Concomitant Acute Tubular Necrosis and Acute Interstitial Nephritis Induced by Tipifarnib in a Patient with Squamous Cell Carcinoma of the Lung

Cruz, Paula Martínez de la; Shabaka, Amir; Mielgo-Rubio, Xabier; Guerrero-Márquez, Carmen; Giménez-Moyano, Sara; Fernández-Juárez, Gema

doi:10.1016/j.amjms.2021.04.003

Cited by 3 publications

(2 citation statements)

References 12 publications

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“…However, severe LUSC can block the trachea and cause obstructive lung function damage. Therefore, studies on LUSC should be strengthened ( Lindsay et al, 2021 ; Martinez de la Cruz et al, 2021 ; Pan et al, 2021 ). Several treatment options for LUAD are currently available; they include molecularly targeted therapy, immunotherapy, cytotoxic chemotherapy drug therapy, and a combination of these options.…”

Section: Introductionmentioning

confidence: 99%

“…Several treatment options for LUAD are currently available; they include molecularly targeted therapy, immunotherapy, cytotoxic chemotherapy drug therapy, and a combination of these options. Compared with LUAD, LUSC has fewer options for antitumor therapy ( Lindsay et al, 2021 ; Martinez de la Cruz et al, 2021 ; Pan et al, 2021 ). Therefore, LUSC-related studies should be expanded to discover new and more effective therapeutic intervention targets and realize safer and more effective anti-tumor drug treatment strategies for LUSC.…”

Section: Introductionmentioning

confidence: 99%

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A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs

Liu

Jia

et al. 2022

Front. Pharmacol.

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The transcription factor, sterol regulatory element binding protein 1 (SREBP-1), plays important roles in modulating the proliferation, metastasis, or resistance to antitumor agents by promoting cellular lipid metabolism and related cellular glucose-uptake/Warburg Effect. However, the underlying mechanism of SREBP-1 regulating the proliferation or drug-resistance in lung squamous cell carcinoma (LUSC) and the therapeutic strategies targeted to SREBP-1 in LUSC remain unclear. In this study, SREBP-1 was highly expressed in LUSC tissues, compared with the paired non-tumor tissues (the para-tumor tissues). A novel small-molecule inhibitor of SREBP-1, MSI-1 (Ma’s inhibitor of SREBP-1), based on natural product monomers, was identified by screening the database of natural products. Treatment with MSI-1 suppressed the activation of SREBP-1-related pathways and the Warburg effect of LUSC cells, as indicated by decreased glucose uptake or glycolysis. Moreover, treatment of MSI-1 enhanced the sensitivity of LUSC cells to antitumor agents. The specificity of MSI-1 on SREBP-1 was confirmed by molecular docking and point-mutation of SPEBP-1. Therefore, MSI-1 improved our understanding of SREBP-1 and provided additional options for the treatment of LUSC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs

Liu

Jia

et al. 2022

Front. Pharmacol.

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Omeprazole/tipifarnib

2021

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Combination of Tipifarnib and Sunitinib Overcomes Renal Cell Carcinoma Resistance to Tyrosine Kinase Inhibitors via Tumor-Derived Exosome and T Cell Modulation

Greenberg

Kim

Ahn

et al. 2022

Cancers

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Background: Tyrosine kinase inhibitors (TKI) were initially demonstrated as an efficacious treatment for renal cell carcinoma (RCC). However, after a median treatment length of 14 months, a vast majority of patients develop resistance. This study analyzed a combination therapy of tipifarnib (Tipi) + sunitinib that targeted exosome-conferred drug resistance. Methods: 786-O, 786-O-SR (sunitinib resistant), A498, A498-SR, Caki-2, Caki-2-SR, and 293T cells were cultured. Exosomes were collected using differential ultracentrifugation. Cell proliferation, Jurkat T cell immune assay, and immunoblot analysis were used for downstream analysis. Results: SR exosomes treatment displayed a cytotoxic effect on immune cells. This cytotoxic effect was associated with increased expression of PD-L1 on SR exosomes when compared to sunitinib-sensitive (SS) exosomes. Additionally, Tipi treatment downregulated PD-L1 expression on exosomes derived from SR cell lines. Tipi’s ability to downregulate PD-L1 in exosomes has a significant application within patients. Exosomes collected from patients with RCC showed increased PD-L1 expression over subjects without RCC. Next, exosome concentrations were then compared after Tipi treatment, with all SS cell lines displaying an even greater reduction. On immunoblot assay, 293T cells showed a dose-dependent increase in Alix with no change in either nSMase or Rab27a. Conversely, all the SS and SR cell lines displayed a decrease in all three markers. After a cell proliferation employed a 48-h treatment on all SS and SR cell lines, the drug combination displayed synergistic ability to decrease tumor growth. Conclusions: Tipifarnib attenuates both the exosome endosomal sorting complex required for endosomal sorting complex required for transport (ESCRT)-dependent and ESCRT-independent pathways, thereby blocking exosome biogenesis and secretion as well as downregulating PD-L1 on SS and SR cells.

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Concomitant Acute Tubular Necrosis and Acute Interstitial Nephritis Induced by Tipifarnib in a Patient with Squamous Cell Carcinoma of the Lung

Cited by 3 publications

References 12 publications

A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs

A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs

Omeprazole/tipifarnib

Combination of Tipifarnib and Sunitinib Overcomes Renal Cell Carcinoma Resistance to Tyrosine Kinase Inhibitors via Tumor-Derived Exosome and T Cell Modulation

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