The Future of HER2-Targeted Treatment for Osteosarcoma: Lessons from the Negative Trastuzumab Deruxtecan Results

Nakano, Kenji

doi:10.3390/ijms242316823

Cited by 3 publications

(1 citation statement)

References 82 publications

(89 reference statements)

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“…VEGF is a typical NF-κB target [ 129 ], which also represents an effector of VEGFR signaling [ 130 ]. Likewise, NF-κB-mediated HER2 overexpression is involved in radiation-induced repopulation in heterogeneous tumors [ 131 ]; this RTK is amplified in ~30% of patients with OS [ 132 ].…”

Section: Nf-κb Dysregulation and Cancermentioning

confidence: 99%

Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity

Medeiros,

Guenka,

Bastos

et al. 2024

Pharmaceuticals

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Tumor heterogeneity poses a significant challenge in osteosarcoma (OS) treatment. In this regard, the “omics” era has constantly expanded our understanding of biomarkers and altered signaling pathways (i.e., PI3K/AKT/mTOR, WNT/β-catenin, NOTCH, SHH/GLI, among others) involved in OS pathophysiology. Despite different players and complexities, many commonalities have been described, among which the nuclear factor kappa B (NF-κB) stands out. Its altered activation is pervasive in cancer, with pleiotropic action on many disease-relevant traits. Thus, in the scope of this article, we highlight the evidence of NF-κB dysregulation in OS and its integration with other cancer-related pathways while we summarize the repertoire of compounds that have been described to interfere with its action. In silico strategies were used to demonstrate that NF-κB is closely coordinated with other commonly dysregulated signaling pathways not only by functionally interacting with several of their members but also by actively participating in the regulation of their transcription. While existing inhibitors lack selectivity or act indirectly, the therapeutic potential of targeting NF-κB is indisputable, first for its multifunctionality on most cancer hallmarks, and secondly, because, as a common downstream effector of the many dysregulated pathways influencing OS aggressiveness, it turns complex regulatory networks into a simpler picture underneath molecular heterogeneity.

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Section: Nf-κb Dysregulation and Cancermentioning

confidence: 99%

Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity

Medeiros,

Guenka,

Bastos

et al. 2024

Pharmaceuticals

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Unraveling molecular aberrations and pioneering therapeutic strategies in osteosarcoma

Yan,

Wang,

Yue

et al. 2024

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Desmoplastic small round cell tumor: from genomics to targets, potential paths to future therapeutics

Magrath,

Espinosa-Cotton,

Flinchum

et al. 2024

Front. Cell Dev. Biol.

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Desmoplastic Small Round Cell Tumor (DSRCT) is a highly aggressive pediatric cancer caused by a reciprocal translocation between chromosomes 11 and 22, leading to the formation of the EWSR1::WT1 oncoprotein. DSRCT presents most commonly in the abdominal and pelvic peritoneum and remains refractory to current treatment regimens which include chemotherapy, radiotherapy, and surgery. As a rare cancer, sample and model availability have been a limiting factor to DSRCT research. However, the establishment of rare tumor banks and novel cell lines have recently propelled critical advances in the understanding of DSRCT biology and the identification of potentially promising targeted therapeutics. Here we review model and dataset availability, current understanding of the EWSR1::WT1 oncogenic mechanism, and promising preclinical therapeutics, some of which are now advancing to clinical trials. We discuss efforts to inhibit critical dependencies including NTRK3, EGFR, and CDK4/6 as well as novel immunotherapy strategies targeting surface markers highly expressed in DSRCT such as B7-H3 or neopeptides either derived from or driven by the fusion oncoprotein. Finally, we discuss the prospect of combination therapies and strategies for prioritizing clinical translation.

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The Future of HER2-Targeted Treatment for Osteosarcoma: Lessons from the Negative Trastuzumab Deruxtecan Results

Cited by 3 publications

References 82 publications

Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity

Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity

Unraveling molecular aberrations and pioneering therapeutic strategies in osteosarcoma

Desmoplastic small round cell tumor: from genomics to targets, potential paths to future therapeutics

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