Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(1), P. 148 - 175

Published: Jan. 20, 2023

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, most cases, it can only prolong life expectancy does not guarantee a complete cure. Furthermore, chemotherapy associated with severe adverse effects, one of the major complications effective In addition, newly published research outputs show that stem cells are involved disease progression, drug resistance, metastasis, recurrence they functional trans-differentiation capacity to response treatments. Novel strategies therefore required for better management The prime would be synthesize develop novel drugs need extensive resources, time, endurance brought into therapeutic use. subsequent screen anti-cancer activity available non-cancerous drugs. This concept repurposing non-cancer as alternative current therapy has become popular recent years because using existing anticancer several effects. Micronutrients have also been investigated due their significant effects negligible or no side availability food sources. this paper, we discuss ideal hypothesis screening activity, focus on clinical application treatment. Further, combination micronutrients target both cancers may result leading maximum tumor growth control.

Language: Английский

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Emerging Perspectives on the Antiparasitic Mebendazole as a Repurposed Drug for the Treatment of Brain Cancers

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1334 - 1334

Published: Jan. 10, 2023

Repurposing approved non-antitumor drugs is a promising and affordable strategy in drug discovery to identify new therapeutic uses different from the original medical indication that may help increase number of possible, effective anticancer drugs. The use ways other than their FDA-approved indications could offer novel avenues such as bypassing chemoresistance recurrence seen with conventional therapy treatment; moreover, it can safe economic for combination therapy. Recent works have demonstrated properties Mebendazole. This synthetic benzimidazole proved against broad spectrum intestinal Helminthiasis. Mebendazole penetrate blood-brain barrier has been shown inhibit malignant progression glioma by targeting signaling pathways related cell proliferation, apoptosis, or invasion/migration, increasing sensitivity cells chemotherapy radiotherapy. Moreover, several preclinical models ongoing clinical trials explore efficacy multiple cancers, including acute myeloid leukemia, brain cancer, oropharyngeal squamous carcinoma, breast gastrointestinal lung adrenocortical prostate head neck cancer. present review summarizes central literature regarding effects MBZ cancer lines, animal tumor models, suggest possible strategies economical combinations therapies might be an excellent candidate treatment tumors because its both when used monotherapy enhancement standard chemotherapeutics radiotherapy, due effectiveness on angiogenesis inhibition, cycle arrest, apoptosis induction, critical involved Hedgehog signaling. Therefore, attention repurposing recently increased potential versatility significant implications, reducing care costs optimizing existing therapies. Using treatments essential, particularly current therapeutics patients fail.

Language: Английский

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Advantages, Challenges, and Impact of Drug Repurposing for Cancer Treatment

IntechOpen eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Drug repurposing involves identifying new therapeutic uses for existing drugs, offering a cost-effective and time-efficient alternative to traditional drug discovery against cancer. Key approaches include computational, experimental, drug-centric strategies, which have demonstrated success in targeting specific cancer types such as colorectal with aspirin BCC itraconazole. Additionally, has shown potential combination therapies, enhancing treatment efficacy, preventing metastasis, disrupting metabolic processes cells, improving immunotherapy, overcoming resistance mechanisms. Despite its benefits, faces significant obstacles, including cancer’s biological complexity, clinical trial design challenges, intellectual property barriers, biases affecting outcomes, access knowledge. Cancer heterogeneity complicates the development of universally effective while high costs regulatory hurdles trials hinder rapid advancement. Furthermore, limited patent incentives reduce industry interest projects. AI is revolutionizing by targets predicting interactions, yet challenges related data quality, interpretability, computational requirements necessitate careful integration. To overcome these collaboration between academia, industry, bodies, alongside innovations bioinformatics methodologies, critical advancing viable strategy treatment. This chapter explore advantages, impacts, oncology, emphasizing accelerate therapies navigating obstacles necessity comprehensive validation.

Language: Английский

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USP5 Binds and Stabilizes EphA2 to Increase Nasopharyngeal Carcinoma Radioresistance

International Journal of Biological Sciences, Journal Year: 2025, Volume and Issue: 21(3), P. 893 - 909

Published: Jan. 6, 2025

Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment. However, the underlying mechanism of NPC radioresistance remains poorly understood, and promising radiosensitizer for radiotherapy is also lacked. Overexpression USP5 EphA2 has been linked to various cancers, both proteins have attracted considerable attention development new anti-cancer drugs. Here, we report that interacts with EphA2, increases protein stability expression by ubiquitin proteasome pathway cells. Mebendazole (MBZ), broad-spectrum anthelmintic drug, transcriptionally inhibits expression, then promotes ubiquitination degradation Functionally, enhances vitro vivo cell via stabilizing MBZ decreases targeting USP5/EphA2 axis. Moreover, levels are significantly higher radioresistant NPCs than those radiosensitive NPCs, predicting patient prognosis superior individual protein. These findings suggest binds stabilizes promote radioresistance, radiosensitivity axis, potential perhaps other cancers.

