Effects of bexarotene: A Synthesis of Findings from 24 Studies

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Original Abstract of the Article

Major Research Findings

Bexarotene, a retinoid X receptor (RXR) agonist, has shown promise as a therapeutic agent for various diseases in multiple studies. 8 suggests that silicon-containing analogs of bexarotene, while not regulating the differentiation of human pluripotent stem cells, may possess enhanced functions over the parent compound bexarotene, such as induction and regulation of cell death and cell numbers. 20 found that bexarotene improves the function of human osteoblasts by suppressing LPS-induced inflammation, activating autophagy, and suppressing the NLRP3 inflammasome. 11 demonstrated that MSU42011, an analog of bexarotene, exhibits immunomodulatory and anti-tumor effects in preclinical models of HER2+ breast cancer and Kras-driven lung cancer. 4 evaluates the safety and toxicity of topical bexarotene as a potential chemoprevention agent for women at high risk for breast cancer. Additionally, bexarotene is showing potential in the prevention and treatment of Alzheimer’s disease. 24 suggests that bexarotene may suppress oxidative stress and apoptosis induced by Aβ(1-42) in rat synaptosomes.

Benefits and Risks

Benefit Summary

Multiple studies highlight the beneficial effects of bexarotene in various areas, including cancer prevention and treatment, neurodegenerative diseases, inflammation suppression, and activation of autophagy. Bexarotene is effective in treating cutaneous T-cell lymphoma, and 1 shows that compared to brentuximab vedotin, bexarotene significantly improved objective response rates and progression-free survival in patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma. 23 found that bexarotene inhibits AGE-induced degradation of the articular extracellular matrix, suggesting potential for preventing and treating osteoarthritis. 16 demonstrates that bexarotene exhibits neuroprotective effects in a mouse model of cerebral ischemia-reperfusion injury by inhibiting the JIP3/ASK1/JNK/Caspase 3 signaling pathway. 5 shows that bexarotene may activate the LKB1 signaling pathway, offering promise for the prevention and treatment of cardiovascular diseases. 12 shows that bexarotene inhibits cell proliferation in C6 glioma cells by inducing oxidative stress, DNA damage, and apoptosis through the PPARγ/NF-κB signaling pathway. 17 suggests that bexarotene may be effective in treating Cushing’s disease as an antagonist of the TR4 nuclear receptor, suppressing proopiomelanocortin signaling. 9 demonstrates that bexarotene can enhance lenalidomide's anti-myeloma activity and improve T-cell function, while maintaining its glucose-lowering effects. 3 suggests that the combination of bexarotene and sulindac may effectively prevent intestinal carcinogenesis in familial adenomatous polyposis. 6 found that bexarotene promotes axon sprouting and increases microglia/macrophage-specific BDNF expression after traumatic brain injury. Bexarotene shows potential to contribute to the prevention and treatment of various diseases through these actions.

Risk Summary

Bexarotene is not without its risks. 18 reveals that bexarotene causes fetal atrophy and bone dysplasia in rats, indicating potential teratogenicity. Additionally, bexarotene may impact various organs and tissues, including the liver, skin, and visual system. Therefore, careful monitoring for potential side effects is crucial when using bexarotene, and it should only be used under a doctor’s supervision.

Comparison of Studies

Commonalities

These studies generally agree that bexarotene holds significant potential as a therapeutic agent for a wide range of diseases. Specifically, bexarotene exhibits beneficial effects in areas such as cancer, neurodegenerative diseases, inflammation, and autophagy. These findings collectively suggest the broad therapeutic potential of bexarotene and warrant further research and development in the field.

Differences

These studies also highlight the diverse mechanisms of action and effects of bexarotene depending on the disease and cell type. For example, 10 shows that bexarotene's remyelination efficacy is age-dependent. 2 explores the potential of bexarotene analogs as selective RXR agonists for various diseases. These findings suggest that developing tailored treatment approaches for individual patients is crucial to maximize the therapeutic benefits of bexarotene.

Consistency and Contradictions in Results

While multiple studies point to the therapeutic potential of bexarotene in various diseases, the mechanisms of action and efficacy can vary depending on the specific disease and cell type. Therefore, developing individualized treatment plans is essential for maximizing the therapeutic benefits of bexarotene. Additionally, careful consideration of the safety profile of bexarotene is necessary due to potential side effects.

