Abstract: The present invention provides a method of treatment of sarcoma comprising administering to a patient in need thereof a compound of general formula (I), in which R1, R2, R3, and R4, are as defined herein, alone or in pharmaceutical compositions or combinations comprising said compounds as a sole agent or in combination with other active ingredients.

Abstract: The present invention relates to compositions and methods for detecting CDK4/6 response and resistance.

Abstract: The present application relates to compounds comprising an ester, a thioester, or a hydrazide moiety and methods of synthesizing these compounds. The present application also relates to pharmaceutical compositions containing the compounds and methods of treating cell proliferative disorders mediated by the Hedgehog (Hh) signaling pathway, such as cancer, by administering the compounds and pharmaceutical compositions to subjects in need thereof.

Abstract: Described in exemplary embodiments herein are methods, compositions, and kits for diagnosing, prognosing, monitoring, treating and/or preventing a hemopoietic malignancy and/or relapse thereof in a subject. In some embodiments, the methods can include determining an average cellular mass of cells in a sample from the subject and/or detecting one or more molecular signatures in one or more of the cells. In some embodiments, treatment includes administering one or more BCR-ABL tyrosine kinase inhibitors or a pharmaceutical formulation thereof, one or more pre-BCR signaling pathway inhibitors or a pharmaceutical formulation thereof, one or more p38 MAPK inhibitors or a pharmaceutical formulation thereof; or any combination thereof.

Abstract: The present disclosure provides compounds of Formula (I?) (e.g., compounds of Formula (I)), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

Abstract: This disclosure features structurally-stabilized and/or cysteine-reactive peptide inhibitors for selective targeting of BFL-1, or dual targeting of BFL-1 and MCL-1. Also disclosed are methods of using such structurally-stabilized and cysteine-reactive peptides in the treatment of BFL-1- and/or MCL-1-expressing or -dependent cancers or diseases of cellular excess (e.g., autoimmune or inflammatory conditions). Also provided are combination therapies comprising such structurally-stabilized and/or cysteine-reactive peptides and inhibitors of the DNA damage response pathway, such as an ATM kinase inhibitor, ATR kinase inhibitor, CHK1/2 inhibitor, or PARP inhibitor; or an inhibitor of MCL-1, or a selective inhibitor of BCL-2, or an inhibitor of BCL-2/BCL-XL, for the treatment of BFL-1-expressing or -dependent cancers (e.g., AML), BFL-1 and MCL-1-expressing or -dependent cancers, or diseases of cellular excess (e.g., autoimmune or inflammatory conditions).

Abstract: The present invention relates to methods of determining a cancer treatment prognosis for a subject in need thereof by evaluating epigenetic and genetic changes within a tumor sample from the subject. The present invention further provides methods of treating cancer in a subject by evaluating epigenetic and genetic changes within a tumor sample from the subject. In addition, the present invention provides methods of screening test agents to identify agents that decrease tumor cell plasticity.

Abstract: Provided herein are compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the compounds or compositions disclosed herein for treating and/or preventing proliferative diseases, cancers, carcinoma lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, ovarian cancer, colon cancer, colorectal cancer, leukemia, sarcoma and/or cardiovascular diseases in a subject in need thereof. In certain embodiments, the sarcoma is Ewing's sarcoma. Provided are methods of inhibiting a histone demethylase in a subject and/or in a cell, tissue, or biological sample. In certain embodiments, the histone demethylase is a KDM. In certain embodiments, the KDM is KDM5. In certain embodiments the biological sample is a cell. In certain embodiments, the biological sample is a tissue.

Abstract: The present disclosure provides, in part, methods of discovering immunotherapy targets in vivo, therapeutic compositions (e.g., shRNA, immunoresponsive cells expressing shRNA and/or a chimeric antigen receptors (CAR)), and methods of use thereof.

Abstract: Antibody molecules that specifically bind to PD-1 are disclosed. The anti-PD-1 antibody molecules can be used to treat, prevent and/or diagnose cancerous or infectious conditions and disorders.

Abstract: The present invention relates to novel compounds which are able to modulate b-raf kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.

Abstract: The present application provides bifunctional compounds of Formula (Ia) or (Ib): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 8 (CDK8). The present application also relates to methods for the targeted degradation of CDK8 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK8 which can be utilized in the treatment of disorders modulated by CDK8.

Abstract: The present invention is based, in part, on the identification of biomarkers, and methods of modulate thereof, for sensitizing cancer cells to T cell-mediated killing. For example, the present invention, in part, comprises methods of sensitizing cancer cells in a subject afflicted with a cancer to cytotoxic T cell-mediated killing comprising administering to a subject a therapeutically effective amount of an agent that modulates the biomarker.

Abstract: Compounds of Formula (I) or pharmaceutically acceptable salts thereof are provided and methods involving compounds of Formula (I) as effective inhibitors of CDK8 and/or CDK19 are also provided.

Abstract: The present invention provides methods of predicting cell sensitivity or resistance to a therapeutic agent.

Abstract: The application relates to a compound having Formula I: which modulates the activity of HER2 and/or a mutant thereof, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which HER2 and/or a mutant thereof plays a role.

Abstract: Disclosed are bispecific compounds (degraders) that target cereblon (CRBN) for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds as research tools and to reduce adverse side effects associated with a cereblon targeted therapy.

Abstract: Presently described are methods for enriching regions of a genome in a sample using ligation of fragmented genomic nucleic acid and amplification using repeat elements. The methods can be used for a number of applications, including genome-wide homopolymer indel detection, and enable increasing the amount of information obtained from a limited sample of genomic nucleic acid.

Abstract: A method for detecting oncogenic growth and viability, and/or degree of cellular transformation and/or identifying an agent that inhibits cellular transformation is disclosed. The method including: providing a cellular sample, such as a sample of cells obtained from a subject or a cell line; culturing the cellular sample in low attachment conditions; and detecting growth and7or cell viability of the sample, wherein increased growth relative and/or viability relative to a control or control level indicative of basal growth and/or viability indicates cellular transformation. In some embodiments, the method includes introducing a n expression vector into cells of the cellular sample, wherein the expression vector comprises a gene product expression sequence being tested for transformation ability. In some embodiments the cellular sample is contacted with a test agent and growth and/or cell viability of the sample is determined to determine if the agent inhibits transformation.

Abstract: DCAF15 is a substrate recognition (adaptor) protein of E3 ubiquitin ligase. Disclosed herein are compounds that recruit ubiquitin ligase CRL4DCAF15, to a target RNA recognition motif (RRM), causing its degradation. Also disclosed herein are compositions and methods of use in treating associated disorders and diseases.