Abstract: Disclosed herein are compounds and methods for the inhibition of the RNF1 or RNF2 subunit of polycomb repressive complex 1 (PRC1) for the treatment of metastatic cancer, such as metastatic castration-resistant prostate cancer. The inhibitors can be combined with checkpoint inhibitors such as PD-1 inhibitors, PD-L 1 inhibitors, or CTLA-4 inhibitors.

Abstract: It has now been determined that ?6?4 integrin is a pro-angiogenic receptor, and thus that it provides a novel and heretofore unrecognized target for anti-angiogenic therapy. Thus, angiogenesis, particularly pathological angiogenesis, can be inhibited, and conditions with which pathological angiogenesis is associated treated using inhibitors of ?6?4 integrin. A tissue in which angiogenesis is to be inhibited is exposed to a therapeutic agent effective to reduce the amount of active ?6?4 integrin in the tissue. The tissue may be within a patient, and in particular a human patient to be treated for a disease condition with which pathological angiogenesis is associated. The therapeutic agent may be an antibody or a small molecule, for example a laminin-5 analog, which binds to ?6?4 integrin and inhibits its normal function. The therapeutic agent may also be a chemical species that interferes with the production of ?6?4 integrin, including for example an antisense or RNAi species.