Fig. 8

Mechanism-based combinatorial experimental regimens aimed at disrupting known oncogenic cooperation pathways in GCB-DLBCLs. Targets for rational mechanism-based combinatorial experimental regimens are shown for GCB-DLBCL (a and b). The black thick lines connecting the different drug targets pathways depict established biological interactions and/or dependencies. The single drugs listed in (a) have either proven clinical activity in patients with DLBCL or are currently in clinical trials for patients with B-cell lymphoma, including DLBCL. Pathways in GCB-DLBCL targeted by rational drug combinations using drugs tested as single agent in preclinical studies or clinical trials are shown in (b). Silvestrol inhibits RNA helicase and translation initiationfactor eIF4A thereby blocking translation (i.e., of oncogenic factors) [647]. Azacytidine (AZA) and decitabine/5-aza-2′-deoxycytidine (DAC/5-AZA) inhibit DNA methyltransferases (mainly DMNT1 and DMNT3) resulting in the re-expression of tumor-suppressor genes [419, 420]. Adapted from REF: [601, 602]. Information for this figure was gleaned from the following references: [2, 3, 13, 15–17, 20, 29, 31, 66, 75–84, 87, 93, 107, 123, 148, 233, 255, 257, 324, 325, 352, 354–356, 360–367, 374, 375, 377, 380–382, 384–386, 388, 393, 407, 415–417, 594, 595, 601, 602, 612, 648–650]. See also additional tables 2 and 5–9. Abbreviations: Gα13 (GNA13) heterotrimeric G protein alpha 13, ARHGEF1 Rho guanine nucleotide exchange factor (GEF) 1, PI3K phosphoinositide 3-kinase, mTORC1 mammalian target of rapamycin (mTOR) complex 1, BCL2 B-cell lymphoma protein 2, BCL6 B-cell lymphoma protein 6, EZH2 enhancer of zeste homologue 2, PD-1 programmed cell death, PD-L1 programmed cell death ligand, TGFβR transforming growth factor beta (TGFβ) receptor, HDACi inhibitors of histone deacetylases, BCL6i inhibitors of BCL6, AZA azacytidine, DAC decitabin