MyD88 and Its Inhibitors in Cancer: Prospects and Challenges
Abstract
1. Introduction
2. Biological Structure and Function of MyD88
3. MyD88 Is Associated with Immune Inflammatory Response
4. MyD88 Is Associated with Tumor Progression
4.1. Abnormal MyD88 Signaling Is a Carcinogen
4.2. MyD88 Is Associated with Tumor Cell Proliferation and Metastasis
4.3. MyD88 Is Associated with Tumor Prognosis
4.4. MyD88 Could Be Considered as a Novel Tumor Marker
5. MyD88-Mediated Tumorigenic Pathway
6. MyD88 Is Involved in Tumor Immune Escape
7. Drug Therapy Targeting MyD88
Inhibitor | Structure | Machine | Effect | Year of Publication |
---|---|---|---|---|
MGN1703 | Acts on TLR9/MyD88 signaling pathway | Benefits the treatment of metastatic colorectal cancer [88], enhancing anti-viral immune response to chronic HIV-1 infection [89] | 2015 | |
Tomisetron | Inhibits TLR4/MyD88 signaling | Inhibits the development of colorectal cancer [84] | 2016 | |
Curcumin | Inhibits the expression of TLR4/MyD88 and EGFR in a dose- and time-dependent manner | Inhibits the proliferation and migration of NSCLC [83] | 2019 | |
Mesalazine | Inhibits the TLR4/MyD88-dependent pathway | Resists ulcerative colitis in mice model [76] | 2019 | |
Salvia miltiorrhiza | Compound of traditional Chinese Medicine | Inhibits MD2/TLR4-MyD88 complex formation and signaling | Reduces cardiac dysfunction and inflammatory response in heart failure rats [67] | 2020 |
Radix gentianae | Compound of traditional Chinese Medicine | Inhibits the galectin-3/TLR4/MyD88/NF-κB inflammatory signaling pathway | Prevents acute myocardial infarction induced by isoproterenol in rats [68] | 2020 |
Oxyberberine | Compound of traditional Chinese Medicine | Inhibits the TLR4-MyD88-NF-κB signaling pathway and the translocation of NF-κB p65 from cytoplasm to nucleus | Anti-colitis effect [90] | 2020 |
Dexmedetomidine | Inhibits the TLR4/MyD88/NF-κB signaling pathway | Resists Intestinal Ischemia-Reperfusion Injury [73] | 2021 | |
Rifampicin | Inhibits the TLR4/MyD88/NF-κB signaling pathway | Ameliorates lipopolysaccharide-induced cognitive and motor impairments in mice [77] | 2021 | |
Astragaloside IV | Inhibits the TLR4/MyD88/NF-κB signaling pathway | Prevents acute myocardial infarction [70] | 2021 | |
Icariin | Inhibits the TLR4/MyD88/NF-κB and Wnt/β-catenin signaling pathway | Inhibits the progression of cervical cancer [82] | 2021 | |
Sevoflurane | Inhibits the TLR4/MyD88/TRAF6 signaling pathway | Sevoflurane postconditioning ameliorates cerebral ischemia-reperfusion injury in rats [78] | 2022 | |
Polyene Phosphatidylcholine | — | Acts on TLR2, reduction of the activation of MyD88 IKKs complex | Inhibits the synovial inflammation induced by LPS [81] | 2022 |
Emodin | Inhibits the MyD88/PI3K/Akt/NF-κB signaling pathway | Inhibits the activation of microglia and inflammatory response [79] | 2022 | |
Biogenic AgNPs | — | Targets the TLR4/MyD88 and Nrf2/HO-1 signaling pathways | Inhibits LPS-induced neuroinflammation [71] | 2023 |
Fluoxetine | Attenuates the TLR4/MyD88/NF-κB signaling pathway activation | Alleviates postoperative cognitive dysfunction in aged mice [72] | 2023 | |
Salvianolic acid A | Inhibits TLR2/TLR4-mediated MyD88 activation and its downstream molecules TRAF6 and IRAK4 | Attenuates cardiac inflammation and cardiac disfunction in heart failure mice [80] | 2023 | |
Atorvastatin | Inhibits the TLR4/MyD88/NF-κB signaling pathway | Reduces contrast media-induced proptosis of renal tubular epithelial cells [74] | 2023 | |
Pioglitazone | Attenuates oxidative stress and inflammation via the TLR4/MyD88/NF-κB signaling pathway | Ameliorates cisplatin-induced testicular toxicity [75] | 2023 | |
