Medicament for treatment of tumors wherein hedgehog/smoothened signaling is employed for inhibition of apoptosis of the tumor cells
0 Assignments
0 Petitions
Accused Products
Abstract
This invention concerns the use of cyclopamine in vivo on basal cell carcinomas (BCC'"'"'s) to achieve therapeutic effect by causing differentiation of the tumor cells and, at the same time, apoptotic death and removal of these tumor cells while preserving the normal tissue cells, including the undifferentiated cells of the normal epidermal basal layer and hair follicles. Causation of apoptosis by cyclopamine is by a non-genotoxic mechanism and thus unlike the radiation therapy and most of the currently used cancer chemotherapeutics which act by causing DNA-damage. These novel effects, previously unachieved by a cancer chemotherapeutic, make the use of cyclopamine highly desirable in cancer therapy, in the treatment of BCC'"'"'s and other tumors that use the hedgehog/smoothened signal transduction pathway for proliferation and prevention of apoptosis.
55 Citations
38 Claims
-
1-24. -24. (canceled)
-
25. A medicament for causing decrease of size or disappearance of a tumor in a tumor-bearing subject,
wherein Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of the tumor cells, wherein the medicament comprises cyclopamine or a pharmaceutically acceptable salt thereof or another compound that selectively inhibits Hedgehog/Smoothened signaling, wherein the medicament has labeling that instructs administration to the subject in a dose that suffices for induction of apoptosis of the tumor cells and for decrease of size or disappearance of the tumor.
-
26. A medicament for causing decrease of size or disappearance of a tumor in a human,
wherein Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of the tumor cells, wherein the medicament comprises cyclopamine or a pharmaceutically acceptable salt thereof or another compound that selectively inhibits Hedgehog/Smoothened signaling, wherein the medicament has labeling that instructs administration to said human in a dose that suffices for induction of apoptosis of the tumor cells and for decrease of size or disappearance of the tumor.
-
27. A medicament for causing decrease of size or disappearance of a tumor in a human,
wherein Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of the tumor cells, wherein the medicament comprises cyclopamine or a pharmaceutically acceptable salt thereof or another compound that selectively inhibits Hedgehog/Smoothened signaling, wherein the medicament has labeling that instructs administration to said human in a dose that suffices for induction of apoptosis of the tumor cells and for decrease of size or disappearance of the tumor, and wherein administration as instructed in the labeling induces apoptosis of the tumor cells and results in decrease of size or disappearance of the tumor.
-
28. A medicament for causing decrease of size or disappearance of a tumor in a human,
wherein Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of the tumor cells, wherein the medicament comprises cyclopamine or a pharmaceutically acceptable salt thereof or another compound that selectively inhibits Hedgehog/Smoothened signaling, wherein the medicament has labeling that instructs administration to said human in a dose that suffices for induction of apoptosis of the tumor cells and for decrease of size or disappearance of the tumor, wherein said administration causes decrease of size or disappearance of the tumor by inducing apoptosis of the tumor cells while sparing normal cells of said human that are labeled by an antibody that marks both the tumor cells and normal cells having stem cell features.
-
29. A medicament for treatment of a tumor-bearing human,
wherein the tumor is one wherein Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of tumor cells, wherein the medicament comprises cyclopamine or a pharmaceutically acceptable salt thereof or another compound that selectively inhibits Hedgehog/Smoothened signaling, wherein the medicament has instructions of administration effective for induction of apoptosis of the tumor cells and for decrease of size or disappearance of the tumor, wherein administration as instructed to said human induces apoptosis of the tumor cells and results in decrease of size or disappearance of the tumor.
-
30. A medicament comprising cyclopamine or a pharmaceutically acceptable salt thereof or another compound that selectively inhibits Hedgehog/Smoothened signaling,
wherein the medicament has labeling that instructs administration to a tumor-bearing human, wherein the tumor is one wherein Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of the tumor cells, wherein the instructions comprises administration in a dose that is sufficient for induction of apoptosis of the tumor cells and for decrease of size or disappearance of the tumor, wherein said administration causes decrease of size or disappearance of the tumor by inducing apoptosis of the tumor cells while sparing normal cells of said human that are labeled by an antibody that marks both the tumor cells and normal cells having stem cell features.
-
36. A kit or labeled container comprising
(i) cyclopamine or a pharmaceutically acceptable salt thereof or another compound that selectively inhibits Hedgehog/Smoothened signaling and (ii) instructions secured to the container or associated with the kit or container and giving directions for administration of cyclopamine or of said salt or of said another compound to a tumor-bearing subject, wherein the tumor is one wherein Hedgehog/Smoothened signaling is utilized for inhibition of apoptosis of tumor cells, wherein the instructions comprises administration of cyclopamine or of said salt or of said another compound in a dose that is sufficient for induction of apoptosis of the tumor cells and for decrease of size or disappearance of the tumor, and wherein administration as instructed induces apoptosis of the tumor cells and results in decrease of size or disappearance of the tumor.
Specification