Anticancer Properties of Fenofibrate: A Repurposing Use

Lian, Xin; Wang, Gang; Zhou, Honglan; Zheng, Zongyu; Fu, Yue; Cai, Lu

doi:10.7150/jca.24488

Cited by 61 publications

(73 citation statements)

References 90 publications

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“…However, these studies were all conducted in rodents. Some investigators noted that rodent livers have a higher PPAR expression than do human livers . Our study is the first epidemiological study exploring the relationship between fibrate use and liver cancer.…”

Section: Discussionmentioning

confidence: 75%

“…In patients with hyperlipidemia, they selectively activate the peroxisome proliferator‐activated receptor‐α (PPAR‐α), reduce triglyceride levels, and increase high‐density lipoprotein concentrations . Recent accumulating biological evidence has suggested that PPAR‐α is vital in human cancer development and that fibrates are involved in cancer cell apoptosis, cell‐cycle arrest, and migration, making them prospective anticancer agents. Some experimental studies have further indicated that fibrates may reduce hepatocellular carcinoma cell proliferation via PPAR‐α–associated mechanisms .…”

mentioning

confidence: 99%

“…Conversely, a few in vivo studies have observed that a fibrate might function as a liver tumor promoter . However, PPAR expression in rodents and humans differs considerably . The association between fibrate usage and subsequent liver cancer risk in humans remains unclear.…”

mentioning

confidence: 99%

“…[25][26][27] However, PPAR expression in rodents and humans differs considerably. 23 The association between fibrate usage and subsequent liver cancer risk in humans remains unclear. Therefore, this epidemiological study investigated the potential relationship between fibrate use and liver cancer risk using population-based claim data in Taiwan by applying a propensity score-matching design.…”

mentioning

confidence: 99%

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Inverse Association of Fibrates and Liver Cancer: A Population‐Based Case‐Control Study in Taiwan

Shih

Tsai

et al. 2019

The Journal of Clinical Pharma

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This large‐scale case‐control study in Taiwan elucidated the potential connection between fibrate use and liver cancer by using the Longitudinal Health Insurance Database 2005 with a propensity‐score–matching design. In total, 4173 patients diagnosed as having liver cancer were included as cases, and 4173 propensity‐score–matched patients without liver cancer were identified as controls. The association between previous fibrate use and liver cancer occurrence was demonstrated using conditional logistic regression. Fibrate use was noted in 371 (8.89%) cases and 481 (11.53%) controls. After adjustments, the cases had significantly lower odds of previous fibrate use than did the controls (adjusted odds ratio 0.70, 95%CI 0.60‐0.82); moreover, regardless of the patients’ sex, age group, and comorbidities, the cases were less likely to have used fibrates than were the controls. Dose‐dependent analysis revealed that 1‐695 cumulative defined daily doses of fibrates may significantly induce a protective effect for liver cancer. Although other fibrate dose intervals did not reach statistical significance, the dose‐response curve presented the trend of a protective effect for liver cancer among the fibrate users. In summary, fibrate use had a significant protective effect against liver cancer in this Asian population.

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Section: Discussionmentioning

confidence: 75%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Inverse Association of Fibrates and Liver Cancer: A Population‐Based Case‐Control Study in Taiwan

Shih

Tsai

et al. 2019

The Journal of Clinical Pharma

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“…Other drugs such as L-NMMA (tilarginine acetate, a nitric oxide synthase inhibitor) [138], pro-viral integration moloney virus kinase (PIM)-1 inhibitors (olaparib) [139], L-asparginase [140], and fenofibrate [141] are being repurposed for breast cancer. These drugs were originally used in patients with cardiogenic shock, against viral infection, leukemia, helminthic infection, and in patients with high serum cholesterol and triglycerides, respectively.…”

Section: Future Perspectives and Challengesmentioning

confidence: 99%

Drug repurposing for breast cancer therapy: Old weapon for new battle

Aggarwal

Verma

Aggarwal

et al. 2021

Seminars in Cancer Biology

105

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Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process of drug repurposing. Repositioning approach not only fastens the process of drug development but also offers more effective, cheaper, safer drugs with lesser/known side effects. During the last decade, drugs such as alkylating agents, anthracyclins, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors has been repositioned for breast cancer treatment. The repositioned drugs have been successfully used for the treatment of most aggressive triple negative breast cancer. The literature review suggest that serendipity plays a major role in the drug development. This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed. Current breast cancer therapyUnlike a decade ago, clinicians today have multiple choices for breast cancer treatment depending on the size, stage, grade, metastatic behavior, aggressiveness and intrinsic molecular subtyping of tumor, age, menopausal status, overall health, comorbidities, and preferences of the patient [9-13]. Chemotherapy, hormone therapy, immunotherapy, radiotherapy, and surgery are the common modalities for breast cancer [10,14]. Primary choice of treatment usually includes surgery with the aim of complete resection of the major tumor mass on the first hand. Breast conserving (lumpectomy) and breast reconstruction surgeries, mastectomy or lymph node dissections are performed initially in the breast cancer patients [15]. Surgery may be preceded with the systemic neoadjuvant therapies in order to shrink the tumor for effective surgery and to maximize breast conservation. For example, in HER2+ cases, Trastuzumab (Herceptin) and Pertuzumab (Perjeta)

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US FDA‐Approved Small‐Molecule Kinase Inhibitors for Cancer Therapy

Tadesse

Wang

2021

Burger's Medicinal Chemistry and Drug Discovery

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Abnormal activation of kinases is associated with various types of human cancer. A milestone approval of a small‐molecule kinase inhibitor (SMKI), imatinib, in 2001 for the treatment of chronic myeloid leukemia has revolutionized the clinical practice. This has invigorated the kinase‐targeted drug discovery and clinical sciences, and drug developers have been searching for the next revolutionary therapeutic agents to combat cancer. By mid‐2019, a total of 48 SMKIs have received their regulatory approvals from the United States Food and Drug Administration (USFDA) for the treatment of cancer. This article starts with an introduction of kinases; emphasis is placed on the differences between the structures of active and inactive kinases in that these structural disparities form the basis of the current classification of SMKIs which is subsequently outlined. Thereafter USFDA‐approved SMKI oncology drugs are delineated, with a great deal of attention paid to their respective oncology indications and co‐crystal structures with indication‐related kinases; an overview of biomedical rationales of the kinases being targeted is also provided. Towards the end, some of the current challenges and future prospects in developing SMKI‐based cancer therapies are discussed.

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Anticancer Properties of Fenofibrate: A Repurposing Use

Cited by 61 publications

References 90 publications

Inverse Association of Fibrates and Liver Cancer: A Population‐Based Case‐Control Study in Taiwan

Inverse Association of Fibrates and Liver Cancer: A Population‐Based Case‐Control Study in Taiwan

Drug repurposing for breast cancer therapy: Old weapon for new battle

US FDA‐Approved Small‐Molecule Kinase Inhibitors for Cancer Therapy

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