The present disclosure provides for methods and compositions for treating cancer. A subject having lymphoma is administered an EZH2 inhibitor and an HDAC inhibitor. The combination of the EZH2 inhibitor and the HDAC inhibitor produces a synergistic effect on the cancer compared to the effect of the EZH2 inhibitor or the HDAC inhibitor alone.

Provided herein are combinations that include an HDACi and a PD-1 inhibitor that are useful for treating cancer, including reducing and/or preventing cancer metastasis. The combination is also useful for treating cancer that has been previously treated with a PD-L1 inhibitor.

Provided herein are combinations that include an HDACi and a PD-1 inhibitor that are useful for treating cancer, including reducing and/or preventing cancer metastasis. The combination is also useful for treating cancer that has been previously treated with a PD-L1 inhibitor.

The present disclosure provides compositions and methods for treating subjects at risk for or with sensorineural hearing loss by modulating the rate of Atoh1 protein degradation to increase levels of Atoh1 protein.

The present disclosure provides methods for treating Adult T-cell Leukemia/Lymphoma (ATLL) in a subject by administering to the subject an oligonucleotide inhibitor of miR-155. In some embodiments, the subject may have received one or more therapies for treating ATLL prior to receiving the oligonucleotide inhibitor of miR-155. Administration of an oligonucleotide inhibitor of miR-155 according to the methods of the present disclosure can decrease the tumor cell count or can maintain the tumor cell count at or below the tumor cell count at the beginning of administration of the oligonucleotide inhibitor of miR-155. Accordingly, the methods provided in this disclosure can be used as maintenance therapies for treating ATLL subjects.

The present disclosure provides methods for treating Adult T-cell Leukemia/Lymphoma (ATLL) in a subject by administering to the subject an oligonucleotide inhibitor of miR-155. In some embodiments, the subject may have received one or more therapies for treating ATLL prior to receiving the oligonucleotide inhibitor of miR-155. Administration of an oligonucleotide inhibitor of miR-155 according to the methods of the present disclosure can decrease the tumor cell count or can maintain the tumor cell count at or below the tumor cell count at the beginning of administration of the oligonucleotide inhibitor of miR-155. Accordingly, the methods provided in this disclosure can be used as maintenance therapies for treating ATLL subjects.

The present disclosure relates to a binding molecule binding to L1, which is capable of binding to the same L1 epitope recognized by the monoclonal antibody L1-OV52.24, and/or which competes with the monoclonal antibody L1-OV52.24 for binding to L1, wherein the variable part of the light chain of L1-OV52.24 comprises the sequence according to SEQ ID No: 1 or wherein the light chain is encoded by SEQ ID No: 3, and wherein the variable part of the heavy chain of L1-OV52.24 comprises the sequence according to SEQ ID No: 2 or wherein the heavy chain is encoded by SEQ ID No: 4, nucleic acids encoding the binding molecules, uses thereof and pharmaceutical compositions comprising the binding molecules.

The present disclosure relates to a binding molecule binding to L1, which is capable of binding to the same L1 epitope recognized by the monoclonal antibody L1-OV52.24, and/or which competes with the monoclonal antibody L1-OV52.24 for binding to L1, wherein the variable part of the light chain of L1-OV52.24 comprises the sequence according to SEQ ID No: 1 or wherein the light chain is encoded by SEQ ID No: 3, and wherein the variable part of the heavy chain of L1-OV52.24 comprises the sequence according to SEQ ID No: 2 or wherein the heavy chain is encoded by SEQ ID No: 4, nucleic acids encoding the binding molecules, uses thereof and pharmaceutical compositions comprising the binding molecules.

A method of treating lymphoma in a mammal comprises the step of: administering to a patient a pharmaceutical acceptable amount of a compound being a thienotriazolodiazepine compound of the Formula (1) wherein R.sup.1 is alkyl having a carbon number of 1-4, R.sup.2 is a hydrogen atom; a halogen atom; or alkyl having a carbon number of 1-4 optionally substituted by a halogen atom or a hydroxyl group, R.sup.3 is a halogen atom; phenyl optionally substituted by a halogen atom, alkyl having a carbon number of 1-4, alkoxy having a carbon number of 1-4 or cyano; —NR.sup.5—(CH.sub.2).sub.m—R.sup.6 wherein R.sup.5 is a hydrogen atom or alkyl having a carbon number of 1-4, m is an integer of 0-4, and R.sup.6 is phenyl or pyridyl optionally substituted by a halogen atom; or —NR.sup.7—CO—(CH.sub.2).sub.q—R.sup.8 wherein R is a hydrogen atom or alkyl having a carbon number of 1-4, n is an integer of 0-2, and R.sup.8 is phenyl or pyridyl optionally substituted by a halogen atom, and R.sup.4 is —(CH.sub.2).sub.a—CO—NH—R.sup.9 wherein a is an integer of 1-4, and R.sup.9 is alkyl having a carbon number of 1-4; hydroxyalkyl having a carbon number of 1-4; alkoxy having a carbon number of 1-4; or phenyl or pyridyl optionally substituted by alkyl having a carbon number of 1-4, alkoxy having a carbon number of 1-4, amino or a hydroxyl group or —(CH.sub.2).sub.b—COOR.sup.10 wherein b is an integer of 1-4, and R.sup.10 is alkyl having a carbon number of 1-4, or a pharmaceutically acceptable salt thereof or a hydrate or solvate thereof. The lymphoma to be treated is diffuse large B-cell lymphom (DLB-CL) specifically selected from activated B-cell DLBCL (ABC-DLBCL) and germinal B-cell DLBCL (GBC-DLBCL).

##STR00001##

A method of treating lymphoma in a mammal comprises the step of: administering to a patient a pharmaceutical acceptable amount of a compound being a thienotriazolodiazepine compound of the Formula (1) wherein R.sup.1 is alkyl having a carbon number of 1-4, R.sup.2 is a hydrogen atom; a halogen atom; or alkyl having a carbon number of 1-4 optionally substituted by a halogen atom or a hydroxyl group, R.sup.3 is a halogen atom; phenyl optionally substituted by a halogen atom, alkyl having a carbon number of 1-4, alkoxy having a carbon number of 1-4 or cyano; —NR.sup.5—(CH.sub.2).sub.m—R.sup.6 wherein R.sup.5 is a hydrogen atom or alkyl having a carbon number of 1-4, m is an integer of 0-4, and R.sup.6 is phenyl or pyridyl optionally substituted by a halogen atom; or —NR.sup.7—CO—(CH.sub.2).sub.q—R.sup.8 wherein R is a hydrogen atom or alkyl having a carbon number of 1-4, n is an integer of 0-2, and R.sup.8 is phenyl or pyridyl optionally substituted by a halogen atom, and R.sup.4 is —(CH.sub.2).sub.a—CO—NH—R.sup.9 wherein a is an integer of 1-4, and R.sup.9 is alkyl having a carbon number of 1-4; hydroxyalkyl having a carbon number of 1-4; alkoxy having a carbon number of 1-4; or phenyl or pyridyl optionally substituted by alkyl having a carbon number of 1-4, alkoxy having a carbon number of 1-4, amino or a hydroxyl group or —(CH.sub.2).sub.b—COOR.sup.10 wherein b is an integer of 1-4, and R.sup.10 is alkyl having a carbon number of 1-4, or a pharmaceutically acceptable salt thereof or a hydrate or solvate thereof. The lymphoma to be treated is diffuse large B-cell lymphom (DLB-CL) specifically selected from activated B-cell DLBCL (ABC-DLBCL) and germinal B-cell DLBCL (GBC-DLBCL).

##STR00001##