Compositions and methods for treating cancer and modulating stress granule formation

摘要

The invention provides methods for treating or decreasing the likelihood of developing a stress-granule related disorder and/or cancer by administering one or more poly-ADP-ribose polymerase (PARP) inhibitors, one or more PARP activators, one or more poly-ADP-ribose glycosylase (PARG) activators, and/or one or more poly-ADP-ribose glycohydrolase ARH3 activators. The invention also provides corresponding methods of decreasing stress granule formation and/or proliferation in a cell or a population of cells. The invention further provides methods of increasing the number of stress granules and proliferation in a cell or a population of cells by administering one or more PARP activators, one or more PARP inhibitors, one or more PARG inhibitors, and/or one or more ARH3 inhibitors. The invention also provides methods for screening for agents for treating or decreasing the likelihood of developing a stress granule-related disorder or cancer, and methods for determining the propensity for developing a stress granule-related disorder or cancer, as well as compositions and kits containing one or more PARP inhibitors, one or more PARP activators, one or more PARG activators, and one or more ARH3 activators.

主权项

1. A method of inhibiting stress granule formation in a subject comprising administering to said subject a therapeutically effective amount of one or more poly-ADP-ribose polymerase (PARP)12 inhibitor(s) and/or one or more PARP13 inhibitor(s) wherein:
(a) said one or more PARP12 inhibitor(s) is (i) an antibody or an antibody fragment that selectively binds PARP12, or (ii) an RNA aptamer comprising the sequence of any one of SEQ ID NOs: 99-106; and/or (b) said one or more PARP13 inhibitor(s) is (i) an antibody or an antibody fragment that selectively binds PARP13.1 and/or PARP13.2, or (ii) an RNA aptamer comprising the sequence of any one of SEQ ID NOs: 40 and 107-113, and wherein said administering results in the inhibition of stress granule formation in said subject.