Molecular hallmarks of renal medullary carcinoma: more to c-MYC than meets the eye

Figures & data

Figure 1. MYC-induced stress responses are renal medullary carcinoma (RMC) hallmarks. The loss of SMARCB1 and gain of 8q promote proteotoxic and replication stress responses mediated by c-MYC. The abundance of copy number alterations (CNAs) can be both a source and a consequence of replication stress which can be therapeutically targeted by agents that further induce replication stress including platinum salts, nucleoside analogs (such as gemcitabine) and topoisomerase inhibitors (such as doxorubicin). Replication stress may also be aggravated by the inhibition of DNA damage repair (DDR) pathways using drugs such as Poly (ADP-ribose) polymerase (PARP) inhibitors or the inhibition of cell cycle checkpoint (CCC) pathways using drugs such as the WEE1 inhibitor adavosertib. MYC-induced proteotoxic stress additionally confers a vulnerability to proteasome inhibitors such as ixazomib.