The toxicity of nitrofuran compounds on melanoma and neuroblastoma cells is enhanced by Olaparib and ameliorated by melanin pigment

McNeil, Ewan M.; Ritchie, Ann-Marie; Melton, David W.

doi:10.1016/j.dnarep.2013.08.017

Cited by 15 publications

(8 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…24 Up to date, only 7 publications address the effect of nifurtimox or related nitrofurane compounds on neuroblastoma or medulloblastoma and still little is known about its mode of action in these malignancies. 22,37,38 In the present study, the cytotoxic effects and the induction of apoptosis in neuroblastoma cell lines is in accordance with previously published material. 23 Combination of 0.2 mM (84,3 ng/mL) topotecan (corresponding to therapeutic serum concentration in neuroblastoma patients 32 ) and nifurtimox in vitro showed significant reduction of cell viability at low nifurtimox concentration of 1 mg/mL, and significantly lowered cell viability compared to topotecan or nifurtimox alone.…”

Section: Discussionsupporting

confidence: 78%

Nifurtimox reduces N-Myc expression and aerobic glycolysis in neuroblastoma

Stanchi

Bruchelt

Handgretinger

et al. 2015

Cancer Biology & Therapy

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 78%

Nifurtimox reduces N-Myc expression and aerobic glycolysis in neuroblastoma

Stanchi

Bruchelt

Handgretinger

et al. 2015

Cancer Biology & Therapy

View full text Add to dashboard Cite

“…The topmost drug in our predicted shortlist, Crizotinib, a non-small cell lung cancer (NSCLC) drug, has been reported for its positive effect on melanoma by two studies (Surriga et Table 1, Bortezomib, is an approved drug for multiple myeloma that was suggested as a treatment for melanoma in combination therapy with temozolomide due to its ability to induce apoptosis and autophagic formation in human melanoma tumors (Amiri et al, 2004; Selimovic et al, 2013). Another FDA approved drug Olaparib (for breast and pancreatic carcinoma), was also found to be effective against melanoma by inhibiting repair of single-strand DNA breaks in different combination therapies (Czyż et al, 2016;McNeil et al, 2013).…”

Section: Identifying Drug Repositioning Candidatesmentioning

confidence: 99%

PS4DR: A multimodal workflow for identification and prioritization of drugs based on pathway signatures

Emon

Domingo‐Fernándéz

Hoyt

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: During the last decade, there has been a surge towards computational drug repositioning owing to constantly increasing -omics data in the biomedical research field. While numerous existing methods focus on the integration of heterogeneous data to propose candidate drugs, it is still challenging to substantiate their results with mechanistic insights of these candidate drugs. Therefore, there is a need for more innovative and efficient methods which can enable better integration of data and knowledge for drug repositioning. Results: Here, we present a customizable workflow ( PS4DR) which not only integrates high-throughput data such as genome-wide association study (GWAS) data and gene expression signatures from disease and drug perturbations but also takes pathway knowledge into consideration to predict drug candidates for repositioning. We have collected and integrated publicly available GWAS data and gene expression signatures for several diseases and hundreds of FDA-approved drugs or those under clinical trial in this study. Additionally, different pathway databases were used for mechanistic knowledge integration in the workflow. Using this systematic consolidation of data and knowledge, the workflow computes pathway signatures that assist in the prediction of new indications for approved and investigational drugs. Conclusion: We showcase PS4DR with applications demonstrating how this tool can be used for repositioning and identifying new drugs as well as proposing drugs that can simulate disease dysregulations. We were able to validate our workflow by demonstrating its capability to predict FDA-approved drugs for their known indications for several diseases. Further, PS4DR returned many potential drug candidates for repositioning that were backed up by epidemiological evidence extracted from scientific literature. Source code is freely available at https://github.com/ps4dr/ps4dr .

show abstract

“…The following drug inTable 1, Bortezomib, is an approved drug for multiple myeloma that was suggested as a treatment for melanoma in combination therapy with temozolomide due to its ability to induce apoptosis and autophagic formation in human melanoma tumors(Amiri et al, 2004;Selimovic et al, 2013). Another FDA approved drug Olaparib (for breast cancer), was also found to be effective against melanoma by inhibiting repair of single-strand DNA breaks in different combination therapies(Czyż et al, 2016;McNeil et al, 2013).The last two approved drugs in the list (i.e., Tivozanib for renal cell carcinoma and Belinostat for peripheral T-cell lymphoma) have been positively associated with a better response in melanoma(Gimsing et al, 2009;Friedman et al, 2015). Moreover, another mTOR inhibitor drug, Vistusertib (AZD-2014), currently in phase II clinical trial for meningioma, was reported to have a positive impact by mTORC1/2 inhibition of the resistance to MAPK pathway inhibitors in melanomas with high oxidative phosphorylation(Gopal et al, 2014;Schmid et al, 2017…”

mentioning

confidence: 99%

PS4DR: A multimodal workflow for identification and prioritization of drugs based on pathway signatures

Emon

Domingo‐Fernándéz

Hoyt

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: During the last decade, there has been a surge towards computational drug repositioning owing to constantly increasing -omics data in the biomedical research field. While numerous existing methods focus on the integration of heterogeneous data to propose candidate drugs, it is still challenging to substantiate their results with mechanistic insights of these candidate drugs. Therefore, there is a need for more innovative and efficient methods which can enable better integration of data and knowledge for drug repositioning.Results: Here, we present a customizable workflow (PS4DR) which not only integrates high-throughput data such as genome-wide association study (GWAS) data and gene expression signatures from disease and drug perturbations but also takes pathway knowledge into consideration to predict drug candidates for repositioning. We have collected and integrated publicly available GWAS data and gene expression signatures for several diseases and hundreds of FDA-approved drugs or those under clinical trial in this study. Additionally, different pathway databases were used for mechanistic knowledge integration in the workflow. Using this systematic consolidation of data and knowledge, the workflow computes pathway signatures that assist in the prediction of new indications for approved and investigational drugs. Conclusion: We showcase PS4DR with applications demonstrating how this tool can be used for repositioning and identifying new drugs as well as proposing drugs that can simulate disease dysregulations. We were able to validate our workflow by demonstrating its capability to predict FDA-approved drugs for their known indications for several diseases. Further, PS4DR returned many potential drug candidates for repositioning that were backed up by epidemiological evidence extracted from scientific literature. Source code is freely available at https://github.com/ps4dr/ps4dr.

show abstract

The toxicity of nitrofuran compounds on melanoma and neuroblastoma cells is enhanced by Olaparib and ameliorated by melanin pigment

Cited by 15 publications

References 38 publications

Nifurtimox reduces N-Myc expression and aerobic glycolysis in neuroblastoma

Nifurtimox reduces N-Myc expression and aerobic glycolysis in neuroblastoma

PS4DR: A multimodal workflow for identification and prioritization of drugs based on pathway signatures

PS4DR: A multimodal workflow for identification and prioritization of drugs based on pathway signatures

Contact Info

Product

Resources

About