Real-Life Applications and Caveats

Bexarotene is currently approved for the treatment of cutaneous T-cell lymphoma. Further research is necessary to evaluate the effectiveness of bexarotene in treating other diseases. Given the potential side effects of bexarotene, it is crucial to follow a doctor's instructions carefully and monitor for any adverse reactions. Bexarotene should only be used under a doctor’s supervision.

Limitations of Current Research

Research on bexarotene is still ongoing, and further studies are needed. Specifically, more research is required to understand the mechanisms of action and efficacy of bexarotene in various diseases and cell types, as well as to mitigate potential side effects.

Future Research Directions

Future research should focus on elucidating the mechanisms of action and efficacy of bexarotene, leading to the development of personalized treatment strategies for individual patients. Further research is also needed to reduce potential side effects associated with bexarotene. Additionally, exploring new applications for bexarotene is encouraged.

Conclusion

Bexarotene holds significant promise as a therapeutic agent for various diseases, and further research is warranted. However, it's important to remember that bexarotene can cause side effects. Always consult your doctor and follow their instructions carefully if you are prescribed bexarotene.

Literature analysis of 24 papers
Positive Content
23
Neutral Content
1
Negative Content
0
Article Type
1
0
0
2
24
1.

Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T-cell lymphoma: final data.

Author: HorwitzSteven M, ScarisbrickJulia J, DummerReinhard, WhittakerSean, DuvicMadeleine, KimYoun H, QuaglinoPietro, ZinzaniPier Luigi, BechterOliver, EradatHerbert, Pinter-BrownLauren, AkilovOleg E, GeskinLarisa, SanchesJose A, Ortiz-RomeroPablo L, WeichenthalMichael, FisherDavid C, WalewskiJan, TrotmanJudith, TaylorKerry, DalleStephane, StadlerRudolf, LisanoJulie, BunnVeronica, LittleMeredith, PrinceH Miles

C-ALCL treatment
MF treatment
Skin symptom improvement
Peripheral neuropathy

This study reports final data from the phase 3 ALCANZA trial, demonstrating significantly improved objective responses and progression-free survival with brentuximab vedotin compared to physician's choice in CD30-expressing mycosis fungoides (MF) or primary cutaneous anaplastic large-cell lymphoma (C-ALCL).

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

Modeling, Synthesis, and Biological Evaluation of Potential Retinoid-X-Receptor (RXR) Selective Agonists: Analogs of 4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahyro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene) and 6-(Ethyl(4-isobutoxy-3-isopropylphenyl)amino)nicotinic Acid (NEt-4IB).

Author: JurutkaPeter W, di MartinoOrsola, ReshiSabeeha, MallickSanchita, SabirZhela L, StaniszewskiLech J P, WardaAnkedo, MaiorellaEmma L, MinasianAni, DavidsonJesse, IbrahimSamir J, RabanSan, HaddadDena, KhamisiMadleen, SubanStephanie L, DawsonBradley J, CandiaRiley, ZillerJoseph W, LeeMing-Yue, LiuChang, LiuWei, MarshallPamela A, WelchJohn S, WagnerCarl E

Enhanced anti-proliferative potential
Improved RXR selectivity
Reduced cross-signaling

Novel analogs of NEt-4IB and bexarotene demonstrated improved RXR selectivity, reduced cross-signaling, and enhanced anti-proliferative potential in leukemia cells, suggesting their potential as more effective and safer therapeutic agents.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

3.

Combination of Sulindac and Bexarotene for Prevention of Intestinal Carcinogenesis in Familial Adenomatous Polyposis.

Author: BowenCharles M, WalterLewins, BorrasEster, WuWenhui, OzcanZuhal, ChangKyle, BommiPrashant V, TaggartMelissa W, ThirumurthiSelvi, LynchPatrick M, Reyes-UribeLaura, ScheetPaul A, SinhaKrishna M, VilarEduardo

Colorectal cancer prevention
FAP polyposis reduction

This study explores a novel chemopreventive regimen combining sulindac and bexarotene for familial adenomatous polyposis (FAP), a hereditary colorectal cancer syndrome. The study demonstrated a synergistic effect of the drug combination in reducing polyp development in mouse models and identified a potential serum biomarker for polyposis burden.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer.

