In some embodiments the present invention provides methods useful for the treatment of MMR-proficient and/or microsatellite stable (MSS) cancers and also useful for enhancing the immunogenicity of MMR-proficient and/or microsatellite stable (MSS) cancer cells, enhancing the sensitivity of MMR-proficient and/or microsatellite stable (MSS) cancer cells to immune checkpoint blockade, inducing an MMR-deficient mutational signature in MMR-proficient and/or microsatellite stable (MSS) cancer cells, and/or increasing the frequency of both missense and InDel mutations in MMR-proficient and/or microsatellite stable (MSS) cancer cells. In some embodiments such methods involve administration of a combination of temozolomide and cisplatin, or a combination of temozolomide, cisplatin and an immune checkpoint inhibitor, to a subject in need thereof.

In some embodiments the present invention provides methods useful for the treatment of MMR-proficient and/or microsatellite stable (MSS) cancers and also useful for enhancing the immunogenicity of MMR-proficient and/or microsatellite stable (MSS) cancer cells, enhancing the sensitivity of MMR-proficient and/or microsatellite stable (MSS) cancer cells to immune checkpoint blockade, inducing an MMR-deficient mutational signature in MMR-proficient and/or microsatellite stable (MSS) cancer cells, and/or increasing the frequency of both missense and InDel mutations in MMR-proficient and/or microsatellite stable (MSS) cancer cells. In some embodiments such methods involve administration of a combination of temozolomide and cisplatin, or a combination of temozolomide, cisplatin and an immune checkpoint inhibitor, to a subject in need thereof.

In some embodiments the present invention provides methods useful for the treatment of MMR-proficient and/or microsatellite stable (MSS) cancers and also useful for enhancing the immunogenicity of MMR-proficient and/or microsatellite stable (MSS) cancer cells, enhancing the sensitivity of MMR-proficient and/or microsatellite stable (MSS) cancer cells to immune checkpoint blockade, inducing an MMR-deficient mutational signature in MMR-proficient and/or microsatellite stable (MSS) cancer cells, and/or increasing the frequency of both missense and InDel mutations in MMR-proficient and/or microsatellite stable (MSS) cancer cells. In some embodiments such methods involve administration of a combination of temozolomide and cisplatin, or a combination of temozolomide, cisplatin and an immune checkpoint inhibitor, to a subject in need thereof.

Methods and compositions for treating a subject suffering from adrenocortical carcinoma and having excess cortisol are disclosed. The methods provide therapeutic benefits including reduction of ACC tumor load, restoration of T-cell and natural killer (NK) cell signaling pathways, increase in T-cell and NK cell infiltration into the ACC tumor, reduction of neutrophil infiltration into the ACC tumor in the patient, and other therapeutic benefits. The methods include administration of a glucocorticoid receptor modulator (GRM) (which may be a selective glucocorticoid receptor modulator (SGRM)) and an antibody checkpoint inhibitor. In embodiments, the GRM (e.g., a SGRM) is orally administered. The GRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure.

Methods and compositions for treating a subject suffering from adrenocortical carcinoma and having excess cortisol are disclosed. The methods provide therapeutic benefits including reduction of ACC tumor load, restoration of T-cell and natural killer (NK) cell signaling pathways, increase in T-cell and NK cell infiltration into the ACC tumor, reduction of neutrophil infiltration into the ACC tumor in the patient, and other therapeutic benefits. The methods include administration of a glucocorticoid receptor modulator (GRM) (which may be a selective glucocorticoid receptor modulator (SGRM)) and an antibody checkpoint inhibitor. In embodiments, the GRM (e.g., a SGRM) is orally administered. The GRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure.

The present disclosure describes, in part, compositions and methods for treating pathologic pains associated with malignant growth disorders by administering a therapeutically effective amount of K+/Cl-cotransporter (Kcc2/KCC2) gene expression enhancer to a subject in need.

The present disclosure describes, in part, compositions and methods for treating pathologic pains associated with malignant growth disorders by administering a therapeutically effective amount of K+/Cl-cotransporter (Kcc2/KCC2) gene expression enhancer to a subject in need.

A method for treatment of a tumor includes obtaining 3D imaging of the tumor; processing the 3D imaging of the tumor to obtain tumor morphology; determining a number of treatment sites, the locations of such sites, and the treatment dosage using a model of intratumoral treatment dynamics between vascular, intracellular, and extracellular space in order for the tumor to receive a therapeutic dosage at every location of the tumor; and treating the tumor at each of the determined treatment sites and with the determined treatment dosage. In some embodiments, the method further includes generating the model to include a plurality of interconnected volumes wherein each volume has one or more adjacent volumes with a shared boundary. One or more simulations of treatment over time may be conducted using the model, each simulation having a set of one or more initial parameters.

The present invention aims to provide a method of acquiring data for determination of, and a method of acquiring prediction data on the presence of cancer cells and/or the resistance to anticancer drugs, use of a marker for determining thereof, and a kit for determining thereof, in particular, to determine the resistance to anticancer drugs before administration of the anticancer drugs to patients. The resistance of cancer tissues of cancer patients to anticancer drugs can be determined by detecting polysulfide, which is a marker for the resistance to anticancer drugs, in the cancer tissues of the cancer patients before administration of the anticancer drugs.

The present invention aims to provide a method of acquiring data for determination of, and a method of acquiring prediction data on the presence of cancer cells and/or the resistance to anticancer drugs, use of a marker for determining thereof, and a kit for determining thereof, in particular, to determine the resistance to anticancer drugs before administration of the anticancer drugs to patients. The resistance of cancer tissues of cancer patients to anticancer drugs can be determined by detecting polysulfide, which is a marker for the resistance to anticancer drugs, in the cancer tissues of the cancer patients before administration of the anticancer drugs.