flutamide

Ovarian cancer cell migration was inhibited upon introducing miR-449a and miR-449b-5p mimics. Together, our study suggests a novel dual-inhibitory mechanism of flutamide on the AR pathway (AR expression suppression in addition to direct androgen antagonism) and supports its chemopreventive potential in ovarian cancer, especially for HR patients with low miR-449 expression.

P1, N=24, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2028 --> Dec 2024 | Trial primary completion date: Dec 2025 --> Sep 2024

P2, N=54, Not yet recruiting, Zhejiang Provincial People's Hospital

Androgen receptor (AR) facilitates HCC cell growth, which was augmented by androgen (dihydrotestosterone [DHT]) and attenuated by anti-androgen (flutamide)...Conclusively, AR promotes HCC at least partially via upregulating BIRC7, IGFBP3, and NTSR1, which is enhanced by androgen and HBx. BIRC7 and NTSR1 facilitate HCC progression in a male-predominant manner.

P2/3, N=612, Active, not recruiting, NRG Oncology | N=175 --> 612 | Trial completion date: May 2031 --> May 2026

P3, N=800, Completed, Trans Tasman Radiation Oncology Group (TROG) | Active, not recruiting --> Completed

P1, N=24, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting

P4, N=62, Completed, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> May 2024 | Trial primary completion date: Dec 2025 --> May 2024

Our histological investigation further demonstrated sophorin's hepatoprotective function by restoring the typical histology of the liver. Based on the aforementioned information, we are able to come to the conclusion that sophorin supplementation might benefit wistar rats with flutamide-induced hepatic damage by reducing oxidative stress and hepatocellular inflammation.

Here, we demonstrate that AR is highly expressed in DSRCT relative to other fusion-driven sarcomas and that the AR antagonists enzalutamide and flutamide reduce DSRCT growth. Further, we find that AR antagonists reduce DSRCT growth in cells depleted of AR, establishing an AR-independent mechanism of action. These findings suggest that AR dependence is not the reason for male predominance in DSRCT and that AR-targeted therapies may provide therapeutic benefit primarily through an AR-independent mechanism that requires further elucidation.

P4, N=62, Active, not recruiting, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

In the DELC study, the safety of enzalutamide was comparable to that in previous reports. Serum levels of neuron-specific enolase and interleukin-6 were suggested as prognostic factors for castration-resistant prostate cancer with potential clinical utility.

P4, N=228, Recruiting, University of Colorado, Denver | Not yet recruiting --> Recruiting

Analysis of the human prostate cancer samples revealed similar results in a population with high expressions of the stem cell markers Oct4 and ABCB1A1. Our findings suggest that the adaptation of prostate cancer cells to antiandrogens could induce reprogramming into stem cells that survive in a low phosphocholine metabolism and cell cycle arrest and display drug resistance.

PCDH1 is a key prognostic biomarker and promoter of PAAD metastasis. Additionally, flutamide may serve as a novel compound that down-regulates PCDH1 expression as a potential treatment for combating PAAD progression and metastasis.

Ganoderma lucidum polysaccharide synergistically increased the effect of Docetaxel and Flutamide and increased the sensitivity of the prostate cancer cell lines to these drugs. Therefore, it may provide a new therapeutic strategy against prostate cancer.

P1, N=72, Active, not recruiting, University of Virginia | Trial completion date: Aug 2023 --> Aug 2024 | Trial primary completion date: May 2023 --> May 2024

Concerning OS, ADT + abiraterone, ADT + abiraterone + docetaxel, ADT + apalutamide, ADT + bicalutamide, ADT + darolutamide + docetaxel, ADT + enzalutamide, ADT + orteronel, and ADT + rezvilutamide were more effective than the standard of care (SOC). Comparing PFS, most treatments were more effective than SOC, excluding ADT + bicalutamide, nilutamide, flutamide, ADT + bicalutamide + palbociclib, and ADT + nilutamide...Novel oral chemotherapeutic agent combination therapies must replace current ADT monotherapy and ADT + docetaxel SOC. Even so, ADT + docetaxel with ARTA triplet therapy still is not the best mHSPC treatment and requires further study.

