System and method for diagnosis and treatment
This invention relates the use of cortisol blockers (glucocorticoid receptor [GR] antagonists) for the treating or preventing treatment resistant prostate cancer, treating or preventing neoplasia, and treating or preventing infection related to acute or chronic injury or disease.
1. A method for treating neoplasia characterized by expression of a glucocorticoid receptor, in a patient in need of such treatment, comprising:
administering to said patient at least one therapeutically effective neoplasia-treating therapy, and
wherein the GCR antagonist is ORG34517 ((11β,17β)-11-(1,3-benzodioxol-5-yl)-17-hydroxy-17-(1-propynyl) estra-4,9-dien-3-one) which has the following formula:
wherein the administration of ORG 34517 for GR-blockade, reduces toxicities and side effects when given systemically,
thereby treating said animal or human.
2. The method of claim 1 , wherein the neoplasia is selected from the group consisting of hepatocellular carcinoma, esophageal squamous cell carcinoma, breast cancer, pancreatic cancer, squamous cell cancer or adenocarcinoma of the head and neck, colorectal cancer, renal cancer, brain cancer, small and non-small cell lung cancer, bladder cancer, bone or joint cancer, uterine cancer, cervical cancer, multiple myeloma, hematopoietic malignancies, lymphoma, Hodgkin's disease, non-Hodgkin's lymphoma, skin cancer, melanoma, squamous cell carcinoma, leukemia, lung cancer, ovarian cancer, stomach cancer, Kaposi's sarcoma, laryngeal cancer, endocrine carcinomas, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the pituitary gland, cancer of the adrenal gland, and combinations thereof.
3. The method of claim 1 , wherein the neoplasia is chemo-resistant ER/GR+ breast cancer.
4. The method of claim 1 wherein said neoplasia-treating therapy is radiation.
5. The method of claim 1 wherein said neoplasia-treating therapy is a radionuclide.
6. The method of claim 1 wherein said neoplasia treating therapy is selected from the group consisting of X-rays, gamma rays, and other sources of radiation.
7. The method of claim 1 wherein said neoplasia treating therapy is radiation therapy administered as external beam radiation, wherein the radiation is directed from a remote source.
8. The method of claim 1 wherein said neoplasia treating therapy is radiation therapy administered as brachytherapy wherein a radioactive source is placed inside the body close to cancer stem cells, cancer cells, and/or a tumor mass.
9. The method of claim 1 wherein the method comprises administration of a neoplasia treating therapy followed by the administration of the GCR antagonist ORG34517.
10. The method of claim 1 wherein the method comprises administration of a neoplasia treating therapy and the administration of the GCR antagonist ORG34517 concurrently.
11. The method of claim 1 wherein the method comprises administration of the GCR antagonist ORG34517 followed by the administration of a neoplasia treating therapy.
12. The method of claim 1 wherein said neoplasia treating therapy comprises both radiation therapy and an additional neoplasia treating therapy.
13. The method of claim 1 wherein said additional neoplasia treating therapy is selected from the group consisting of peptides, polypeptides, fusion proteins, nucleic acid molecules, small molecules, mimetic agents, synthetic drugs, inorganic molecules, organic molecules, hormonal therapies, anti-angiogenesis therapies, targeted therapies, biological therapies, immunotherapy, and surgery.
14. The method of claim 1 , wherein the ORG 34517 given systemically through oral or intravenous routes.
15. The method of claim 1 , wherein the ORG 34517 is given to accomplish cure or remission of tumor.
16. The method of claim 1 , wherein the ORG 34517 is given to accomplish reduction of tumor burden to enhance effectiveness of subsequent surgical resection.
17. A method for treating neoplasia in a patient in need of such treatment, the method comprising:
a) administering to said patient a therapeutically effective amount of ORG 34517; and
b) administering to said patient at least one therapeutically effective neoplasia-treating therapy,
thereby treating said patient.
18. The method of claim 17 , wherein the neoplasia is selected from the group consisting of hepatocellular carcinoma, esophageal squamous cell carcinoma, breast cancer, pancreatic cancer, squamous cell cancer or adenocarcinoma of the head and neck, colorectal cancer, renal cancer, brain cancer, small and non-small cell lung cancer, bladder cancer, bone or joint cancer, uterine cancer, cervical cancer, multiple myeloma, hematopoietic malignancies, lymphoma, Hodgkin's disease, non-Hodgkin's lymphoma, skin cancer, melanoma, squamous cell carcinoma, leukemia, lung cancer, ovarian cancer, stomach cancer, Kaposi's sarcoma, laryngeal cancer, endocrine carcinomas, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the pituitary gland, cancer of the adrenal gland, and combinations thereof.
19. The method of claim 17 , wherein the neoplasia is chemo-resistant ER/GR+ breast cancer.
20. The method of claim 17 wherein said neoplasia treating therapy is radiation therapy administered as external beam radiation or teletherapy, wherein the radiation is directed from a remote source.
21. The method of claim 17 wherein said neoplasia treating therapy is radiation therapy administered as internal therapy or brachytherapy wherein a radioactive source is placed inside the body close to cancer stem cells, cancer cells, and/or a tumor mass.
22. The method of claim 17 wherein the method comprises administration of a neoplasia treating therapy followed by the administration of the GCR antagonist ORG34517.
23. The method of claim 17 wherein the method comprises administration of a neoplasia treating therapy and the administration of the GCR antagonist ORG34517 concurrently.
24. The method of claim 17 wherein the method comprises administration of the GCR antagonist ORG34517 followed by the administration of the neoplasia treating therapy.
25. The method of claim 17 wherein said neoplasia treating therapy comprises both radiation therapy and an additional neoplasia treating therapy.
26. The method of claim 17 wherein said additional neoplasia treating therapy is selected from the group consisting of peptides, polypeptides, fusion proteins, nucleic acid molecules, small molecules, mimetic agents, synthetic drugs, inorganic molecules, organic molecules, hormonal therapies, anti-angiogenesis therapies, targeted therapies, biological therapies, immunotherapy, and surgery.
27. The method of claim 17 , wherein the neoplasia expresses multidrug resistance genes when GR is activated through binding by endogenous cortisol.
28. The method of claim 17 , wherein the ORG 34517 given systemically through oral or intravenous routes.
29. The method of claim 17 , wherein the ORG 34517 is given to accomplish cure or remission of tumor.
30. The method of claim 17 , wherein the ORG 34517 is given to accomplish reduction of tumor burden to enhance effectiveness of subsequent surgical resection.