Abstract: This disclosure relates to dosage regimens for targeted TGF-? inhibition with a bi-functional fusion protein for use in a method of treating biliary tract cancer or inhibiting biliary tract tumor growth in treatment naïve patients, or patients with locally advanced or metastatic BTC who have failed or are intolerant to first-line systemic chemotherapy.

Abstract: The present disclosure relates generally to methods for treating a patient diagnosed with triple negative breast cancer (TNBC), involving identifying a patient likely to respond to treatment via targeted TGF-? inhibition with an anti-TGF? agent, and treating the subject with the anti-TGF? agent.

Abstract: This disclosure relates generally to dosage regimens for targeted TGF-? inhibition with a bi-functional fusion protein for use in a method of treating a treatment naïve patient diagnosed with stage III non-small cell lung cancer (NSCLC), and/or mitigating a pathological condition associated with chemotherapy and radiotherapy (cCRT).

Abstract: This disclosure relates generally to methods for treating a subject diagnosed with advanced non-small-cell lung cancer (NSCLC), involving targeted TGF-? inhibition with a bi-functional fusion protein, in combination with administration of systemic chemotherapeutic agents, wherein the combination of the bi-functional fusion protein of the present disclosure with systemic chemotherapeutic agents enhances anticancer efficacy over systemic chemotherapeutic agents alone.

Abstract: This disclosure relates to dosage regimens for targeted TGF-? inhibition with a bi-functional fusion protein for use in a method of treating cancer or inhibiting tumor growth in treatment naïve patients.

Abstract: This disclosure relates generally to body weight independent (BW-independent) dosing regimens and dosage forms of a bifunctional protein targeting human protein Programmed Death Ligand 1 (PD-L1) and Transforming Growth Factor ? (TGF?).

Abstract: This invention is in the field of pharmaceutical agents and specifically relates to compounds, compositions, uses and methods for treating cancer, by combining VEGF(R) inhibitors and inhibitors of HGF/SF:c-Met.

Abstract: This invention is in the field of pharmaceutical agents and specifically relates to compounds, compositions, uses and methods for treating cancer, by—combining VEGF(R) inhibitors and inhibitors of HGF/SF:c-Met.

Abstract: The present invention relates to new methods of modifying drug clearance and avoiding multi-drug resistance by modifying SXR activity. SXR is a transcriptional activator of MDR1, cytochrome P40-3A4 and cytochrome P40 2C8. SXR activation can significantly increase the metabolic inactivation and efflux of a wide range of chemotherapeutic agents, for example taxanes. Reducing and/or preventing SXR activation therefore diminishes drug resistance and drug clearance and forms the basis of important therapeutic methods which increase the performance of drugs, such as taxanes. Screening and drug identification methods are described which can identify drugs which are not susceptible to SXR related inactivation and increased efflux. In addition, drugs which can reduce these effects for other agents are provided.

Abstract: Methods for modulating the activity of the mammalian BAR/FXR receptor. The methods include methods of treating a hypocholesterolemic mammal comprising contacting the mammal with synthetic compounds able to modulate an activity characteristic of the BAR/FXR receptor. Other methods include a method of treating colon cancer in a mammal comprising administering a compound having a BAR/FXR antagonistic activity.

Abstract: The present invention provides methods for preventing or treating disorders associated with the degradation of cholesterol and bile alcohols through the use of ligands that interact with pregnane X receptors (PXR). In a preferred embodiment, PXR agonists are used to treat disorders associated with sterol 27-hydroxylase (CYP27) deficiency or mutation. The disorders associated with CYP27 deficiency include but not limited to cerebrotendinous xanthomatosis, cataracts, gallstone, tendon xanthomas, atherosclerosis, hepatomegaly, hypertriglyceridemia, and neurological and neuropsychiatric abnormalities such as peripheral neuropathy and dementia. In another preferred embodiment, PXR agonists are used to prevent or treat disorders that can be alleviated by enhancing the degradation of cholesterol or bile alcohols.

Abstract: Methods for modulating the activity of the mammalian BAR/FXR receptor. The methods include methods of treating a hypocholesterolemic mammal comprising contacting the mammal with synthetic compounds able to modulate an activity characteristic of the BAR/FXR receptor. Other methods include a method of treating colon cancer in a mammal comprising administering a compound having a BAR/FXR antagonistic activity.

Abstract: ET-743 is a small molecular weight compound with antineoplastic activity that inhibits the ability of the nuclear receptor SXR to trans activate gene transcription from SXR regulated response elements. The nuclear receptor SXR has been identified as a receptor that activates transcription of the mdr1 gene and thus increases multidrug resistance in cells. The interaction of SXR with the mdr1 gene and ET-743 provide a set of physiological mechanisms which can be exploited to identify novel inhibitors of SXR activation and mdr1 gene transcription and thus novel agents which exhibit an antineoplastic effect against tumor cells either alone or when coadministered with another antineoplastic agent.

Abstract: The orphan nuclear receptor SXR coordinately regulates drug clearance in response to a wide variety of xenobiotic compounds. The disclosure demonstrates that an HIV protease inhibitor binds SXR and activates its target genes. SXR ligands activate expression of MRP2, a critical regulator of bile flow and biliary drug excretion. Therefore, SXR binding compounds can be used for regulating drug clearance and treatment of hepatic disorders associated with impaired bile flow. The present invention relates to new methods of modifying drug clearance and avoiding multi-drug resistance by modifying SXR activity. SXR is a transcriptional activator of MDR1, cytochrome P40-3A4 and cytochrome P40 2C8. SXR activation can significantly increase the metabolic inactivation and efflux of a wide range of chemotherapeutic agents, for example taxanes.

Abstract: The present invention relates to new methods of modifying drug clearance and avoiding multi-drug resistance by modifying SXR activity. SXR is a transcriptional activator of MDR1, cytochrome P40-3A4 and cytochrome P40 2C8. SXR activation can significantly increase the metabolic inactivation and efflux of a wide range of chemotherapeutic agents, for example taxanes. Reducing and/or preventing SXR activation therefore diminishes drug resistance and drug clearance and forms the basis of important therapeutic methods which increase the performance of drugs, such as taxanes. Screening and drug identification methods are described which can identify drugs which are not susceptible to SXR related inactivation and increased efflux. In addition, drugs which can reduce these effects for other agents are provided.