- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Journal: Nuclear Receptors Are Differentially Expressed and Activated in KAIMRC1 Compared to MCF7 and MDA-MB231 Breast Cancer Cells. (Pubmed Central) - Nov 22, 2019
The signal of the PPARE reporter increased in a dose-dependent manner with rosiglitazone (PPARg agonist) in KAIMRC1, MCF7, and MDA-MB231 when the proliferator-activated receptors gamma (PPARg)/RXRa receptors were cotransfected...In the three cell lines, Bexarotene-induced retinoid X receptor response element (RXRE)-luciferase reporter activation was induced only if the RXRa/LXRa heterodimer were co-expressed...In conclusion, we showed that nuclear receptors are differentially expressed, activated and also their ligand produced distinct effects in KAIMRC1 compared to MCF7 and MDA-MB231. This finding gives us confidence that KAIMRC1 has a unique biological phenotype.
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Preclinical, Journal: RXRα Nitro-ligand Z-10 and Its Optimized Derivative Z-36 Reduce β-amyloid Plaques in AD Mouse Model. (Pubmed Central) - Nov 21, 2019
Bexarotene, an agonist of retinoid X receptor alpha (RXRα), has been shown to increase the expression of apoE, ABCA1, and ABCG1 by activating RXR/LXR and RXR/PPAR heterodimers, resulting in amyloid β (Aβ)-protein clearance in the brain of an Alzheimer's disease (AD) mouse model and reversal of mouse cognitive deficits...This may due to the stronger ability of Z-36 than Z-10 in activating RXR/LXR and RXR/PPAR heterodimers and inducing ABCA1 and ABCG1 expressions. Thus, the 2- rather than 4- position was the better site for Z-10 modification as to RXRα transactivation, and Z-36 is an optimized derivative of Z-10 as to reducing Aβ plaques in AD mouse model.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Preclinical, Journal, PD(L)-1 Biomarker, IO Biomarker: Retinoid X receptor agonist LG100268 modulates the immune microenvironment in preclinical breast cancer models. (Pubmed Central) - Nov 9, 2019
Bexarotene is the only rexinoid approved by the FDA for the treatment of refractory cutaneous T-cell lymphoma...In the MMTV-PyMT murine model of triple negative breast cancer, LG268 treatment of established tumors prolonged survival, and in combination with anti-PD-L1 antibodies, significantly (p = 0.05) increased the infiltration of cytotoxic CD8 T cells and apoptosis. Collectively, these data suggest that the use of LG268, a RXR agonist, can improve response to immune checkpoint blockade in HER2+ or triple-negative breast cancer.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Endogenous Retinoid X Receptor Ligands Act As Tumor Suppressors in MLL-AF9 Mouse Leukemia (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_3853;
Finally, we observed a significant dose-dependent effect of combination ATRA and bexarotene treatment in in vivo in MLL-AF9 leukemic mice with a striking reduction in the tumor burden of treated mice compared to the control cohort . These data provide a strategy for clinical retinoid therapies in leukemias beyond acute promyelocytic leukemia and provide a mechanism for integrating retinoid therapy into future clinical trials.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Journal: Bexarotene - a novel modulator of AURKA and the primary cilium in VHL-deficient cells. (Pubmed Central) - Oct 31, 2019
Importantly, the inability of an alternate retinoid X receptor (RXR) agonist to rescue ciliogenesis, in contrast to bexarotene, suggested the existence of multiple bexarotene driven mechanisms. We found that bexarotene decreased AURKA expression in VHL-deficient cells, thereby restoring the ability of these cells to ciliate in the absence of VHL Finally, bexarotene treatment reduced the propensity of subcutaneous lesions to develop into tumors in a mouse xenograft model of RCC, with a concomitant decrease in activated AURKA, highlighting the potential of bexarotene as an intervention strategy in the clinic to manage renal cystogenesis associated with VHL-deficiency and elevated AURKA expression.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Journal: Scaffold-Hopping from Synthetic Drugs by Holistic Molecular Representation. (Pubmed Central) - Oct 29, 2019
WHALES descriptors identified four agonists with innovative molecular scaffolds, populating uncharted regions of the chemical space. One of the agonists, possessing a rare non-acidic chemotype, revealed high selectivity on 12 nuclear receptors and comparable efficacy as bexarotene on induction of ATP-binding cassette transporter A1, angiopoietin like protein 4 and apolipoprotein E. The outcome of this research supports WHALES as an innovative tool to explore novel regions of the chemical space and to detect novel bioactive chemotypes by straightforward similarity searching.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Journal: Lipophilic activated ester prodrug approach for drug delivery to the intestinal lymphatic system. (Pubmed Central) - Oct 24, 2019
We now report a study in which a lipophilic prodrug approach was used to efficiently deliver bexarotene (BEX) and retinoic acid (RA) to the intestinal lymphatic system using activated ester prodrugs...Synergism between BEX and RA was also demonstrated in vitro by cell growth inhibition assays using lymphoma cell lines. In conclusion, the activated ester prodrug approach results in efficient delivery of drugs to the intestinal lymphatic system, which could benefit patients affected by a large number of pathological conditions.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Clinical, Journal: Cutaneous lymphomas : Clinical presentation - diagnosis - treatment (Pubmed Central) - Oct 11, 2019