Xianglian Pill | Compound of traditional Chinese Medicine | Inhibits the TLR4/MyD88/NF-κB signaling pathway | Attenuates ulcerative colitis [69] | 2023 |
Combined treatment with ZA and Tα1 | Structure of ZA | Blocks MyD88/NF-κB signaling in PCa cells and activates the MyD88/NF-κB signaling in macrophages and T cells, leading to increased cytotoxic T cell infiltration and enhanced tumor inflammation | Alleviates the non-immunoreactive patients with advanced or metastatic prostate cancer [85] | 2023 |
Si jun zi tang | Compound of traditional Chinese Medicine | Regulates the TLR4/MyD88/NF-κB signaling pathway and reduces PD-L1 expression | Inhibits the proliferation and migration of lung cancer cells and reduces the expression of PD-L1 protein in A549 cells [86] | 2024 |
Inhibitor | Structure | Machine | Effect | Year of Publication |
---|---|---|---|---|
linear RDVLPGT | — | Inhibits MyD88 dimerization | Inhibits the NF-κB signal pathway [91] | 2008 |
AS-1 | Inhibited the interaction between IL-1R and MyD88 and weakened the binding activity of NF-κB | Protects the myocardium from ischaemia/reperfusion injury [92] | 2009 | |
4210 | Inhibits MyD88 dimerization | Inhibits the pro-inflammatory immune signaling induced by bacterial toxins [107] | 2015 | |
Inhibits the interaction between MyD88 and IRF3/IRF7 and upregulated IFN-α | Anti-viral effect [111] | 2020 | ||
T6167923 | Disrupts the formation of MyD88 homodimer | Protects mice from toxic shock induced by SEB [105] | 2015 | |
Inhibits MyD88 expression | Down-regulates the expression of Col I, Col III, and α-SMA [112] | 2023 | ||
TJ-M2010-5 | Inhibits MyD88 homologous dimerization | Prevents colorectal cancer related to colitis [99], increases the tolerance of allogeneic transplantation in mice [102], prevents DSS-induced acute liver injury in mice [113] and reduces transplant rejection in mice [101] | 2015–2019 | |
Inhibits the MyD88 signaling pathway | Anti-hepatocellular carcinoma [100] | 2019 | ||
Inhibits the TLR7/MyD88/NF-κB and TLR7/MyD88/MAPK signaling pathways | Relieves B cell lupus-like immune disease [103] | 2020 | ||
Inhibits MyD88 homologous dimerization | Reverses myocardial ischemia and reperfusion injury [114] | 2020 | ||
Inhibits the MyD88/NF-κB and Erk pathways Inhibits myeloid cell infiltration and microglia activation | Relieves acute cerebral ischemia-reperfusion injury [115] | 2022 | ||
Inhibits MyD88 homologous dimerization | Alleviates myocardial ischemia/reperfusion injury during heart transplantation [98] | 2022 | ||
Blocks the activation of MyD88/NF-κB | Alleviates liver fibrosis [97] | 2022 | ||
Overcomes the inhibitory function of myeloid suppressor cells | Prevents colorectal cancer development associated with colitis [53] | 2022 | ||
Inhibits cell proptosis | Prevents liver ischemia-reperfusion injury [116] | 2023 | ||
Blocks MyD88 signal transduction | Prevents the development of CAC as well as downregulating GPNMB mRNA [117] | 2023 | ||
ST2825 | Prevents MyD88 from dimerizing | Provides neuroprotection after experimental traumatic brain injury in mice [118], inhibits HCC cell proliferation [94] and relieves lymphoma and leukemia [96] | 2016, 2017 | |
Inhibits the NF-κB signaling pathway Inhibits the production of IL-10 and IFN-β | Relieves B-cell neoplasms driven by activated MyD88 signaling [119] | 2019 | ||
Prevents MyD88 from dimerizing | Prevents synovitis and joint degeneration [120] | 2021 | ||
Inhibits NF-κB activation and the ROS/NLRP3 signaling pathway | Attenuates LPS-stimulated neuroinflammation [121] | 2022 | ||
Prevents MyD88 from dimerizing | Inhibits pancreatic ductal adenocarcinoma [95] and alleviates synovial lesions [122] | 2023 | ||
TJ-M2010-6 | Inhibits MyD88 homologous dimerization | Prevents and cures type 1 diabetes in NOD mice [104] | 2016 | |
