The goal will be to attenuate LEDGF/p75-mediated tumor aggressiveness by using specific small molecule inhibitors (SMIs) of this protein, either alone or in combination with SMIs targeting other members of its transcriptional network (e.g., Menin, MLL1/KMT2A, c-MYC, HRP-2) and standard chemotherapeutic drugs or radiation to circumvent therapy resistance (Figure 4). Here, HDGFL2 is linked to neoplasm.