Drug repurposing: An emerging strategy in alleviating skin cancer

Kumbhar, Popat; Kole, Kapil; Yadav, Tejashree; Bhavar, Ashwini; Waghmare, Pramod; Bhokare, Rajdeep; Manjappa, Arehalli S.; Jha, Niraj Kumar; Chellappan, Dinesh Kumar; Shinde, Sunita S.; Singh, Sachin Kumar; Dua, Kamal; Salawi, Ahmad; Disouza, John; Patravale, Vandana

doi:10.1016/j.ejphar.2022.175031

Cited by 12 publications

(5 citation statements)

References 178 publications

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“…347 Nanoparticles can minimize the systemic toxicity of traditional therapies, thereby significantly enhancing the ability of repurposed drugs to eliminate tumors without harming normal cells. 348 In this section, we catalog the various nano-carriers tailored for the targeted delivery of repurposed drugs against tumors, alongside ongoing clinical trials that are using nanomaterials to treat cancer.…”

Section: Drug Repurposing: Candidates For Nanomaterial-based Therapymentioning

confidence: 99%

Drug repurposing for cancer therapy

Xia,

Sun,

Huang

et al. 2024

Sig Transduct Target Ther

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Cancer, a complex and multifactorial disease, presents a significant challenge to global health. Despite significant advances in surgical, radiotherapeutic and immunological approaches, which have improved cancer treatment outcomes, drug therapy continues to serve as a key therapeutic strategy. However, the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects, and thus there remains a critical need to develop novel cancer therapeutics. One promising strategy that has received widespread attention in recent years is drug repurposing: the identification of new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective, proven to be safe, and can significantly expedite the drug development process due to their already established safety profiles. In light of this, the present review offers a comprehensive overview of the various methods employed in drug repurposing, specifically focusing on the repurposing of drugs to treat cancer. We describe the antitumor properties of candidate drugs, and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment. In addition, we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery. We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen. To conclude, we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

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Section: Drug Repurposing: Candidates For Nanomaterial-based Therapymentioning

confidence: 99%

Drug repurposing for cancer therapy

Xia,

Sun,

Huang

et al. 2024

Sig Transduct Target Ther

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“…A large number of preclinical studies have identified more than 200 conventional drugs with off-label anti-tumor effects and excellent reviews on this topic have been published recently [ 98 , 99 , 100 , 101 ]. Here, we summarize information about the most promising non-oncological repurposed drugs on track for clinical use that target receptors, signaling pathways, and proteins linking cancer hallmarks and microenvironment crosstalk.…”

Section: Prospects Of Drug Repurposingmentioning

confidence: 99%

Drug Repurposing at the Interface of Melanoma Immunotherapy and Autoimmune Disease

et al. 2022

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Cancer cells have a remarkable ability to evade recognition and destruction by the immune system. At the same time, cancer has been associated with chronic inflammation, while certain autoimmune diseases predispose to the development of neoplasia. Although cancer immunotherapy has revolutionized antitumor treatment, immune-related toxicities and adverse events detract from the clinical utility of even the most advanced drugs, especially in patients with both, metastatic cancer and pre-existing autoimmune diseases. Here, the combination of multi-omics, data-driven computational approaches with the application of network concepts enables in-depth analyses of the dynamic links between cancer, autoimmune diseases, and drugs. In this review, we focus on molecular and epigenetic metastasis-related processes within cancer cells and the immune microenvironment. With melanoma as a model, we uncover vulnerabilities for drug development to control cancer progression and immune responses. Thereby, drug repurposing allows taking advantage of existing safety profiles and established pharmacokinetic properties of approved agents. These procedures promise faster access and optimal management for cancer treatment. Together, these approaches provide new disease-based and data-driven opportunities for the prediction and application of targeted and clinically used drugs at the interface of immune-mediated diseases and cancer towards next-generation immunotherapies.

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“…Various non-oncology drugs including metformin (MFN), tadalafil (TDL), ketoconazole (KCZ), simvastatin (SVN), verapamil (VPL), and disulfiram (DSR), etc. have displayed potential anticancer activities against sorts of cancers including lung, liver, breast and melanoma [15][16][17][18][19][20]. Therefore, in the present research efforts have been made to preliminarily ascertain the in vitro and in silico anticancer activities of various non-oncology drug categories against human osteosarcoma cells, both singly and in combination.…”

Section: Introductionmentioning

confidence: 99%

In vitro, in silico and in vivo screening of non-oncology drugs for repurposing in osteosarcoma

DESAI¹,

MANJAPPA²,

KHULBE³

et al. 2023

jrp

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The first-line chemotherapy is associated with chief shortfalls such as non-specific distribution causing severe dose-dependent toxicities and development of tumor resistance. The current preliminary study aimed to identify the safe and effective non-oncology drugs as an alternative to toxic chemotherapeutics to treat osteosarcoma, and overcome new drug's shortage and development challenges. The different category non-oncology drugs (alone and in combinations) were screened for in vitro cytotoxicity behavior via MTT dye reduction assay and cell cycle arresting behavior using flow cytometer against human osteosarcoma (Saos-2 and MG-63) cells. The molecular docking of selected therapeutics was executed against cyclin-dependent kinase 1 (CDK1), cell cycle regulator overexpressed in cancer. The identified combination was further tested for in vivo toxicities in rats at two different doses. The current study revealed niclosamide (NSD), ketoconazole (KCZ), simvastatin (SVN) combination that causes substantial cytotoxicity (IC50 values are in picomoles) at 1:1:3 molar ratio when compared to other molar ratios. This combination has also caused substantial arrest of Saos-2 and MG-63 cells at S and G2/M phase. Additionally, all three drugs demonstrated better interaction with CDK1 indicating anticancer potential via inhibition of CDK1. Furthermore, the in vivo toxicity study revealed no significant changes in hematological and biochemical parameters, body weights of rats, weights of vital organs, daily food and water intake, and general behavior of rats. The obtained preliminary results revealed the potential application of this combination on non-oncology drugs in the safe and effective treatment of osteosarcoma. However, further in-depth studies are required before clinical application.

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Drug repurposing: An emerging strategy in alleviating skin cancer

Cited by 12 publications

References 178 publications

Drug repurposing for cancer therapy

Drug repurposing for cancer therapy

Drug Repurposing at the Interface of Melanoma Immunotherapy and Autoimmune Disease

In vitro, in silico and in vivo screening of non-oncology drugs for repurposing in osteosarcoma

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