TP53, STK11, MYC, and ERBB3 are gene alternations with significant prognostic values. In terms of potentially actionable target (PAT) analysis, 19 genes were proposed to be PATs in BTCs. and we found out that 79.1% of patients have Tier II somatic mutation in our cohort. Conclusions: The molecular feature is closely related to clinical characteristics in cholangiocarcinoma patients. In this study, we identified several commonly altered genes in cholangiocarcinoma patients and determined potential prognostic biomarkers and therapeutic targets for cholangiocarcinoma patients.

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Ivosidenib in IDH1-mutated cholangiocarcinoma: Clinical evaluation and future directions

Cited by 16 publications

References 37 publications

Mutation-based therapies for intrahepatic cholangiocarcinoma: new options on the horizon

Mutation-based therapies for intrahepatic cholangiocarcinoma: new options on the horizon

Anti-Tumor Potential of Post-Translational Modifications of PD-1

Genomic feature and potential therapeutic target for cholangiocarcinoma

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