Based on the current limited evidence, Flutamide has a limited role in JNA management and further research is required. Its utilization should only follow discussion with the patient, their families, and within the multidisciplinary team.

P4, N=228, Not yet recruiting, University of Colorado, Denver | Initiation date: Jul 2023 --> Oct 2023

For example, flutamide, used to treat prostate cancer, inhibits hepatitis C virus proliferation by acting as an AhR antagonist, and methylated-pelargonidin, an AhR agonist, suppresses pro-inflammatory cytokine production...Furthermore, a preliminary structure-activity relationship study using sulochrin derivatives was performed. Our findings suggest the use of methylsulochrin derivatives as anti-HCV compounds with anti-inflammatory activity.

The combination of flutamide+PROSTVAC did not improve outcomes in men with nmCRPC compared with flutamide alone. (ClinicalTrials.gov Identifier: NCT00450463).

The 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay showed that after 24 hrs of exposure to piperine (15 µmol/ml), cell viability fell to 50% compared to the standard drug flutamide (SDF) (51 µmol/ml) with a lower IC concentration...The complementary charge between AKT1 and piperine was emphasized in the transient ligand-protein binding interaction in molecular dynamic modeling over 100 ns, and stable hydrogen bond interaction between Lys268 and Ser205 amino acid residues of the active pocket was hypothesized. Overall, the findings from our in vitro and MD simulations provide insights into the mechanism of piperine targeting AKT1 and offer a possible candidate for future prostate cancer therapeutic development.Communicated by Ramaswamy H. Sarma.

P1, N=24, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Dec 2024 --> Dec 2025

We also tested bicalutamide, enzalutamide, apalutamide, and darolutamide for their ability to activate inflammasomes in differentiated THP-1 cells. These results suggested that the reactive metabolites of flutamide and bicalutamide can cause the release of DAMPs from hepatocytes and activate inflammasomes. Inflammasome activation may be an important step in the activation of the immune system by flutamide or bicalutamide, which in some patients, can cause immune-related adverse events.

Pca induction consisted on the sequential administration of flutamide, N-methyl-N-nitrosourea and testosterone propionate implants...Our data highlight the exercise-induced remodelling of peripheral lymphocyte subpopulations and lymphocyte infiltration in prostate tissue. Moreover, exercise training promotes the remodelling prostate signalome in this rat model of prostate carcinogenesis.

P4, N=228, Not yet recruiting, University of Colorado, Denver | Initiation date: Apr 2023 --> Jul 2023

P4, N=228, Not yet recruiting, University of Colorado, Denver

They also showed significantly lower uptakes in AR-negative cells, indicating interactions with the AR receptor. However, the binding affinities were considerably reduced by the coordination to Tc, and the complex that exhibited the best biological behavior did not show sufficient specificity towards AR-positive cells.

Reporter assays revealed that ArtC displayed AR antagonist activity, albeit weaker than an AR antagonist flutamide. In addition, ArtC potently sensitized the resistant cells to apalutamide by inducing apoptotic cell death due to mitochondrial dysfunction. These results suggest that the intake of Brazilian green propolis containing ArtC improves prostate cancer therapy.

Parallel cultures of VCaP, DuCaP, PC346C, and LAPC4 were established in their respective culture media with steroid-stripped fetal calf serum (FCS) [dextran-coated charcoal-stripped FCS (DCC)] without androgen (ADT) or in DCC plus 1 μM of the ARTAs bicalutamide, OH-flutamide, or RD162 (an enzalutamide/apalutamide analog). Although the resistant phenotype is pluriform between models, it seems consistent within models, regardless of type of ARTA. These data suggest that the progression to and the phenotype of the CRPC state might already be determined early in carcinogenesis.

These data provide novel evidence for direct effects of FSH on prostate size and gene expression in chemically castrated mice. However, in chemically castrated men, FSH had no effect on PSA production. Whether FSH effects on prostate in humans also requires suppression of the residual adrenal-derived androgens and/or a longer period of rFSH stimulation, remains to be explored.

