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TOPI inhibitor-based ADCs may also demonstrate synergy with HIF-1\(\alpha\) inhibitors, given that TOPI is an upstream upregulator of HIF-1\(\alpha\): inhibiting both TOPI and HIF-1 to decrease expression of HIF-1 target genes may reduce prostate tumor progression, increase sensitization to therapy, as well as modulate the tumor microenvironment by reducing immunosuppressive myeloid cells and increasing cytotoxic T cell infiltration 43,44

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