A Wnt/β-catenin signaling inhibitor, IMU1003, suppresses the emergence of osimertinib-resistant colonies from gefitinib-resistant non-small cell lung cancer cells

Katagiri, Hiroshi; Yonezawa, Honami; Shitamura, Sho; Sugawara, Aoi; Kawano, Tomikazu; Maemondo, Makoto; Nishiya, Naoyuki

doi:10.1016/j.bbrc.2023.01.018

Cited by 3 publications

(4 citation statements)

References 21 publications

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“…Ethacrynic acid, a loop diuretic, suppresses EMT of A549 cells via blocking of NDP-induced Wnt signaling [ 245 ] (Table 5 ). IMU1003 is an atrarate derivative which dramatically decreased the emergence of osimertinib-resistant colonies through inhibiting the nuclear localization of β-catenin [ 246 ] (Table 5 ).…”

Section: Potential Nsclc Treatments Through Suppression Of Wnt/β‑cate...mentioning

confidence: 99%

Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer

Zhang,

Westover,

Tang

et al. 2024

J Transl Med

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Wnt/β-catenin signaling is a critical pathway that influences development and therapeutic response of non-small cell lung cancer (NSCLC). In recent years, many Wnt regulators, including proteins, miRNAs, lncRNAs, and circRNAs, have been found to promote or inhibit signaling by acting on Wnt proteins, receptors, signal transducers and transcriptional effectors. The identification of these regulators and their underlying molecular mechanisms provides important implications for how to target this pathway therapeutically. In this review, we summarize recent studies of Wnt regulators in the development and therapeutic response of NSCLC.

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Section: Potential Nsclc Treatments Through Suppression Of Wnt/β‑cate...mentioning

confidence: 99%

Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer

Zhang,

Westover,

Tang

et al. 2024

J Transl Med

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“…β‐Catenin is a key signaling protein factor in the classical Wnt signaling pathway 76 . β‐Catenin was originally discovered as an adhesion factor, under normal physiological conditions, most of the β‐catenin molecules in the cytoplasm are bound to E‐cadherin present in the cell membrane to mediate adhesion between cells 77 . Later on, β‐catenin was identified as a multifunctional protein with important effects on normal human physiological functions 78 .…”

Section: Signaling Pathways In Osmentioning

confidence: 99%

“… 76 β‐Catenin was originally discovered as an adhesion factor, under normal physiological conditions, most of the β‐catenin molecules in the cytoplasm are bound to E‐cadherin present in the cell membrane to mediate adhesion between cells. 77 Later on, β‐catenin was identified as a multifunctional protein with important effects on normal human physiological functions. 78 Whether or not β‐catenin acts via the accumulation of β‐catenin signals is the main basis for distinguishing between classical and nonclassical pathways.…”

Section: Signaling Pathways In Osmentioning

confidence: 99%

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

Shen

Lan

et al. 2023

MedComm

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Osteosarcoma (OS) is a highly prevalent bone malignancy among adolescents, accounting for 40% of all primary malignant bone tumors. Neoadjuvant chemotherapy combined with limb‐preserving surgery has effectively reduced patient disability and mortality, but pulmonary metastases and OS cells' resistance to chemotherapeutic agents are pressing challenges in the clinical management of OS. There has been an urgent need to identify new biomarkers for OS to develop specific targeted therapies. Recently, the continued advancements in genomic analysis have contributed to the identification of clinically significant molecular biomarkers for diagnosing OS, acting as therapeutic targets, and predicting prognosis. Additionally, the contemporary molecular classifications have revealed that the signaling pathways, including Wnt/β‐catenin, PI3K/AKT/mTOR, JAK/STAT3, Hippo, Notch, PD‐1/PD‐L1, MAPK, and NF‐κB, have an integral role in OS onset, progression, metastasis, and treatment response. These molecular classifications and biological markers have created new avenues for more accurate OS diagnosis and relevant treatment. We herein present a review of the recent findings for the modulatory role of signaling pathways as possible biological markers and treatment targets for OS. This review also discusses current OS therapeutic approaches, including signaling pathway‐based therapies developed over the past decade. Additionally, the review covers the signaling targets involved in the curative effects of traditional Chinese medicines in the context of expression regulation of relevant genes and proteins through the signaling pathways to inhibit OS cell growth. These findings are expected to provide directions for integrating genomic, molecular, and clinical profiles to enhance OS diagnosis and treatment.

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“…Importantly, inhibiting multiple elements of the canonical Wnt pathway can dramatically increase the in vitro and in vivo effectiveness of EGFR inhibitors ( Casás-Selves et al, 2012 ; Scarborough et al, 2017 ; Yan et al, 2022 ). Furthermore, pharmacological reduction of β-catenin nuclear localization inhibited resistance to osimertinib (a third-generation EGFR-TKI) in PC-9 cells resistant to gefitinib (a first-generation EGFR-TKI), and IMU1003, an inhibitor of nuclear localization of β-catenin, significantly reduced the emergence of osimertinib-resistant colonies ( Katagiri et al, 2023 ). This implies that inhibition of nuclear β-catenin function may overcome transgenerational EGFR-TKI resistance.…”

Section: Wnt/β-catenin In Lcmentioning

confidence: 99%

Natural compounds: Wnt pathway inhibitors with therapeutic potential in lung cancer

Shen,

Gao,

et al. 2023

Front. Pharmacol.

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The Wnt/β-catenin pathway is abnormally activated in most lung cancer tissues and considered to be an accelerator of carcinogenesis and lung cancer progression, which is closely related to increased morbidity rates, malignant progression, and treatment resistance. Although targeting the canonical Wnt/β-catenin pathway shows significant potential for lung cancer therapy, it still faces challenges owing to its complexity, tumor heterogeneity and wide physiological activity. Therefore, it is necessary to elucidate the role of the abnormal activation of the Wnt/β-catenin pathway in lung cancer progression. Moreover, Wnt inhibitors used in lung cancer clinical trials are expected to break existing therapeutic patterns, although their adverse effects limit the treatment window. This is the first study to summarize the research progress on various compounds, including natural products and derivatives, that target the canonical Wnt pathway in lung cancer to develop safer and more targeted drugs or alternatives. Various natural products have been found to inhibit Wnt/β-catenin in various ways, such as through upstream and downstream intervention pathways, and have shown encouraging preclinical anti-tumor efficacy. Their diversity and low toxicity make them a popular research topic, laying the foundation for further combination therapies and drug development.

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A Wnt/β-catenin signaling inhibitor, IMU1003, suppresses the emergence of osimertinib-resistant colonies from gefitinib-resistant non-small cell lung cancer cells

Cited by 3 publications

References 21 publications

Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer

Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

Natural compounds: Wnt pathway inhibitors with therapeutic potential in lung cancer

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