Suramin for breast and prostate cancer: A pilot study of intermittent short infusions without adaptive control

Woll, Penella J.; Ranson, Malcolm R; Margison, Jennifer M; Thomson, Y; Water, Lisa van der; George, N. J. R.; Howell, Anthony

doi:10.1093/oxfordjournals.annonc.a058930

Cited by 9 publications

(3 citation statements)

References 13 publications

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“…We verified their resistance power against some cancer-related PTM sites (succinylation, ubiquitination, and phosphorylation) of hub proteins by molecular docking analysis and found their significant binding affinities. The literature review also supported our proposed ligands Suramin [171], Rifaximin [172], Telmisartan [173], Phenylpropan [174], Tukysa Tucatinib [175,176] Lynparza Olaparib [177], and TG.02 [14,178] as the candidate drug molecules for the treatment against BC. Therefore, the findings of this study might be promising and useful resources to wet-lab researchers and clinicians for further investigation to develop an early treatment plan against BC.…”

Section: Discussionsupporting

confidence: 66%

Robust Identification of Differential Gene Expression Patterns from Multiple Transcriptomics Datasets for Early Diagnosis, Prognosis, and Therapies for Breast Cancer

Tuly,

Hossen,

Islam

et al. 2023

Medicina

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Background and Objectives: Breast cancer (BC) is one of the major causes of cancer-related death in women globally. Proper identification of BC-causing hub genes (HubGs) for prognosis, diagnosis, and therapies at an earlier stage may reduce such death rates. However, most of the previous studies detected HubGs through non-robust statistical approaches that are sensitive to outlying observations. Therefore, the main objectives of this study were to explore BC-causing potential HubGs from robustness viewpoints, highlighting their early prognostic, diagnostic, and therapeutic performance. Materials and Methods: Integrated robust statistics and bioinformatics methods and databases were used to obtain the required results. Results: We robustly identified 46 common differentially expressed genes (cDEGs) between BC and control samples from three microarrays (GSE26910, GSE42568, and GSE65194) and one scRNA-seq (GSE235168) dataset. Then, we identified eight cDEGs (COL11A1, COL10A1, CD36, ACACB, CD24, PLK1, UBE2C, and PDK4) as the BC-causing HubGs by the protein-protein interaction (PPI) network analysis of cDEGs. The performance of BC and survival probability prediction models with the expressions of HubGs from two independent datasets (GSE45827 and GSE54002) and the TCGA (The Cancer Genome Atlas) database showed that our proposed HubGs might be considered as diagnostic and prognostic biomarkers, where two genes, COL11A1 and CD24, exhibit better performance. The expression analysis of HubGs by Box plots with the TCGA database in different stages of BC progression indicated their early diagnosis and prognosis ability. The HubGs set enrichment analysis with GO (Gene ontology) terms and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways disclosed some BC-causing biological processes, molecular functions, and pathways. Finally, we suggested the top-ranked six drug molecules (Suramin, Rifaximin, Telmisartan, Tukysa Tucatinib, Lynparza Olaparib, and TG.02) for the treatment of BC by molecular docking analysis with the proposed HubGs-mediated receptors. Molecular docking analysis results also showed that these drug molecules may inhibit cancer-related post-translational modification (PTM) sites (Succinylation, phosphorylation, and ubiquitination) of hub proteins. Conclusions: This study’s findings might be valuable resources for diagnosis, prognosis, and therapies at an earlier stage of BC.

