Abstract: By combining temozolomide with a mutant IDH1 enzyme inhibitor, it was discovered that the dosage of temozolomide could be reduced without decreasing the antitumor effect, enabling us to provide a combination drug with excellent efficacy against cancers with IDH1 mutations.

Abstract: It is intended to provide a medicament and a method for treating cancer comprising a compound having MDM2 inhibiting activity and a compound having FLT3 inhibiting activity in combination. The present invention provides a medicament comprising (3?R,4?S,5?R)—N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6?-chloro-4?-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-2?-oxo-1?,2?-dihydrodispiro[cyclohexane-1,2?-pyrrolidine-3?,3?-indole]-5?-carboxamide or a pharmaceutically acceptable salt thereof and N-(5-tert-butyl-isoxazol-3-yl)-N?-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea or a pharmaceutically acceptable salt thereof in combination, and a treatment method using these compounds or salts in combination.

Abstract: It is intended to provide a medicament and a method for treating cancer comprising a compound having MDM2 inhibiting activity and a compound having BTK inhibiting activity in combination. The present invention provides a medicament comprising (3?R,4?S,5?R)—N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6?-chloro-4?-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-2?-oxo-1?,2?-dihydrodispiro[cyclohexane-1,2?-pyrrolidine-3?,3?-indole]-5?-carboxamide or a pharmaceutically acceptable salt thereof and ibrutinib or a pharmaceutically acceptable salt thereof in combination, and a treatment method using these compounds or salts in combination.

Abstract: It is intended to provide a medicament and a method for treating cancer, comprising a compound having MDM2 inhibiting activity and a DNA methyltransferase inhibitor in combination. The present invention provides a medicament comprising (3?R,4?S,5?R)—N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6?-chloro-4?-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-2?-oxo-1?,2?-dihydrodispiro[cyclohexane-1,2?-pyrrolidine-3?,3?-indole]-5?-carboxamide or a pharmaceutically acceptable salt thereof and a DNA methyltransferase inhibitor in combination, and a treatment method using the compound or a salt thereof and a DNA methyltransferase inhibitor in combination.

Abstract: It is intended to provide a medicament and a method for treating cancer comprising a compound having MDM2 inhibiting activity and a compound having BTK inhibiting activity in combination. The present invention provides a medicament comprising (3?R,4?S,5?R)-N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6?-chloro-4?-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-2?-oxo-1?,2?-dihydrodispiro[cyclohexane-1,2?-pyrrolidine-3?,3?-indole]-5?-carboxamide or a pharmaceutically acceptable salt thereof and ibrutinib or a pharmaceutically acceptable salt thereof in combination, and a treatment method using these compounds or salts in combination.

Abstract: The present invention provides a pharmaceutical composition for use in treating acute myeloid leukemia (AML) and a method of treating AML in a patient in need thereof. The present invention also provides a method for predicting the sensitivity to the treatment in the patient using gene expression signature.

Abstract: It is intended to provide a medicament and a method for treating cancer comprising a compound having MDM2 inhibiting activity and a compound having BTK inhibiting activity in combination. The present invention provides a medicament comprising (3?R,4?S,5?R)-N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6?-chloro-4?-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-2?-oxo-1?,2?-dihydrodispiro[cyclohexane-1,2?-pyrrolidine-3?,3?-indole]-5?-carboxamide or a pharmaceutically acceptable salt thereof and ibrutinib or a pharmaceutically acceptable salt thereof in combination, and a treatment method using these compounds or salts in combination.

Abstract: Provided are gene signatures that are predictive of the sensitivity of a cancer or tumor to an MDM2i or an antagonist of the MDM2-p53 interaction. Differentially expressed genes in the provided gene signatures serve as biomarkers for determining and assessing the sensitivity of cancer and tumor samples to treatment or therapy with an MDM2i. Also provided are methods of determining MDM2i sensitivity of a test sample such as different cancer and tumor types and subtypes, based on the expression of genes in the MDM2i sensitive gene signatures in reference samples and the test sample even if all of the MDM2i sensitivities of the reference samples are unknown, and treating individuals with an MDM2i if their cancers are determined to be MDM2i-sensitive, based on the practice of the described methods. TP53 gene and p53 protein status can also be determined for the samples undergoing analysis for MDM2i sensitivity.

Abstract: It is intended to provide a medicament and a method for treating cancer comprising a compound having MDM2 inhibiting activity and a compound having FLT3 inhibiting activity in combination. The present invention provides a medicament comprising (3?R,4?S,5?R)—N-[(3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl]-6?-chloro-4?-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-2?-oxo-1?,2?-dihydrodispiro[cyclohexane-1,2?-pyrrolidine-3?,3?-indole]-5?-carboxamide or a pharmaceutically acceptable salt thereof and N-(5-tert-butyl-isoxazol-3-yl)-N?-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea or a pharmaceutically acceptable salt thereof in combination, and a treatment method using these compounds or salts in combination.

Abstract: Gene signatures that are predictive of the sensitivity of a cancer or tumor to an MDM2i or an antagonist of the MDM2-p53 interaction. Differentially expressed genes in the provided gene signatures serve as biomarkers assessing the sensitivity of cancer and tumor samples to treatment or therapy with an MDM2i. Also provided are methods of determining MDM2i sensitivity of different cancer and tumor types and subtypes, based on the expression of genes in the MDM2i sensitive gene signatures, and treating individuals with an MDM2i if their cancers are determined to be MDM2i-sensitive. TP53 gene and p53 protein status can be determined for the samples undergoing analysis for MDM2i sensitivity. Methods, platforms, kits, reagents, and compositions of the invention provide advantageous approaches and tools for personalized or individualized treatments of cancer patients whose cancers exhibit sensitivity to MDM2 inhibitors.