p160 nuclear receptor coactivator family members and their role in rare fusion-driven neoplasms (Review)

Gene fusions with translocations involving nuclear receptor coactivators (NCoAs) are relatively common among fusion-driven malignancies. NCoAs are essential mediators of environmental cues and can modulate the transcription of downstream target genes upon binding to activated nuclear receptors. Therefore, fusion proteins containing NCoAs can become strong oncogenic drivers, affecting the cell transcriptional profile. These tumors show a strong dependency on the fusion oncogene; therefore, the direct pharmacological targeting of the fusion protein becomes an attractive strategy for therapy. Currently, different combinations of chemotherapy regimens are used to treat a variety of NCoA-fusion-driven tumors, but given the frequent tumor reoccurrence, more efficient treatment strategies are needed. Specific approaches directed towards inhibition or silencing of the fusion gene need to be developed while minimizing the interference with the original genes. This review highlights the relevant literature describing the normal function and structure of NCoAs and their oncogenic activity in NCoA-gene fusion-driven cancers, and explores potential strategies that could be effective in targeting these fusions.