Salinomycin-Based Drug Delivery Systems: Overcoming the Hurdles in Cancer Therapy

Tefas, Lucia Ruxandra; Barbălată, Cristina; Tefas, Cristian; Tomuță, Ioan

doi:10.3390/pharmaceutics13081120

Cited by 16 publications

(11 citation statements)

References 111 publications

(157 reference statements)

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“…This further suggests that salinomycin may share similar MOA with the AKT inhibitors, as indicated by their clustering in the tsne. Notably, salinomycin (specifically HSB-1216, delivered via QUATRAMER technology) has been granted orphan drug designation by the FDA in 2020, and a Phase I trial is planned for small cell lung cancer 42 – 44 . Further investigation would be of interest to uncover the potential utility of salinomycin for HNSCC treatment, and our discovery here may shed light into uncovering its MOA and enabling selection of patients with biomarker of response.…”

Section: Discussionmentioning

confidence: 99%

Uncovering drug repurposing candidates for head and neck cancers: insights from systematic pharmacogenomics data analysis

Chai

Tan

Cheong

2021

Sci Rep

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Effective treatment options for head and neck squamous cell carcinoma (HNSCC) are currently lacking. We exploited the drug response and genomic data of the 28 HNSCC cell lines, screened with 4,518 compounds, from the PRISM repurposing dataset to uncover repurposing drug candidates for HNSCC. A total of 886 active compounds, comprising of 418 targeted cancer, 404 non-oncology, and 64 chemotherapy compounds were identified for HNSCC. Top classes of mechanism of action amongst targeted cancer compounds included PI3K/AKT/MTOR, EGFR, and HDAC inhibitors. We have shortlisted 36 compounds with enriched killing activities for repurposing in HNSCC. The integrative analysis confirmed that the average expression of EGFR ligands (AREG, EREG, HBEGF, TGFA, and EPGN) is associated with osimertinib sensitivity. Novel putative biomarkers of response including those involved in immune signalling and cell cycle were found to be associated with sensitivity and resistance to MEK inhibitors respectively. We have also developed an RShiny webpage facilitating interactive visualization to fuel further hypothesis generation for drug repurposing in HNSCC. Our study provides a rich reference database of HNSCC drug sensitivity profiles, affording an opportunity to explore potential biomarkers of response in prioritized drug candidates. Our approach could also reveal insights for drug repurposing in other cancers.

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Section: Discussionmentioning

confidence: 99%

Uncovering drug repurposing candidates for head and neck cancers: insights from systematic pharmacogenomics data analysis

Chai

Tan

Cheong

2021

Sci Rep

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“…Salinomycin, however, has very high specificity towards CSCs because it targets ABC-binding transporters, as well as the Wnt/β-catenin, Hedgehog, Notch, and Akt signaling pathways—thus ensuring a direct treatment for all the aspects of stemness that hinder cancer treatment [ 317 , 318 ]. It also activates the p38 MAPK cascade which helps induce ROS-mediated apoptosis [ 319 , 320 ].…”

Section: Current Regimens For Cancer Therapymentioning

confidence: 99%

“…Despite its many promising properties in CSC targeting, administering salinomycin does come with certain obstacles—particularly in its aggressive hydrophilicity [ 318 , 324 ]. This entails a dependency on nanodelivery, which can hinder its long-term relevance as issues of toxicity and systemic flushing continue to stand in the way of NC-based therapeutic systems circulating the market [ 26 , 325 ].…”

Section: Current Regimens For Cancer Therapymentioning

confidence: 99%

Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

Nayak

Warrier

Kumar

2022

Stem Cell Rev and Rep

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The physiological state of the tumor microenvironment (TME) plays a central role in cancer development due to multiple universal features that transcend heterogeneity and niche specifications, like promoting cancer progression and metastasis. As a result of their preponderant involvement in tumor growth and maintenance through several microsystemic alterations, including hypoxia, oxidative stress, and acidosis, TMEs make for ideal targets in both diagnostic and therapeutic ventures. Correspondingly, methodologies to target TMEs have been investigated this past decade as stratagems of significant potential in the genre of focused cancer treatment. Within targeted oncotherapy, nanomedical derivates—nanocarriers (NCs) especially—have emerged to present notable prospects in enhancing targeting specificity. Yet, one major issue in the application of NCs in microenvironmental directed therapy is that TMEs are too broad a spectrum of targeting possibilities for these carriers to be effectively employed. However, cancer stem cells (CSCs) might portend a solution to the above conundrum: aside from being quite heavily invested in tumorigenesis and therapeutic resistance, CSCs also show self-renewal and fluid clonogenic properties that often define specific TME niches. Further scrutiny of the relationship between CSCs and TMEs also points towards mechanisms that underly tumoral characteristics of metastasis, malignancy, and even resistance. This review summarizes recent advances in NC-enabled targeting of CSCs for more holistic strikes against TMEs and discusses both the current challenges that hinder the clinical application of these strategies as well as the avenues that can further CSC-targeting initiatives. Graphical abstract Central role of CSCs in regulation of cellular components within the TME

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“…Salinomycin (SAL) is a polyether monocarboxylic acid produced by Streptomyces albus . In its native form, SAL (Figure e) is a chemical structure open to the extremes composed of carboxylic and hydroxyl moieties and able to form “head-to-tail” intramolecular hydrogen bonds . In this way, SAL can complex Na + /K + cations, resulting in concentration gradients and intracellular pH changes.…”

Section: Elements For Tumor-targeted Chemotherapeuticsmentioning

confidence: 99%

Carbon Nanotubes in Tumor-Targeted Chemotherapeutic Formulations: A Review of Opportunities and Challenges

Contreras‐Torres

Salas-Treviño

Soto‐Domínguez

et al. 2022

ACS Appl. Nano Mater.

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The research of carbon nanotubes (CNTs) has contributed to basic science and is playing leading roles in potential applications, including nanomedicine. In particular, CNTs have been proposed as nanocarriers for cancer therapeutics. This study reviews the advantages and potential challenges of using CNTs in chemotherapy drug-delivery formulations. We mainly focus on tumor-targeted systems prepared with hyaluronic acid and folic acid because of their biocompatibility, low cost, ease of conjugation to targeting agents, and specificity for pathologic cells. The relevance of these CNTs-based tumor-targeted drug-delivery systems is discussed for cisplatin, carboplatin, doxorubicin, gemcitabine, salinomycin, chlorin e6, and paclitaxel. An extensive and diversified list of methodologies for preparing these drug-delivery systems provides a rationale for definite protocols to attain comparability between conjugates prepared from different formulations. Hence, the scope of various CNTs-based tumor-targeted drug-delivery systems was reviewed from a perspective relating to the opportunities of using CNTs in chemotherapeutics and the challenges associated with developing formulations for human use.

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Salinomycin-Based Drug Delivery Systems: Overcoming the Hurdles in Cancer Therapy

Cited by 16 publications

References 111 publications

Uncovering drug repurposing candidates for head and neck cancers: insights from systematic pharmacogenomics data analysis

Uncovering drug repurposing candidates for head and neck cancers: insights from systematic pharmacogenomics data analysis

Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

Carbon Nanotubes in Tumor-Targeted Chemotherapeutic Formulations: A Review of Opportunities and Challenges

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