Combination therapies that include (i) an immune cell that expresses a chimeric antigen receptor (CAR) or similar molecule and (ii) a compound that preserves or potentiates the in vivo actions of tumor necrosis factor alpha (TNFα) against cancer cells are described. The combination therapies result in the killing of antigen-negative cells in the vicinity of immunotherapy targeted-antigen-positive cells reducing the survivability of escape variants and providing other benefits.

Novel rapamycin analogs and uses thereof are disclosed herein. The rapamycin analogs of the present disclosure show increased mTORC1 specificity and lowered mTORC2 specificity relative to rapamycin.

Novel rapamycin analogs and uses thereof are disclosed herein. The rapamycin analogs of the present disclosure show increased mTORC1 specificity and lowered mTORC2 specificity relative to rapamycin.

The present invention relates to the compound of formula (I) wherein R.sup.1A, R.sup.1B, R.sup.1C, and R.sup.1D are hydrogen atom, etc., R.sup.2A and R.sup.2B are hydrogen atom, etc., R.sup.3A, R.sup.3B, R.sup.3C, and R.sup.3D are hydrogen atom, etc., L is bond, etc., V is C.sub.1-6 alkylene, Q is optionally-substituted imidazole, or a pharmaceutically acceptable salt thereof, as a novel anti-tumor agent that targets CSCs which are thought to be closely involved in the persistent proliferation of malignant tumor, metastasis or recurrence of cancer, and resistance to anti-tumor agents.

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Provided herein are methods of treating neurodevelopmental disorders, including the treatment of Tuberous sclerosis complex (TSC), with pharmaceutical compositions containing heat shock protein (Hsp) inhibitors and/or mTOR inhibitors. Also provided herein are methods for inhibiting mechanistic target of rapamycin complex 1 (mTORC1) activity and/or increasing or normalizing ciliation.

The present invention relates, inter alia, to a method of preventing or treating skin cancer or skin precancer, the method comprising locally administering to the skin of a subject in need thereof an effective amount of a compound of Formula (I) or a pro-drug thereof, Formula (I) wherein the subject is being administered an immunosuppressant agent that binds to FKBP12. The agent that binds to FKBP12 may be tacrolimus. The invention also relates to methods of preventing or treating a skin condition, disorder or disease associated with administration of an immunosuppressant agent that binds to FKBP12, and to uses of the compound of Formula (I) in treating skin cancer or skin precancer, or a skin condition, disorder or disease associated with administration of an immunosuppressant agent that binds to FKBP12.

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The present invention relates, inter alia, to a method of preventing or treating skin cancer or skin precancer, the method comprising locally administering to the skin of a subject in need thereof an effective amount of a compound of Formula (I) or a pro-drug thereof, Formula (I) wherein the subject is being administered an immunosuppressant agent that binds to FKBP12. The agent that binds to FKBP12 may be tacrolimus. The invention also relates to methods of preventing or treating a skin condition, disorder or disease associated with administration of an immunosuppressant agent that binds to FKBP12, and to uses of the compound of Formula (I) in treating skin cancer or skin precancer, or a skin condition, disorder or disease associated with administration of an immunosuppressant agent that binds to FKBP12.

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The present invention relates, inter alia, to a method of preventing or treating skin cancer or skin precancer, the method comprising locally administering to the skin of a subject in need thereof an effective amount of a compound of Formula (I) or a pro-drug thereof, Formula (I) wherein the subject is being administered an immunosuppressant agent that binds to FKBP12. The agent that binds to FKBP12 may be tacrolimus. The invention also relates to methods of preventing or treating a skin condition, disorder or disease associated with administration of an immunosuppressant agent that binds to FKBP12, and to uses of the compound of Formula (I) in treating skin cancer or skin precancer, or a skin condition, disorder or disease associated with administration of an immunosuppressant agent that binds to FKBP12.

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To provide a method for treating cancer using a pyrazolo[3,4-d]pyrimidine compound or a salt thereof. The present invention provides an antitumor agent comprising a pyrazolo[3,4-d]pyrimidine compound of formula (I) wherein X, Y, Z.sub.1, Z.sub.2, Z.sub.3, Z.sub.4, W, n, R.sub.1, R.sub.2, and R.sub.3 have meanings as defined in the present specification, or a salt thereof and other antitumor agent(s) for combined administration.

To provide a method for treating cancer using a pyrazolo[3,4-d]pyrimidine compound or a salt thereof. The present invention provides an antitumor agent comprising a pyrazolo[3,4-d]pyrimidine compound of formula (I) wherein X, Y, Z.sub.1, Z.sub.2, Z.sub.3, Z.sub.4, W, n, R.sub.1, R.sub.2, and R.sub.3 have meanings as defined in the present specification, or a salt thereof and other antitumor agent(s) for combined administration.