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Table 2 Regulation of SE activity in chemoresistance

From: Super-enhancers: a new frontier for epigenetic modifiers in cancer chemoresistance

Complex

Cancer

Resistant drugs

Induction methods

SE-associated genes

Mechanisms

References

H3K27ac

Glioblastoma

Temozolomide

50 μM temozolomide

/

Transient resistant state

[183]

Glioblastoma

Temozolomide

/

RFP/HDAC1

Inhibit H3K27ac

[184]

Leukemia

/

/

Notch

Promote H3K27ac

[186, 187]

BRD4

Breast cancer

AKTi

Stepwise method

SirT6, FOXO3a

BRD4/FOXO3a/CDK6 axis

[170]

Melanoma

Vemurafenib

1 μM vemurafenib

YAP/TAZ

Transcription addition mediated by YAP/TAZ through BRD4

[171]

Myeloma

IMiDs

/

PP2A

Hyper pBRD4

[172]

TNBC

BETi

Stepwise method

CK2, PP2A

pBRD4 increase MED1 recruitment

[173]

T cell leukemia

GSI

1 μM GSI

NDME→BDME

Transition from NDME to BDME

[174]

Liposarcoma

Trabectedin

de novo

FUS-DDIT3

Formation of CRC

[175]

PDAC

5-FU

Stepwise method

HMGA2

/

[176]

MCL

Ibrutinib, venetoclax and palbociclib

De novo

E3-ubiquitin ligase

/

[177]

CDK

B cell lymphoma

ABT-199

20 nM ABT-199

BCL2 18q21 loss

Drug-tolerant “persister” state

[191]

Leukemia cells

BETi

/

RNA pol-II, MYC

/

[193]

Anaplastic thyroid carcinoma

Doxorubicin

De novo

DNA damage repair

Downregulation of DNA damage repair

[192]

SEs formation

TNBC

Trametinib

/

RTKs/ERK

SEs de novo formation

[194]

Hepatocellular carcinoma

Sorafenib, cisplatin

5 μM/L sorafenib/cisplatin

Tex10

Formation of ESC related SEs

[195]

ER+ breast cancer

Endocrine therapy

Doxycycline

ER-ligand-independent

Increased combination of ER and SEs

[196]

ER+ breast cancer

Endocrine therapy

Endocrine therapy

Endogenous cholesterol biosynthesis

Epigenetic reprogramming

[197]

  1. TNBC triple-negative breast cancer, PDAC pancreatic ductal adenocarcinoma, MCL mantle cell lymphoma, AKTi AKT inhibitor, IMiDs immunomodulatory drugs, BETi BET bromodomain inhibitors, GSI gamma-secretase inhibitor, NDME notch-dependent MYC enhancer, BDME BRD4-dependent MYC enhancer, RNA pol-II RNA polymerase-II, TSA trichostatin, ESC embryonic stem cell, CRC core transcription regulatory circuitry