RRM1 (Ribonucleotide Reductase Catalytic Subunit M1)

Structural modeling of a representative complex revealed that PTM-mimic peptides adopt a slightly shifted backbone orientation and altered side-chain positioning, leading to a larger peptide-DR3 interaction interface. These findings provide new insights into the role of PTMs in shaping the immunogenicity of SjD-associated autoantigens and highlight the potential for PTM-mimic peptides to modulate T cell responses in SjD.

Although Gleevec has been transformative for CML, blast crisis CML remains relatively drug resistant...These data suggest that MSI2-HOXA9 acts, at least in part, by increasing expression of the mitochondrial polymerase POLRMT and augmenting mitochondrial function and basal respiration in blast crisis. Collectively, our findings demonstrate for the first time that translocations involving the stem and developmental signal MSI2 can be oncogenic and suggest that MSI, which we found to be a frequent partner for an array of translocations, could also be a driver mutation across solid cancers.

In addition, cutting-edge technologies such as single-cell sequencing and artificial intelligence drug sensitivity prediction provide a new paradigm for precision treatment. In the future, it is necessary to build a "prevention-monitoring-intervention" full-chain management system through dynamic monitoring of multi-omics biomarkers (such as circulating tumor DNA tracking RRM2 amplification) and coordinated intervention of traditional Chinese and Western medicine (such as curcumin reversing drug resistance).

Significantly, combining gemcitabine with NPM1 inhibitor NSC348884 synergistically suppresses CSN6-high pancreatic cancer xenografts. This study characterizes CSN6 as an oncogenic protein that promotes NPM1 stabilization by interacting with DCAF1, thereby enhancing ribosome biogenesis and cellular resistance to gemcitabine in PDAC. NPM1 may serve as a therapeutic target for CSN6 high PDAC that exhibits gemcitabine drug resistance.

Clinically, elevated TFRC and RRM1 expression correlates with poor prognosis, supporting their utility as biomarkers of bladder cancer. Our study identified Bava as the first small-molecule TFRC inhibitor that overcomes gemcitabine resistance through iron modulation, providing both mechanistic insights and a promising therapeutic strategy for bladder cancer.

We also found that the formation of IMP2 oligomeric species, which includes dimers and higher-order oligomers, is sensitive to ionic strength and RNA binding. Our findings provide the first insight into the structural properties of full-length IMP2, which may lead to novel opportunities for disrupting its function.

Finally, the combination of sublethal doses of Actinomycin-D and didox is effective in decreasing cell viability and clonogenicity of RMS cells. Therefore, our data suggests the effectiveness of the RR inhibitor didox on both in vitro and in vivo RMS proliferation.

In this study, we identified that multiple HDAC inhibitors, including fimepinostat, romidepsin and panobinostat, downregulate the levels of the RRM1, RRM2, CHK1, and WEE1 proteins in Ewing sarcoma cells, and impair DNA replication. Additionally, proteomic studies identified that HDAC inhibitors also downregulate the level of the BRD4 protein, a BET bromodomain protein that regulates both the transcriptional program of the EWS::FLI1 oncoprotein and DNA replication. Overall, these results provide novel insight into the molecular mechanisms by which HDAC inhibitors target cancer cells, regulate DNA replication, and inhibit the cellular response to DNA replication stress.

SRSF1 indicated poor prognosis and promoted the progression and cisplatin resistance of BCa cells through the HIF1A/BNIP3/mitophagy axis. It holds significant potential as a novel biomarker for the diagnosis and treatment of BCa, particularly in chemotherapy.

These findings underscore the great potential of BBIT20 as a novel multifaceted anticancer drug candidate for PDAC treatment.

Chemotherapy, TOP2A, HER2, and Ki67 expression were independent predictors of RFS in early-stage IBC patients with HR+. The nomogram we developed using these predictors is a reliable tool for predicting RFS in this patient population.