Category

Archives

Methylation

Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma

1 | Oct 16 2019

AbuHammad S et al. provided a strong rationale for further investigation of novel combinations of CDK4/6 and PRMT5 inhibitors, not only in melanoma but other tumor types, including breast, pancreatic, and esophageal carcinoma. [Read the Full Post]

Blocking EZH2 methylation transferase activity by GSK126 decreases stem cell-like myeloma cells

0 | Aug 27 2019

Zeng D et al. suggested that EZH2 inactivation by GSK126 is effective in killing MM cells and CSCs as a single agent or in combination with bortezomib. Clinical trial of GSK126in patients with MM may be warranted. [Read the Full Post]

Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma

25 | Aug 19 2019

Knutson SK et al. indicated these data confirm the dependency of EZH2-mutant NHL on EZH2 activity and portend the utility of EPZ-6438 as a potential treatment for these genetically defined cancers. [Read the Full Post]

A patent review of arginine methyltransferase inhibitors (2010-2018)

37 | Jul 10 2019

Li X et al. summarized the updated patented inhibitors targeting PRMTs from 2010 to 2018. The authors illustrate the chemical structures, molecular mechanism of action, pharmacological activities as well as the potential clinical application including combination therapy and biomarker-guided therapy. PRMT inhibitors in clinical trials are also highlighted. The authors provide a future perspective for further development of potent and selective PRMT inhibitors. [Read the Full Post]

Inhibition of G9a by a small molecule inhibitor, UNC0642, induces apoptosis of human bladder cancer cells

48 | Jun 26 2019

Cao YP et al. demonstrated that G9a may be a promising therapeutic target for UBC, and an epigenetics-based therapy by UNC0642 is suggested. [Read the Full Post]

Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin

75 | Jun 06 2019

Wang Q et al. suggested that elevating H3K27me3 level can improve drug sensitivity in CRC patients. [Read the Full Post]

Menin regulates the serine biosynthetic pathway in Ewing sarcoma

98 | May 09 2019

Svoboda LK et al. demonstrated that the SSP is highly active in Ewing sarcoma and that its oncogenic activation is maintained, at least in part, by menin-dependent epigenetic mechanisms involving trithorax complexes. [Read the Full Post]

Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN

145 | Mar 10 2019

Jabbour E et al. indicated that treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. [Read the Full Post]

Inhibition of H3K27me3 Histone Demethylase Activity Prevents the Proliferative Regeneration of Zebrafish Lateral Line Neuromasts

127 | Mar 06 2019

Bao B et al. indicated that H3K27me3 demethylation is a key epigenetic regulator in the process of hair cell regeneration in zebrafish and suggest that H3K27me3 histone demethylase activity might be a novel therapeutic target for the treatment of hearing loss. [Read the Full Post]

Inactivation of PBX3 and HOXA9 by down-regulating H3K79 methylation represses NPM1-mutated leukemic cell survival

131 | Feb 27 2019

Zhang W et al. indicated that NPMc+ leukemic cell survival requires upregulation of PBX3 and HOXA9, and this action can be largely attenuated by a DOT1L inhibitor. [Read the Full Post]

Preclinical evaluation of the BET bromodomain inhibitor BAY 1238097 for the treatment of lymphoma

212 | Jan 02 2019

Bernasconi E et al. indicated the use of combination schemes targeting EZH2, mTOR and BTK alongside BET bromodomains. [Read the Full Post]

BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma

203 | Jan 02 2019

Parasramka M et al. showed that NEAT-1 is a downstream effector of gemcitabine sensitivity in CCA. The expression of BAP1 is a determinant of sensitivity to therapeutic drugs that can be exploited to enhance responses through combination strategies. [Read the Full Post]

Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification

206 | Dec 31 2018

Gherardi S et al. suggested therefore that Menin could take an important part to the Ezh2-epigenetic repressive landscape in many cells and tissues through its capacity to modulate Akt phosphorylation. [Read the Full Post]

Epigenetic drug combination induces remission in mouse xenograft models of pediatric acute myeloid leukemia

264 | Nov 18 2018

Gopalakrishnapillai A et al. indicated the expression of mutant p53 in MV4;11 cells reduced sensitivity to azacitidine-panobinostat combination, suggesting that p53 may be a predictor of response to epigenetic therapy in pediatric AML. [Read the Full Post]

Epigenetic repression of miR-375 is the dominant mechanism for constitutive activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma.

304 | Oct 12 2018

Tatekawa S et al. showed the universal involvement of overlapping epigenetic dysregulation for abnormal miR-375 repression in MM, which is likely to contribute to myelomagenesis and to subsequent myeloma progression by activating oncogenic signalling pathways. [Read the Full Post]

Multi-omics maps of cotton fibre reveal epigenetic basis for staged single-cell differentiation

456 | May 06 2018

Wang M et al. illustrated two divergent pathways mediating a continuous increase of DNA methylation and also sheds further light on the epigenetic basis for single-cell differentiation in plants. [Read the Full Post]