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Section: Discussionsupporting

confidence: 66%

Robust Identification of Differential Gene Expression Patterns from Multiple Transcriptomics Datasets for Early Diagnosis, Prognosis, and Therapies for Breast Cancer

Tuly,

Hossen,

Islam

et al. 2023

Medicina

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“…29,30 Suramin has been used to treat prostate and breast cancers in clinical settings. 31,32 Recent experimental studies showed that it is also effective in attenuating muscle and liver fibrosis. 33,34 However, it remains unclear whether suramin has an antifibrotic effect in the kidney.…”

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confidence: 99%

Suramin Inhibits Renal Fibrosis in Chronic Kidney Disease

Liu

Tolbert

Pang

et al. 2011

Journal of the American Society of Nephrology

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The activation of cytokine and growth factor receptors associates with the development and progression of renal fibrosis. Suramin is a compound that inhibits the interaction of several cytokines and growth factors with their receptors, but whether suramin inhibits the progression of renal fibrosis is unknown. Here, treatment of cultured renal interstitial fibroblasts with suramin inhibited their activation induced by TGF-␤1 and serum. In a mouse model of obstructive nephropathy, administration of a single dose of suramin immediately after ureteral obstruction abolished the expression of fibronectin, largely suppressed expression of ␣-SMA and type I collagen, and reduced the deposition of extracellular matrix proteins. Suramin also decreased the expression of multiple cytokines including TGF-␤1 and reduced the interstitial infiltration of leukocytes. Moreover, suramin decreased expression of the type II TGF-␤ receptor, blocked phosphorylation of the EGF and PDGF receptors, and inactivated several signaling pathways associated with the progression of renal fibrosis. In a rat model of CKD, suramin abrogated proteinuria, limited the decline of renal function, and prevented glomerular and tubulointerstitial damage. Collectively, these findings indicate that suramin is a potent antifibrotic agent that may have therapeutic potential for patients with fibrotic kidney diseases.

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“…In different tumor entities suramin was proposed to bind to a range of growth factors such as the vascular endothelial growth factor or the epidermal growth factor [ 1 ]. Subsequently, suramin was tested in clinical trials of different metastatic tumor entities with emphasis on metastatic prostate cancer [ 4 , 5 , 6 , 7 ]. In line with the seemingly unspecific mode of action of suramin, the clinical application revealed several side effects such as coagulopathy, adrenal insufficiency, nephrotoxicity or hepatotoxicity [ 1 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies

et al. 2018

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Suramin is a trypan blue analogon originally developed to treat protozoan infections, which was found to have diverse antitumor effects. One of the most severe side effects in clinical trials was the development of a peripheral sensory-motor polyneuropathy. In this study, we aimed to investigate suramin-induced neuropathy with a focus on calcium (Ca2+) homeostasis as a potential pathomechanism. Adult C57Bl/6 mice treated with a single injection of 250 mg/kg bodyweight suramin developed locomotor and sensory deficits, which were confirmed by electrophysiological measurements showing a predominantly sensory axonal-demyelinating polyneuropathy. In a next step, we used cultured dorsal root ganglia neurons (DRGN) as an in vitro cell model to further investigate underlying pathomechanisms. Cell viability of DRGN was significantly decreased after 24-hour suramin treatment with a calculated IC50 of 283 µM. We detected a suramin-induced Ca2+ influx into DRGN from the extracellular space, which could be reduced with the voltage-gated calcium channel (VGCC) inhibitor nimodipine. Co-incubation of suramin and nimodipine partially improved cell viability of DRGN after suramin exposure. In summary, we describe suramin-induced neurotoxic effects on DRGN as well as potentially neuroprotective agents targeting intracellular Ca2+ dyshomeostasis.

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Suramin for breast and prostate cancer: A pilot study of intermittent short infusions without adaptive control

Abstract: We conclude that suramin can be safely and conveniently administered to outpatients by intermittent infusion without using complex adaptive dosing strategies. Suramin merits further study in less heavily pretreated breast cancer patients.

Cited by 9 publications

References 13 publications

Robust Identification of Differential Gene Expression Patterns from Multiple Transcriptomics Datasets for Early Diagnosis, Prognosis, and Therapies for Breast Cancer

Robust Identification of Differential Gene Expression Patterns from Multiple Transcriptomics Datasets for Early Diagnosis, Prognosis, and Therapies for Breast Cancer

Suramin Inhibits Renal Fibrosis in Chronic Kidney Disease

Suramin-Induced Neurotoxicity: Preclinical Models and Neuroprotective Strategies

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