72 results about "Castration Resistance" patented technology

This invention relates to talazoparib, or a pharmaceutically acceptable salt thereof, in combination with enzalutamide, or a pharmaceutically acceptable salt thereof, for the treatment of homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer and methods of increasing overall survival thereof.

Methods and compositions for treatment of prostate cancers, such as androgen receptor (AR) deficient and androgen receptor (AR) low cancers, are disclosed. The methods include administration of an agent that inhibits activity of eIF4F or an agent that disrupts the eIF4F translation-initiation complex (composed of eIF4E, eIF4A, and eIF4G).

The invention provides a dalotamide monophosphate compound shown as a formula I or a pharmaceutically acceptable salt thereof, and n is an integer of 1-3, preferably an integer of 1-2. The compound provided by the invention can be used for preparing medicines for treating adult patients with non-metastatic castration-resistant prostate cancer with high metastasis risk.

The present disclosure provides methods for treating prostate cancer or metastatic castration-resistant prostate cancer, reducing the severity of prostate cancer or metastatic castration-resistant prostate cancer, or inhibiting the growth of prostate cancer or metastatic castration-resistant prostate cancer. The methods of the present disclosure comprise administering to a subject in need thereof a therapeutically effective amount of a bispecific antibody, or antigen-binding fragment thereof, that specifically binds to prostate specific membrane antigen (PSMA) and CD28, as a monotherapy or in combination with an anti-PD1 antibody.

The invention belongs to the technical field of cancer treatment, and discloses a method for inhibiting castration-resistant prostate cancer proliferation and metastasis by promoting collagen degradation through targeting ADAMTS1. According to the method, ADAMTS1 is determined to be a mechanism key point for linking epigenetic reprogramming with biomechanical microenvironment destruction. The ADAMTS1 is reactivated to degrade a collagen-rich matrix, the FAK / MAPK mechanical transduction signaling pathway is inhibited, and the epithelial-mesenchymal transition (EMT) is reversed. The strategy not only achieves more than 90% of tumor inhibition effect, but also exhausts immunosuppressive macrophages and regulatory T cells to reverse immunosuppression by enhancing toxic CD8 + T cell infiltration. The research determines that epigenetic-ECM coevolution is a symbolic feature of CRPC, and provides a reasonably designed combination therapy for treating castration-resistant prostate cancer.

Methods of treating non-metastatic castration-resistant prostate cancer in a subject having severe liver damage are provided.SOLUTION: Provided are methods of treating non-metastatic castration-resistant prostate cancer in a subject with severe hepatic impairment with an androgen receptor inhibitor comprising 4 - [7 - (6-cyano-5-trifluoromethylpyridin-3-yl) - 8-oxo-6-thioxo-5, 7-diazaspiro [3.4] oct-5-yl] - 2-fluoro-N-methylbenzamide (apalutamide).SELECTED DRAWING: None

The present invention relates to a composition for the treatment of castration resistant prostate cancer, the composition comprising (i) a first active ingredient comprising a CDK9 degrading agent; and (ii) a second active ingredient, wherein the second active ingredient comprises olaparib. The effects of inhibiting tumor cell proliferation and promoting cell apoptosis of the composition are obviously higher than those of a single drug under the same dosage.

This is a method for treating prostate cancer. Specifically, it involves the use of the compound shown in Formula I or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating metastatic castration-resistant prostate cancer. [Formula 1] JPEG2026521901000005.jpg32155

The present disclosure relates to niraparib and abiraterone acetate, plus prednisone or prednisolone; for use in a method of improving the efficacy of treatment of metastatic castration-resistant prostate cancer (mCRPC) in a patient with DNA-repair anomalies, in particular for improving the median radiographic progression-free survival (rPFS).

The invention relates to the technical field of biological medicine, and particularly discloses application of nefenavir. Nefinavir is used for preparing a medicine for treating or preventing castration-resistant prostate cancer, and the medicine can specifically up-regulate expression of DHCR7, induce DNA damage of tumor cells and activate a cell cycle arrest pathway mediated by periodic protein of the cells so as to inhibit key biological processes such as proliferation of the tumor cells, cholesterol metabolism and the like; especially, formation and amplification of multinuclear giant cells in castration-resistant prostate cancer can be effectively inhibited by up-regulating expression of DHCR7, so that malignant progression of multinuclear giant cell mediated tumors and treatment of drug resistance are blocked. Finally, the castration-resistant prostate cancer is prevented and treated, and the technical bottlenecks that an existing castration-resistant prostate cancer treatment means is limited in curative effect, and the drug resistance and metastasis capability mediated by multinuclear giant cells are difficult to inhibit in a targeted manner are solved.