Language: Английский

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Molecular modelling of mebendazole polymorphs as a potential colchicine binding site inhibitor

New Journal of Chemistry, Journal Year: 2020, Volume and Issue: 44(33), P. 13990 - 13996

Published: Jan. 1, 2020

Form B of mebendazole is the form expected to bind more efficiently with colchicine binding site within tubulin protein.

Language: Английский

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Drug repurposing and relabeling for cancer therapy: Emerging benzimidazole antihelminthics with potent anticancer effects

Life Sciences, Journal Year: 2020, Volume and Issue: 258, P. 118189 - 118189

Published: Aug. 8, 2020

Language: Английский

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Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 12(2), P. 532 - 557

Published: Sept. 10, 2021

Drug repurposing or repositioning has been well-known to refer the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs increasingly becoming an attractive approach improve cancer therapy, with potentially lower overall costs and shorter timelines. Several by FDA have recently reported treat different types human cancers, aid some new emerging technologies, such as omics sequencing artificial intelligence overcome bottleneck repurposing. Therefore, in this review, we focus on summarizing potential drugs, including cardiovascular microbiological antibiotics, anti-viral anti-inflammatory anti-neurodegenerative antipsychotic antidepressants, cancers. We also discuss their novel targets relevant signaling pathways these old therapies. Taken together, inspiring findings will shed light more intricate molecular mechanisms future discovery.

Language: Английский

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Anthelmintics for drug repurposing: Opportunities and challenges

Saudi Pharmaceutical Journal, Journal Year: 2021, Volume and Issue: 29(5), P. 434 - 445

Published: April 19, 2021

Drug repositioning is defined as a process to identify new application for drugs. This approach critical it takes advantage of well-known pharmacokinetics, pharmacodynamics, and toxicity profiles the drugs; thus, chance their future failure decreases, cost development required time approval are reduced. Anthelmintics, which antiparasitic drugs, have recently demonstrated promising anticancer effects in vitro vivo. literature review focuses on potential anthelmintics treatment cancers. It also discusses pharmacokinetics pharmacodynamics proposed mechanisms, present conditions, challenges cancer therapy, strategies overcome these challenges.

Language: Английский

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Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 10

Published: Jan. 14, 2021

Cancer is a set of complex pathologies that has been recognized as major public health problem worldwide for decades. A myriad therapeutic strategies indeed available. However, the wide variability in tumor physiology, response to therapy, added multi-drug resistance poses enormous challenges clinical oncology. The last years have witnessed fast-paced development novel experimental and translational approaches therapeutics, supplemented with computational theoretical advances are opening promising avenues cope cancer defiances. At core these advances, there strong conceptual shift from gene-centric emphasis on driver mutations specific oncogenes suppressors—let us call silver bullet approach therapeutics—to systemic, semi-mechanistic based pathway perturbations global molecular physiological regulatory patterns—we will this shrapnel approach. still best one follow when clonal genes present patient, targeted therapies tackle those. Unfortunately, due heterogeneous nature tumors not common case. mutational level often reduced much smaller pathway-based dysfunctions evidenced by well-known hallmarks cancer. In such cases “shrapnel gunshots” may become more effective than “silver bullets”. Here, we briefly both abound discussion state art designs bioinformatics oncology perspective. Further depends building collaborative, multidisciplinary teams resort expertise oncologists, oncological surgeons, but also cell biologists pharmacologists, well bioinformaticians, data scientists. These be capable engaging cycle analyzing high-throughput experiments, mining databases, researching data, validating findings, improving outcomes benefits patients.

Language: Английский

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Exploring the molecular interaction of mebendazole with bovine serum albumin using multi-spectroscopic approaches and molecular docking

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: July 8, 2022

This article presents the binding interaction between mebendazole (MBZ) and bovine serum albumin. The has been studied using different techniques, such as fluorescence quenching spectroscopy, UV-visible synchronous fourier transform infrared, resonance energy transfer in addition to molecular docking. Results from Stern Volmer equation stated that for MBZ-BSA was static. spectroscopic study performed at three temperature settings. constant (kq), number of sites (n), thermodynamic parameters (ΔHο, ΔSο ΔGο), forces were determined. results exhibited endothermic. It revealed intermolecular hydrophobic led stabilization drug-protein system. Using site marker technique, MBZ BSA found be located subdomain IIA (site I). furtherly approved docking technique with most stable configuration. research may aid understanding pharmacokinetics toxicity give fundamental data its safe usage avoid toxicity.

Language: Английский

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