Methods for the treatment of cellular proliferative disorders
The present invention relates to methods of identifying the susceptibility of cells to reovirus infection by measuring constitutive ras-MAP signaling. The invention also pertains to methods using reovirus for the treatment of cellular proliferative disorders, and particularly cellular proliferative disorders wherein the proliferating cells exhibit constitutive MAPK phosphorylation, in mammals. In particular, the methods provide for reovirus treatment of mammals to treat proliferative disorders which include breast tumors, a subset of tumors in which mutation of the ras gene is not believed to play a significant role.
1. A method of determining susceptibility of a cell to reovirus infection by measuring constitutive ras-MAP signaling in said cell, wherein the presence of said constitutive signaling indicates susceptibility to infection by reovirus.
2. The method of claim 1 wherein the ras-MAP signaling is measured by determining the state of phosphorylation of MAP kinase.
3. The method of claim 2 wherein the state of MAP kinase phosphorylation is determined using an antibody specific for phosphorylated MAP kinase.
4. The method of claim 1 wherein the cell is comprised in a biological sample collected from a mammal suspected of having a proliferative disorder.
5. The method of claim 4 wherein the proliferative disorder is neurofibromatosis.
6. The method of claim 4 wherein the proliferative disorder is a solid neoplasm.
7. The method of claim 4 wherein the proliferative disorder is selected from the group consisting of lung cancer, prostate cancer, colorectal cancer, thyroid cancer, renal cancer, adrenal cancer, liver cancer, pancreatic cancer, breast cancer and central and peripheral nervous system cancer.
8. The method of claim 4 wherein the proliferative disorder is breast cancer.
9. The method of claim 4 wherein the mammal is selected from the group consisting of dogs, cats, sheep, goats, cattle, horses, pigs, mice, non-human primates, and humans.
10. The method of claim 4 wherein the mammal is human.