Author: ThomasParijatham S, PatelAnisha B, LeeJ Jack, LiuDiane D, HernandezMike, MuzzioMiguel, ContrerasAlejandro, SepedaValerie, MaysCarrie, WeberDiane, VornikLana A, KhanSeema A, DimondEileen, Heckman-StoddardBrandy M, PerloffMarjorie, BrownPowel H

Breast cancer prevention

This phase I study evaluates topical bexarotene, a rexinoid with potential chemoprevention activity, for safety and toxicity in high-risk women for breast cancer.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

LKB1: An emerging therapeutic target for cardiovascular diseases.

Author: MolaeiAli, MolaeiEmad, SadeghniaHamidreza, HayesA Wallace, KarimiGholamreza

Cardioprotective effects
Heart disease prevention

This review article discusses the role of liver kinase B1 (LKB1) in cardiovascular disease. LKB1 is a protein that plays a role in energy metabolism and cell signaling. The researchers found that LKB1 protects the heart from damage and improves heart function.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

RXR Agonists Enhance Lenalidomide Anti-Myeloma Activity and T Cell Functions while Retaining Glucose-Lowering Effect.

Author: WuJian, WangXiaobei, ZhangMin, MathewsParker, KangYubin

Glucose lowering
Lipid lowering
Myeloma cell death
T cell function increase

Retinoid X receptor (RXR) agonists were investigated for their potential to enhance the anti-myeloma activity of lenalidomide. The study found that RXR agonists increased CRBN expression, killing myeloma cells and enhancing T-cell function.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

13.

Preventive and Therapeutic Effects of the Retinoid X Receptor Agonist Bexarotene on Tumors.

Author: QiLisi, GuoYuanyuan, ZhangPei, CaoXiaorong, LuanYuxia

Cancer treatment
Limited side effects

Bexarotene is a promising anti-cancer agent that selectively activates retinoid X receptors, showing therapeutic effects on various tumors. Clinical studies have demonstrated its favorable therapeutic profile with mild side effects, particularly in combination with other therapies.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

14.

Comparison of the Efficacy and Safety of Bexarotene and Photo(Chemo)Therapy Combination Therapy and Bexarotene Monotherapy for Cutaneous T-Cell Lymphoma.

Author: MoritaAkimichi, TateishiChiharu, IkumiKyoko, HayashiDaisuke, NakadaAya, NishiharaHaruna, ToriiKan, NishidaEmi, TsurutaDaisuke

CTCL treatment efficacy
Safety

This study compared the efficacy and safety of bexarotene and photo(chemo)therapy combination therapy with bexarotene monotherapy in Japanese patients with cutaneous T-cell lymphoma (CTCL).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

17.

Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells.

Author: XiaLiqun, ShenDanyang, ZhangYouyun, LuJieyang, WangMingchao, WangHuan, ChenYuanlei, XueDingwei, XieDajiang, LiGonghui

Cushing's disease treatment

Bexarotene, identified as an antagonist of Testicular receptor 4 (TR4), suppressed ACTH-secreting tumor growth, adrenal enlargement, and the secretion of ACTH and corticosterone in mice with Cushing's disease. This suggests bexarotene could be a potential novel therapeutic drug to treat Cushing's disease.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Teratogenicity and Fetal-Transfer Assessment of the Retinoid X Receptor Agonist Bexarotene.

Author: TakamuraYuta, KatoIzumi, Fujita-TakahashiManami, Azuma-NishiiMidori, WatanabeMasaki, NozakiRui, AkehiMasaru, SasakiTakanori, HiranoHiroyuki, KakutaHiroki

Cutaneous T-cell lymphoma treatment
Bone dysplasia
Fetal atrophy

Bexarotene, a retinoid X receptor (RXR) agonist used to treat cutaneous T-cell lymphoma, has been shown to cause fetal atrophy and bone dysplasia in rats. While fetal transfer of bexarotene was not detected by PET imaging, it was confirmed by using a gamma counter.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

[Effects and related mechanism of retinoid X receptor agonist bexarotene on atherosclerosis progression in diabetic apoE(-/-) mice].

Author: ZhuJiang, XuChangsheng, NingRuobing, ChaiDajun, LinJinxiu

Attenuated atherosclerosis
Improved lipid metabolism

A study of 46 apolipoprotein E knockout (apoE(-/-)) mice found that bexarotene treatment could attenuate arteriosclerosis progression in streptozotocin (STZ) induced diabetic apoE(-/-) mice. The mechanism might be related to suppressing oxidative stress, decreasing blood glucose levels, and improving lipid metabolism.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : Chinese

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