While the rare CD4-positive lymphoproliferation and acral CD8-positive lymphoma present with an invariably indolent course, cutaneous peripheral T‑cell lymphomas exhibit an aggressive clinical behavior. Among the subgroup of cutaneous B‑cell lymphomas, primary cutaneous marginal zone lymphoma and follicle center cell lymphoma belong to indolent entities with almost unrestricted overall survival, whereas cutaneous large B‑cell lymphoma presents with a significant risk of systemic dissemination and is associated with high lethality.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Journal: Synergistic effect of a retinoid X receptor-selective ligand bexarotene and docetaxel in prostate cancer. (Pubmed Central) - Oct 3, 2019
When mitotic slippage happens, BEX can synergistically strengthen the anti-proliferation of DTX in a way of significantly down-regulating cyclinB1 and CDK1 expression, and then arresting cells in G2 phase. Results from this study showed that BEX-induced G2 arrest and DTX-induced mitotic arrest probably contributed to the synergistic effect of BEX and DTX.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Clinical, Journal: Association of APOA5 and APOC3 Genetic Polymorphisms With Severity of Hypertriglyceridemia in Patients With Cutaneous T-Cell Lymphoma Treated With Bexarotene. (Pubmed Central) - Sep 28, 2019
After bexarotene treatment, carriers of at least 1 of the 2 minor alleles of APOA5 c.-1131T>C and APOC3 c.*40C>G showed lower levels of triglycerides than noncarriers (mean [SD], 241.59 [169.91] vs 330.97 [169.03] mg/dL, respectively; P = .02). These results indicate that the screening of APOA5 and APOC3 genotypes may be useful to estimate changes in triglyceride concentrations during bexarotene treatment in patients with CTCL and also to identify the best candidates for bexarotene therapy based on the expected adverse effect profile.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Clinical, FDA event, Journal: Identification of FDA-approved oncology drugs with selective potency in high-risk childhood ependymoma. (Pubmed Central) - Sep 7, 2019
Axitinib's anti-tumor mechanism in ependymoma cell lines involved inhibition of PDGFR-alpha and PDGFR-beta and was associated with reduced mitosis-related gene expression and cellular senescence. The clinically available, ependymoma -selective oncology drugs identified by our study have the potential to critically inform design of upcoming clinical studies in ependymoma, in particular for those children with recurrent ependymoma who are in the greatest need of novel therapeutic approaches.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Journal: Therapeutic modulation of retinoid X receptors - SAR and therapeutic potential of RXR ligands and recent patents. (Pubmed Central) - Sep 5, 2019
Expert opinion: While the use of RXR modulators has been claimed in several novel and promising indications, little progress has been made in the development of innovative rexinoids with improved (subtype-)selectivity. Next-generation RXR modulators that selectively target the RXR subtypes for individual indications may be required to exhaustively exploit the therapeutic potential of RXRs.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Clinical, Journal: Treatment of Rosai-Dorfman Disease with oral Bexarotene: a case series. (Pubmed Central) - Aug 8, 2019
There is no specific treatment for RDD, and multiple therapeutic approaches have been described with variable success rates. This is the first report of the use of oral bexarotene as an effective and safe treatment for RDD.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Preclinical, Journal: Optimized bexarotene aerosol formulation inhibits major subtypes of lung cancer in mice. (Pubmed Central) - Aug 3, 2019
For the first time, our studies demonstrate a new, clinically relevant aerosolized bexarotene formulation that exhibits preventive efficacy in major subtypes of lung cancer. This approach would be a major advance in preventing lung cancer incidence in persons at high risk of lung cancer e.g., former or present smokers.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Clinical, Journal: Primary cutaneous lymphoma-a case series of 163 patients (Pubmed Central) - Jul 26, 2019
This registry describes frequent findings and shows rare variants. You can only diagnose what you know; accordingly, a collection of case reports, which we wish to encourage, can help in processing and specification of entities.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Journal: Association between Alzheimer's disease and cancer - a short overview. (Pubmed Central) - Jul 25, 2019
Recently, new therapeutic strategies have also been proposed against these diseases, as we are studying common onset mechanisms in neurodegenerative diseases such as AD and cancer. Above all, at this time the use of - Nilotinib - a tyrosine kinase inhibitor, protein kinase C and anti-cancer drug bexarotene would be the most promising drugs as far as investigated.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Biomarker, Preclinical, Journal: Pharmacometabolomic Pathway Response of Effective Anticancer Agents on Different Diets in Rats with Induced Mammary Tumors. (Pubmed Central) - Jul 25, 2019