Finally, we found that four drugs (including vorinostat, fludroxycortide, oxolinic acid, and flutamide) might be effective and efficient in alleviating or reversing the status of severe hypoxia and poor infiltration of immune cells. Our constructed prognostic model, based on hypoxia-immune-related genes, has excellent effectiveness and clinical application value. Moreover, some small-molecule drugs are screened to alleviate severe hypoxia and poor infiltration of immune cells.

P3, N=2478, Recruiting, NRG Oncology | Suspended --> Recruiting | Trial completion date: Dec 2038 --> Dec 2033

The combination therapy with ATO and flutamide has augmented the anti-tumor effect on LNCaP and PC3 cells, which probably originates from their potential to induce apoptosis and inhibit the proliferation of PCa cells simultaneously.

The cytostatic activity of Oxy was also compared with that of the reference cytostatic drugs used in chemotherapy protocols, namely carboplatin, cisplatin, doxorubicin, epirubicin, etoposide, flutamide, 5-fluorouracil, irinotecan, oxaliplatin and sorafenib. The results obtained allow concluding that Oxy can be a promising anticancer agent to be used in chemotherapy protocols. Furthermore, its ability to inhibit crucial components of DDR can also be useful for the monotherapy or for combination with chemo and/or radiotherapy of cancer.

To determine if androgen-mediated PD-L1 downregulation was AR-dependent, we treated cells with flutamide, a selective AR antagonist, and prior to DHT treatment to pharmacologically inhibit AR-induced signaling...Investigation into the AR binding sites showed AR activation impacts NF-kB signaling by increasing IkBα and by possibly preventing NF-kB translocation into the nucleus, reducing PD-L1 promoter activation. This study provides evidence of sex-hormone mediated regulation of immune checkpoint molecules in vitro with potential ramification for immunotherapies.

Early efforts to augment ADT by adding adrenal-targeting agents (aminoglutethimide, ketoconazole) or AR antagonists (flutamide, bicalutamide, nilutamide, cyproterone) failed to achieve overall survival (OS) benefits, although they did exhibit some evidence of limited clinical activity...Specifically, the CYP17 inhibitor abiraterone acetate and the 2nd generation AR antagonists (enzalutamide, apalutamide and darolutamide) achieved OS benefits for PC patients, confirmed the importance of reactivated AR signaling in castration-resistant PC and validated important concepts that had been proposed in the field several decades ago but had remained so far unproven, including adrenal-targeted therapy and combined androgen blockade...Now the question is raised whether we have accomplished the maximum AR axis inhibition possible or there is still room for improvement. This review, marking the 80-year anniversary of ADT and 10-year anniversary of successful ARSIs, examines their current clinical use and discusses future directions, in particular combination regimens, to maximize their efficacy, delay emergence of resistance and improve patient outcomes.

The therapeutic action of nitroaromatic antiandrogens nilutamide and flutamide may be complicated by their cytotoxicity, whose mechanisms are still incomprehensively understood. Using murine hepatoma MH22a cells, the obtained cytotoxicity vs. E correlation based on the data of model nitroaromatic compounds shows that redox cycling and oxidative stress could be the main factor of cytotoxicity of nitroaromatic antiandrogens. Other minor cytotoxicity factors could be their redox metabolism involving NAD(P)H:quinone oxidoreductase (NQO1) and cytochromes P-450.

Among all the compounds 8 L, 8q, 9n and 9p showed higher inhibitory activity on the viability of HL 60 than the standard methotrexate...TNFα and Leptin as compared to the standard suramin, while 9p has activity comparable to suramin against IGF1, VEGF, FGFb, and Leptin...Additionally, we present in silico molecular docking data to provide the structural rationale of observed TNFα inhibition against newly synthesized compounds. Overall, the synthesized flutamide derivatives have not only anticancer activity, but also possess dual inhibitory effect (anti-angiogenesis and antioxidant) and hence can act as a promising avenue to develop further anticancer agents.