Table 1.
Therapeutic targeting of SE-driven transcription in cancer
| Cancer model | Inhibitor | Effect on SE-driven transcription | Effect of SE inhibition on tumor biology | Ref. |
|---|---|---|---|---|
| DLBCL | JQ1 (BRD4) | Downregulation of SE-driven oncogenic and lineage-specific transcriptional circuits. | Decreased lymphoma infiltration in the bone marrow and improved overall survival | [29] |
| AML | JQ1 (BRD4) | Eviction of BRD4 and Mediator from select SE regions causing decreased expression of associated genes that are MYB targets and important for leukemogenesis | Impaired proliferation and triggering differentiation of leukemic blasts | [76] |
| Oncogenic Nras expression in mouse liver | iBET (BRD4) | Reduced expression of genes involved in SASP that are driven by SEs. | Decreased clearance of oncogenic senescent cells. | [81] |
| T-ALL, MYCN- amplified NB, SCLC, TNBC | THZ1 (CDK7) | Downregulation of SE-associated and tumor addictive and lineage specific gene expression, MYCN-driven transcriptional amplification | Decreased tumor volumes, growth and increased survival | [20–22, 41, 42] |
| AML | Cortistatin A (CDK8/19) | Upregulation of SE-associated genes linked to tumor suppression and lineage specification. | Reduction in disease progression, leukemic burden, and tumor volume, improved overall survival. | [85] |
| T-ALL | THZ531 (CDK12/13) | Downregulation of DNA damage response and SE-associated genes | Apoptosis | [84] |
| Ewing sarcoma | LEE011 (CDK4/6) | Downregulation of SE-associated ES dependency genes CyclinD1/CDK4 | Cytostasis and delayed growth | [87] |
SE, super-enhancer; DLBCL, diffuse large B-cell lymphoma; AML, acute myeloid leukemia; SASP, senescence-etory phenotype; T-ALL, T-cell acute lymphoblastic leukemia; NB, neuroblastoma;; SCLC, small-cell lung cancer; gative breast cancer; ES, Ewing sarcoma