The application belongs to the technical field of biological medicine, and discloses application of a MYLK3 gene inhibitor in preparation of a drug for treating castration-resistant prostate cancer. The biological function of MYLK3 in prostate cancer is confirmed for the first time, an intervention means with the gene as a target point is provided, and it is confirmed that the MYLK3 inhibitor can improve the sensitivity of castration-resistant prostate cancer to androgen receptor antagonists. A gene therapy drug with the human MYLK3 gene as a treatment target point is specially provided, which is suitable for the treatment of prostate cancer (especially castration-resistant prostate cancer), and can also be combined with other targeted drugs to improve the treatment effect. By designing a reasonable RNAi target sequence for the target gene, a retrovirus vector plasmid containing the target sequence is successfully constructed, which has a significant inhibitory effect on the proliferation ability of prostate cancer cells, and significantly increases the sensitivity of prostate cancer cells to AR antagonists.

This invention relates to talazoparib, or a pharmaceutically acceptable salt thereof, in combination with enzalutamide, or a pharmaceutically acceptable salt thereof, for the treatment of metastatic castration-resistant prostate cancer and methods of increasing survival thereof.

Described herein are methods of treating non-metastatic castrate-resistant prostate cancer using an approved drug product comprising apalutamide, enzalutamide or darolutamide. Also described here are drug products containing apalutamide enzalutamide or darolutamide, and methods of selling or offering for sale an anti-androgen drug product.

The present invention relates to methods for predicting the progression of prostate cancer, specifically metastatic castration-resistant prostate cancer (mCRPC), in an individual. The invention employs gene expression profiling combined with predictive modeling to assess the likelihood of overall survival and biochemical recurrence following treatment.

The present disclosure relates to methods of treating prostate cancer, including, for example, metastatic prostate cancer, castration-resistant prostate cancer, and metastatic castration-resistant prostate cancer, in a subject in need thereof wherein the method comprises administering to the subject a therapeutically effective amount of Compound A or a pharmaceutically acceptable salt thereof, and further comprising the step of stopping or reducing the administration of a CYP3A inhibitor or inducer, an efflux transporter substrate or inhibitor, or an uptake transporter substrate or inhibitor to the subject prior to commencing administration of Compound A or a pharmaceutically acceptable salt thereof.

The application discloses castration-resistant prostate cancer nucleic acid aptamer and a screening method and application thereof, the nucleotide sequence of the aptamer comprises a DNA fragment shown in any one of sequence 1 or sequence 2; the aptamer has the advantages of small molecular weight, low immunogenicity, high affinity and the like; in addition, the screening technology adopted by the nucleic acid aptamer is low in cost, can be mass-produced in vitro, is good in repeatability, and is easy to transport and preserve; and the nucleic acid aptamer can be combined with castration-resistant prostate cancer tissue cells with high affinity and high specificity. The nucleic acid aptamer can be used to early detect the castration-resistant state of prostate cancer from the cellular and molecular level, and has important significance for timely adjusting prostate cancer medication and improving prognosis.

This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a piperazine (or similar) structure which function as antagonists of androgen receptor activity, and their use as therapeutics for the treatment of cancer (e.g., castration-resistant prostate cancer) and other conditions characterized with androgen receptor activity and / or androgen receptor expression.

Small molecule allosteric modulators of androgen receptor are disclosed. The compounds may inhibit androgen receptor coactivator recruitment, such as by preventing formation of protein-protein interaction (PPI) complexes and / or disrupting PPI complexes. A method of treating prostate cancer, such as castration-resistant prostate cancer, includes administering a small molecule allosteric modulator of androgen receptor.

This document provides methods and materials for treating cancer (e.g., prostate cancer). For example, methods for using one or more agents that can regulate splicing of a nucleic acid (e.g., a precursor-messenger ribonucleic acid (pre-mRNA)) encoding one or more androgen receptor (AR) polypeptides to treat a mammal having prostate cancer (e.g., castration-resistant prostate cancer (CRPC)) are provided.

The present invention belongs to the technical field of biopharmaceuticals, and specifically relates to a tetrahydroquinoline NTD inhibitor and a use thereof. The present invention provides a novel NTD inhibitor, in which a bisphenol A moiety in EPI-002 is replaced with a tetrahydroquinoline structure, and rational drug design is carried out using this as a core scaffold, thereby enhancing the inhibitory activity of the compound against full-length AR and AR splice variants, while improving pharmacokinetic properties. The compound prepared in the present invention exhibits inhibitory effects toward the proliferation of castration-resistant prostate cancer cells and PSA luciferase activity, the effects thereof are superior to those of clinical drugs; it also possesses good oral bioavailability and plasma exposure.

The application discloses antisense oligonucleotides of METTL3 and application thereof in prostate cancer. It is found that inhibiting the expression level of METTL3 can reduce the proliferation of castration-resistant prostate cancer cells, and restore the drug sensitivity of drug-resistant prostate cancer cell strains, thereby providing a new means for treating castration-resistant prostate cancer and drug-resistant prostate cancer.