Diet may change the chemopreventive efficacy of given agents due to the altered physiological status of the subject. Here, metabolomics response to a chemopreventive agent targretin or tamoxifen, in rats with methylnitrosourea-induced tumors on a standard diet (4% fat, CD) or a high fat diet (21% fat, HFD) was evaluated, and found that (1) the metabolome was substantially affected by diet and/or drug treatment; (2) multiple metabolites were identified as potential pharmacodynamic biomarkers related to targretin or tamoxifen regardless of diet and time; and (3) the primary bile acid pathway was significantly affected by targretin treatment in rats on both diets, and the lysolipid pathway was significantly affected by tamoxifen treatment in rats on the high fat diet.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Review, Journal: Integrating novel systemic therapies for the treatment of mycosis fungoides and Sézary syndrome. (Pubmed Central) - Jun 22, 2019
Novel agents in advanced development include the monoclonal antibody IPH4102,duvelisib,and the new modified formulation of denileukin diftitox. The choice of agents for patients is typically a balance of patient factors (age, co-morbidities, geographic location), relative efficacy and toxicity.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Review, Journal: Systemic Treatment Options for Advanced-Stage Mycosis Fungoides and Sézary Syndrome. (Pubmed Central) - Jun 15, 2019
International consensus guidelines are available; however, the lack of comparative trials means that there is no clear algorithmic approach to treatment. This review article reports on the systemic treatment options in current use for advanced CTCL, and on the possible future therapies, acknowledging that an algorithmic approach is not yet forthcoming to guide treatment prioritization.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Journal, Monotherapy: Retinoic Acid Receptor Agonist as Monotherapy for Early-Stage Mycosis Fungoides: Does it Work? (Pubmed Central) - Jun 15, 2019
This review article reports on the systemic treatment options in current use for advanced CTCL, and on the possible future therapies, acknowledging that an algorithmic approach is not yet forthcoming to guide treatment prioritization. Early-stage MF patients may benefit from low dose RAR-agonist monotherapy, although the CR rate is low.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor, Differin (adapalene) / Galderma Laboratories
Journal: Carboxylation of Aryl Triflates with CO Merging Palladium and Visible-Light-Photoredox Catalysts. (Pubmed Central) - Jun 13, 2019
Furthermore, a parallel decarboxylation-carboxylation reaction has been demonstrated in an H-type closed vessel that is an interesting concept for the strategic sector. Spectroscopic and spectroelectrochemical studies indicated electron transfer from the Ir(III)/DIPEA combination to generate aryl carboxylate and Pd(0) for catalytic turnover.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Journal: Discovering alkylamide derivatives of bexarotene as new therapeutic agents against triple-negative breast cancer. (Pubmed Central) - May 31, 2019
Furthermore, the bexarotene derivatives also showed significant effects in inhibiting TNBC cell proliferation and migration, modulating cancer stem cell markers expressions, as well as limiting the epithelial-mesenchymal transition (EMT) activities of TNBC cell lines in terms of downregulating EMT marker and blocking nuclear translocation of β-catenin. Therefore, we propose the alkylamide derivatives of bexarotene as potential candidates for novel anticancer therapeutics against TNBC.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Trial completion: Phase II Study of Bexarotene in Patients With Acute Myeloid Leukemia (clinicaltrials.gov) - Apr 20, 2019
P2, N=25, Completed,
Therefore, we propose the alkylamide derivatives of bexarotene as potential candidates for novel anticancer therapeutics against TNBC. Active, not recruiting --> Completed
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Retrospective data, Journal: Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium. (Pubmed Central) - May 31, 2018
However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Journal: Oral bexarotene for post-transplant cutaneous T-cell lymphoma. (Pubmed Central) - May 30, 2018
Our report is the second to describe PT-CTCL demonstrating a long-term complete response to oral bexarotene. Given its anti-carcinogenic properties and favorable toxicity profile, oral bexarotene represents an appealing treatment option for PT-CTCL refractory to skin-directed therapies.
- |||||||||| Targretin oral (bexarotene oral) / ReXceptor
Trial completion, Enrollment change, Trial completion date, Trial initiation date, Trial primary completion date, Combination therapy, Metastases: BATTLE Program: Tarceva and Targretin in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - Mar 1, 2018
P2, N=37, Completed,
Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene. Active, not recruiting --> Completed | N=72 --> 37 | Trial primary completion date: Nov 2019 --> Feb 2018 | Trial completion date: Nov 2020 --> Feb 2018 | Initiation date: Nov 2006 --> Nov 2006
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