TJ-M2010-2 | Inhibits MyD88 homologous dimerization | Offsetting renal ischemia-reperfusion-induced renal injury [123] and alleviates renal interstitial fibrosis [124] | 2016, 2018 | |
Regulates the MyD88/GSK-3β and MyD88/NF-κB signaling pathways | Inhibits the proliferation, migration, and invasion in breast cancer cells [32] | 2020 | ||
Cyclic c (MyD 4-4) | — | Prevents MyD88 from dimerizing | Alleviates immune encephalomyelitis in mice [93] | 2018 |
LM9 | Inhibits the MyD88 and inflammatory pathways in macrophages | Prevents atherosclerosis [125] | 2019 | |
Inhibits the formation of TLR4/MyD88 complexes | Reduces inflammatory response and cardiac fibrosis [106] | 2020 | ||
LM8 | Inhibits the MyD88 Erk/NF-κB-dependent inflammatory pathway | Relieves heart damage [108] | 2020 | |
Inhibits TLR4-MyD88 interaction and NF-κB activation | Protects the kidney from inflammatory damage of diabetes [126], relieves heart inflammation in diabetes mice [127] and relieves hypertensive nephropathy-induced by angiotensin II [128] | 2021, 2022 | ||
M20 | Prevents MyD88 from dimerizing | Reduces sepsis-mediated acute lung injury [109] | 2021 | |
Low temperature oxygenation perfusion combined with TJ-M2010-5 | Inhibits the TLR/MyD88 signaling pathway | Relieves liver ischemia-reperfusion injury [129] | 2022 | |
C17 | Inhibits the interaction between TLR4-MyD88 and NF-κB signaling pathway | Alleviates acute lung injury [110] | 2023 |
8. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CacyBP/SIP | calcycin-binding protein and Siah-1 interaction protein |
CI | confidence interval |
COX-2 | cyclooxygenase 2 |
CX3CL1 | C-X3-C motif chemokine ligand 1 |
DCs | dendritic cells |
DD | death domain |
DLBCL | diffuse large B-cell lymphoma |
EVs | extracellular vehicles |
HGSOC | high-grade serous ovarian cancer |
HMGB1 | High mobility group box-1 protein |
HR | Hazard Ratio |
IDO | Indoleamine-2,3-Dioxygenase |
IFNs | type I interferons |
IFN-γ | interferon-gamma |
IKK | IκB kinase |
IL-10 | interleukin-10 |
IL-18R | interleukin-18 receptor |
IL-1R | interleukin-1 receptor |
IL-6 | interleukin-6 |
iNOS | nitric oxide synthase |
INT | intermediate domain |
IRAK | IL-1R-associated kinase |
IRF-7 | interferon regulatory factor 7 |
LGSOC | low-grade serous ovarian cancer |
MAPK | mitogen-activated protein kinase |
MDSCs | myeloid suppressor cells |
MT1-MMP | membrane type 1 matrix metalloproteinases |
MyD88 | Myeloid differentiation factor 88 |
NF-κB | nuclear factor-κB |
PAUF | pancreatic adenocarcinoma up-regulated factor |
PCa | prostate cancer |
PD-1 | programmed death 1 |
PD-L1 | programmed death ligand 1 |
Ras/ERK | rat sarcoma virus/extracellular signal-regulated kinase |
TAMs | tumor-associated macrophages |
TIR | toll interleukin-1 receptor |
TLRs | toll-like receptors |
TME | tumor microenvironment |
TNF-α | tumor necrosis factor α |
WM | Waldenstrom macroglobulinemia |
WT | wild-type |
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Song, J.; Li, Y.; Wu, K.; Hu, Y.; Fang, L. MyD88 and Its Inhibitors in Cancer: Prospects and Challenges. Biomolecules 2024, 14, 562. https://doi.org/10.3390/biom14050562
Song J, Li Y, Wu K, Hu Y, Fang L. MyD88 and Its Inhibitors in Cancer: Prospects and Challenges. Biomolecules. 2024; 14(5):562. https://doi.org/10.3390/biom14050562
Chicago/Turabian StyleSong, Jiali, Yuying Li, Ke Wu, Yan Hu, and Luo Fang. 2024. "MyD88 and Its Inhibitors in Cancer: Prospects and Challenges" Biomolecules 14, no. 5: 562. https://doi.org/10.3390/biom14050562
APA StyleSong, J., Li, Y., Wu, K., Hu, Y., & Fang, L. (2024). MyD88 and Its Inhibitors in Cancer: Prospects and Challenges. Biomolecules, 14(5), 562. https://doi.org/10.3390/biom14050562