Downregulated miR-99b-5p and upregulated mTOR cooperatively promotes the African American (AA) PCa aggressiveness and drug resistance. Nuclear mTOR, AR, and SMARCD1 are highly expressed in AA PCa (MDA PCa 2b) compared to EA PCa (LNCaP) cell line. miR-99b-5p inhibited protein levels of mTOR, AR / AR-V7 and SMARCD1 in cytoplasm and nuclei of EA and AA PCa. miR-99b-5p effectively inhibits cell proliferation / survival and induced cell apoptosis in EA and AA PCa cells. Moreover, combination of miR-99b-5p and enzalutamide (Enz) synergistically enhances the cytotoxicity against aggressive AA PCa and castration resistant prostate cancer (CRPC). miR-99b-5p or miR-99b-5p / Enz significantly reduces the recruitment of mTOR to the genes involved in the metabolic reprogramming in CRPC. miR-99b-5p can function as an epigenomic driver to modulate the mTOR / AR / SMARCD1 signaling axis in AA PCa and resistant CRPC. miR-99b-5p can be utilized as a biomarker for identifying the presence of prostate cancer.

The invention belongs to the technical field of active compounds, and particularly relates to application of Nur77 to regulation of active components and an antitumor drug. In the process that metabolic reprogrammed solid tumors uptake nutrient substances through macropinocytosis in a nutrition-deficient microenvironment, the Nur77 regulates active ingredients, promotes specific binding of an LBD binding domain of the Nur77 and ATP6V1A, excessively activates macropinocytosis, inhibits expression of macropinocytosis-related signal channels such as mTOR and the like, destroys nutrition perception and metabolic homeostasis of tumor cells, and has the effect of inhibiting tumor cells. According to the present invention, with the application of the anti-tumor compound, the cell macrovesicular death can be triggered, the significant treatment effect can be provided for the metabolism reprogramming solid tumors such as castration-resistant prostate cancer at the low concentration, and the efficient anti-tumor strategy has advantages of clear target spot, controllable toxicity window and low drug resistance risk; therefore, the technical problem that existing active ingredients are difficult to specifically intervene in macropinocytosis is solved.

The invention discloses application of 19-hydroxybufalin in preparation of a medicine for treating prostatic cancer, and belongs to the technical field of pharmaceutical preparations. The 19-hydroxybufalin is found to be targeted in vivo and in vitro for the first time, and the growth of prostate tumors is remarkably inhibited, so that the survival basis of tumor cells is fundamentally weakened, programmed death of the tumor cells is triggered, and tumor regression is effectively induced; a brand-new treatment approach is provided, namely, a non-classical drug target, namely HELLS, is degraded in a targeted manner, so that a new treatment choice is expected to be provided for a patient lacking existing target mutation; the provided 19-hydroxybufalin can be used for treating advanced prostate cancer, especially castration-resistant prostate cancer, and a new candidate treatment drug with great potential and a brand new treatment strategy are provided for effectively solving the problem that chemotherapy drug resistance and targeted therapy selection are limited in the castration-resistant prostate cancer at present.

Herein is reported a class of chiral compounds with paradoxical effects on the androgen receptor (AR). The (R)-enantiomers behave like classical anti-androgens while the (S)-enantiomers activate AR signaling. In castration-resistant prostate cancer, the change during the course of therapy to growth in the presence of AR targeted therapeutics, a harbinger of progression to lethal disease, is commonly attributed to acquired mutations of the AR-ligand binding domain. This is the first report of an antagonist-agonist duality solely due to structural enantiomerism, without any modification to the AR binding site.

To provide a method for treating prostate cancer.SOLUTION: The present application relates to a method for treating and / or preventing prostate cancer, including metastatic and / or castrate-resistant prostate cancer, in a subject in need of treatment, comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, polymorph, isotopic derivative, or prodrug thereof.SELECTED DRAWING: Figure 5

Embodiments of the invention are directed to the treatment of subjects with prostate cancer, in particular those with castration resistant prostate cancer, with glucocorticoid receptor antagonists. The prostate cancer may be one that has become resistant to androgen deprivation therapy, for example, by increase in glucocorticoid receptor expression and / or activity.

The present disclosure discloses application of PRDX5 and GPX4 genes in preparation of drugs for castration-resistant prostate cancer and belongs to the technical field of biological medicines. The present disclosure proposes that silencing or interfering with the expression of the PRDX5 and / or GPX4 genes can be used in the treatment or adjuvant treatment of castration-resistant prostate cancer. The present disclosure proposes for the first time a new strategy for preparing the drugs for the treatment of CRPC using siRNA in combination with an androgen receptor antagonist. The pharmaceutical composition comprising siRNA in combination with an androgen receptor antagonist according to the present disclosure can be used for the treatment of castration-resistant prostate cancer and significantly improves the inhibitory effect of enzalutamide on castration-resistant prostate cancer, which provides the basis for the design and clinical application of nucleic acid drugs with important clinical therapeutic significance.