Abstract: A trigger-responsive immune-inactivating signaling polypeptide disclosed herein can include a modulating domain and an immune-inactivating moiety, such as a dominant negative signaling moiety or constitutively active signaling moiety. A modulating domain can be characterized by an ability to adopt a first state and a second state, and to transition between the first state and the second state when exposed to a trigger. When the modulating domain is in its first state, the immune-inactivating signaling moiety can be inhibited, and when the modulating domain is in its second state, the inhibition can be relieved. Further disclosed herein are compositions for the delivery of a trigger-responsive immune-inactivating signaling polypeptide. Also, methods for using a trigger-responsive immune-inactivating signaling polypeptide, including to regulate an activity of immune system cells, are disclosed.

Abstract: The present disclosure provides methods of treating estrogen receptor-associated diseases, disorders, and conditions.

Abstract: Provided herein are methods of administering estrogen receptor antagonists for use in treatment of cancer. In some embodiments, estrogen receptor antagonists provided herein are tetrahydro pyrido[3,4-b]indole compounds. In some embodiments, provided antagonists are complete estrogen receptor antagonists.

Abstract: Provided herein are methods of administering estrogen receptor antagonists for use in treatment of cancer. In some embodiments, estrogen receptor antagonists provided herein are tetrahydro pyrido[3,4-b] indole compounds. In some embodiments, provided antagonists are complete estrogen receptor antagonists.

Abstract: The present application demonstrates that HDAC inhibitors can be used in combination with hormonal therapy to treat and prevent estrogen receptor positive breast cancer. HDAC inhibitors can also be combined with IGF-1R inhibitors, mTOR inhibitors, and EGFR inhibitors to treat breast cancer, optionally in combination with hormonal therapy if indicated. Combinations of the compounds, with or without HDAC inhibitors, and with or without hormonal therapy, can also be used. The invention therefore provides methods of treatment and pharmaceutical compositions.