The present disclosure, relates, in general to methods for treating solid tumors comprising administering a drug-linker-antibody conjugate, wherein the drug is a tubulin disrupting agent.

The present disclosure, relates, in general to methods for treating solid tumors comprising administering a drug-linker-antibody conjugate, wherein the drug is a tubulin disrupting agent.

The present invention generally relates to tumor homing statin derivatives (THSD) and their use for therapy, in particular cancer therapy. These THSD comprise three moieties: a statin moiety which comprises a dihydroxyheptanoic acid unit (DHHA) fixated by linkage into its open chain form, a heptamethine carbocyanine dye (HMCD) moiety, and a linker that conjugates the DHHA of the statin to the dye moiety. The linker is linked to the DHHA via an ester bond (ester-linked statin derivative or ELSD), or via an amide bond (amide-linked statin derivative or ALSD). Thus linked to the DHHA, the linker provides a relatively stable link either for essentially no hydrolysis/statin release after administration, or preferably for very slow hydrolysis and statin release, as is the case for the ELSD. Embodiments include methods to provide the desired THSD, in particular the ELSD, with the DHHA in its open chain form. The invention also relates to methods wherein one or more ELSD is administered to a patient in a therapeutically effective amount, and methods wherein an ELSD and an ALSD are co-administered in a coordinated administration schedule. Advantages of the THSD and their use include, among others, improved efficacy and dose-response, and decreased statin-associated side effects.

The present invention generally relates to tumor homing statin derivatives (THSD) and their use for therapy, in particular cancer therapy. These THSD comprise three moieties: a statin moiety which comprises a dihydroxyheptanoic acid unit (DHHA) fixated by linkage into its open chain form, a heptamethine carbocyanine dye (HMCD) moiety, and a linker that conjugates the DHHA of the statin to the dye moiety. The linker is linked to the DHHA via an ester bond (ester-linked statin derivative or ELSD), or via an amide bond (amide-linked statin derivative or ALSD). Thus linked to the DHHA, the linker provides a relatively stable link either for essentially no hydrolysis/statin release after administration, or preferably for very slow hydrolysis and statin release, as is the case for the ELSD. Embodiments include methods to provide the desired THSD, in particular the ELSD, with the DHHA in its open chain form. The invention also relates to methods wherein one or more ELSD is administered to a patient in a therapeutically effective amount, and methods wherein an ELSD and an ALSD are co-administered in a coordinated administration schedule. Advantages of the THSD and their use include, among others, improved efficacy and dose-response, and decreased statin-associated side effects.

The invention provides methods of treating a cancer in a subject, comprising administering to the subject a combination of (a) an anti-neoplastic agent and (b) an agent that induces iron-dependent cellular disassembly, thereby treating the cancer in the subject. In some embodiments, the cancer is resistant to the anti-neoplastic agent.

The invention provides methods of treating a cancer in a subject, comprising administering to the subject a combination of (a) an anti-neoplastic agent and (b) an agent that induces iron-dependent cellular disassembly, thereby treating the cancer in the subject. In some embodiments, the cancer is resistant to the anti-neoplastic agent.

The present invention involves a method of treating pain. The method treats a patient having post-operative pain or chemotherapy induced neuropathic pain, and it involves a) assessing the patient to determine if they are experiencing post-operative pain or chemotherapy induced neuropathic pain, and if such pain is diagnosed; b) administering to the patient a therapeutically effective amount of an agonist for the nuclear receptor subfamily 4, group A, member 1 (NR4A1). In one embodiment, the agonist is selected from the group consisting of Cytosporone B, Ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)-phenyl] acetate (TMPA), 1,3,7-trihydroxy-2,4-diprenylxanthone (CCE9), 1-(3,4,5-trihydroxyphenyl)-nonan-1-one (THPN), DIM-C-pPhOCH3 (C-DIM-5), 1,1-bis(3′-indolyl)-1-(phenyl)methane (DIM-C-Ph) and 1,1-bis(3′-indolyl)-1-(p-anisyl)methane (DIM-C-pPhOCH.sub.3).

The present invention involves a method of treating pain. The method treats a patient having post-operative pain or chemotherapy induced neuropathic pain, and it involves a) assessing the patient to determine if they are experiencing post-operative pain or chemotherapy induced neuropathic pain, and if such pain is diagnosed; b) administering to the patient a therapeutically effective amount of an agonist for the nuclear receptor subfamily 4, group A, member 1 (NR4A1). In one embodiment, the agonist is selected from the group consisting of Cytosporone B, Ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)-phenyl] acetate (TMPA), 1,3,7-trihydroxy-2,4-diprenylxanthone (CCE9), 1-(3,4,5-trihydroxyphenyl)-nonan-1-one (THPN), DIM-C-pPhOCH3 (C-DIM-5), 1,1-bis(3′-indolyl)-1-(phenyl)methane (DIM-C-Ph) and 1,1-bis(3′-indolyl)-1-(p-anisyl)methane (DIM-C-pPhOCH.sub.3).

The present invention involves a method of treating pain. The method treats a patient having post-operative pain or chemotherapy induced neuropathic pain, and it involves a) assessing the patient to determine if they are experiencing post-operative pain or chemotherapy induced neuropathic pain, and if such pain is diagnosed; b) administering to the patient a therapeutically effective amount of an agonist for the nuclear receptor subfamily 4, group A, member 1 (NR4A1). In one embodiment, the agonist is selected from the group consisting of Cytosporone B, Ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)-phenyl] acetate (TMPA), 1,3,7-trihydroxy-2,4-diprenylxanthone (CCE9), 1-(3,4,5-trihydroxyphenyl)-nonan-1-one (THPN), DIM-C-pPhOCH3 (C-DIM-5), 1,1-bis(3′-indolyl)-1-(phenyl)methane (DIM-C-Ph) and 1,1-bis(3′-indolyl)-1-(p-anisyl)methane (DIM-C-pPhOCH.sub.3).

This disclosure is directed to treatment of addictions and primary impulse-control disorders using phosphodiesterase 7 (PDE7) inhibitors, alone or in combination with other therapeutic agents.