Editorial: FDA-Approved Drug Repositioning for P-Glycoprotein Overexpressing Resistant Cancer

Yoon, Sungpil; Wang, Xiaoju; Vongpunsawad, Sompong; Tromp, Gerard; Kuivaniemi, Helena

doi:10.3389/fonc.2021.632657

Cited by 6 publications

(4 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Drug repositioning is a popular practice for clinically used drugs [12,13]. Drug repositioning is advantageous as it leads to wider clinical applications for cancer patients without the performance of additional toxicity tests.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, novel mechanisms and inhibitors that target P-gp activity with low toxicity to normal cells were recognized. Therefore, our aim was to reposition drugs known for their toxicity with Food and Drug Administration (FDA) approval [12,13]. Once instances of novel, FDA-approved drug repositioning are found for sensitizing P-gp-overexpressing resistant cancers, we believe 2 of 13 that these drugs may be administered to patients with MDR cancer without the performance of further toxicity tests.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Low-Dose Rifabutin Increases Cytotoxicity in Antimitotic-Drug-Treated Resistant Cancer Cells by Exhibiting Strong P-gp-Inhibitory Activity

Lee

Kim

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

The cytotoxicity of various antibiotics at low doses in drug-resistant cancer cells was evaluated. Low doses of rifabutin were found to markedly increase the cytotoxicity of various antimitotic drugs, such as vincristine (VIC), to P-glycoprotein (P-gp)-overexpressing antimitotic-drug-resistant KBV20C cells. Rifabutin was also found to exert high levels of P-gp-inhibitory activity at 4 and 24 h posttreatment, suggesting that the cytotoxicity of VIC + rifabutin was mainly due to the direct binding of rifabutin to P-gp and the reduction of VIC efflux by P-gp. The combination of VIC + rifabutin also increased early apoptosis, G2 arrest, and the DNA damaging marker, pH2AX protein. Interestingly, only the combination of VIC + rifabutin induced remarkable levels of cytotoxicity in resistant KBV20C cells, whereas other combinations (VIC + rifampin, VIC + rifapentine, and VIC + rifaximin) induced less cytotoxicity. Such finding suggests that rifabutin specifically increases the cytotoxicity of VIC in KBV20C cells, independent of the toxic effect of the ansamycin antibiotic. Only rifabutin had high P-gp-inhibitory activity, which suggests that its high P-gp-inhibitory activity led to the increased cytotoxicity of VIC + rifabutin. As rifabutin has long been used in the clinic, repositioning this drug for P-gp-overexpressing resistant cancer could increase the availability of treatments for patients with drug-resistant cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low-Dose Rifabutin Increases Cytotoxicity in Antimitotic-Drug-Treated Resistant Cancer Cells by Exhibiting Strong P-gp-Inhibitory Activity

Lee

Kim

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…The study focuses on a Food and Drug Administration (FDA)-approved JAK2 inhibitor by exploring a drug repositioning strategy. As the FDA provides easily accessible data on the beneficial and adverse effects of numerous drugs used in humans over a prolonged period, this could lower the costs and speed up the process of developing drugs to treat patients with drug-resistant cancer, as repeating a large number of toxicity tests could be circumvented [ 2 , 3 ]. Although JAK2 inhibitors have previously been reported to exhibit P-gp inhibitory activity, this study is the first to demonstrate that the FDA-approved JAK2 inhibitor fedratinib has P-gp inhibitory activity and a low dose can be combined with chemotherapeutic drugs.…”

mentioning

confidence: 99%

Contribution of Cancer-Targeting Drugs toward Faster Clinical Application

Yoon

Kim²

2022

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, the incidence of cancer is higher in patients with diabetes than in individuals who do not have diabetes (1). Metformin, a well-known antidiabetic drug, has been associated with anticancer effects and can be considered as a repositioned drug (2). Several studies have shown that metformin has benefits over other drugs in reducing the incidence of cancer in patients with diabetes (3,4), implying that apart from its usage as an anti-diabetic drug, it can be used for new indications, in this case, as a drug for the prevention of cancer.…”

mentioning

confidence: 99%

Drug Repositioning With an Anticancer Effect: Contributions to Reduced Cancer Incidence in Susceptible Individuals

Yoon

Kim

2021

In Vivo

Self Cite

View full text Add to dashboard Cite

Certain diseases and age groups are associated with a higher incidence of cancer. Cancer prevention can be achieved using repositioned drugs that have anticancer ability, thereby reducing the incidence of cancer in susceptible individuals. This implies that the selection of repositioned drugs can have dual benefits: controlling preexisting diseases and facilitating cancer prevention. This report outlines the rationale underlying drug repositioning for medications with an anticancer effect and discusses its advantages. We discuss repositioned drugs with anticancer effects that may contribute to cancer prevention in susceptible individuals and the general population with temporary, treatable conditions. The discussion of drug repositioning in this review should facilitate the initiation of clinical trials and lead to therapeutic application of such drugs to reduce the incidence of cancer in susceptible individuals.Patients with human immunodeficiency virus (HIV). It has been observed that patients with HIV have a higher incidence of 3039 This article is freely accessible online.

show abstract

Editorial: FDA-Approved Drug Repositioning for P-Glycoprotein Overexpressing Resistant Cancer

Cited by 6 publications

References 13 publications

Low-Dose Rifabutin Increases Cytotoxicity in Antimitotic-Drug-Treated Resistant Cancer Cells by Exhibiting Strong P-gp-Inhibitory Activity

Low-Dose Rifabutin Increases Cytotoxicity in Antimitotic-Drug-Treated Resistant Cancer Cells by Exhibiting Strong P-gp-Inhibitory Activity

Contribution of Cancer-Targeting Drugs toward Faster Clinical Application

Drug Repositioning With an Anticancer Effect: Contributions to Reduced Cancer Incidence in Susceptible Individuals

Contact Info

Product

Resources

About