RPS6 (Ribosomal Protein S6)

The findings herein underscore the pivotal role of EV-derived VDAC1 in driving PTX resistance in GC through dual modulation of autophagy and mitophagy, mediated by the AMPK/mTOR signaling axis. Targeting EV-derived VDAC1 has emerged as a promising therapeutic strategy to counteract chemoresistance, providing a novel avenue for improving GC treatment outcomes.

In addition, in vivo xenograft models confirmed that hsa_circ_0003176 overexpression suppressed tumor growth and enhanced DDP sensitivity. Our study reveals the METTL3/m6A/hsa_circ_0003176/RPS6KB1 pathway as a critical pathway in NSCLC chemoresistance, offering novel therapeutic targets for overcoming DDP resistance.

Bufalin has shown potential in overcoming cancer resistance to osimertinib and sorafenib in epidermal growth factor receptor (EGFR)-mutated lung cancer. These effects were more pronounced in the combined intervention group. Bufalin can overcome gefitinib resistance in lung cancer by modulating the EGFR-PI3K/Akt-mTOR signaling pathway.

In vivo validation confirmed that combining RPS6KA2 targeting with autophagy inhibitors or ferroptosis inducers significantly enhanced cisplatin sensitivity in ovarian cancer models. These results collectively indicate that targeting the miR-512-3p/RPS6KA2 regulatory axis may offer a novel and effective strategy for overcoming cisplatin resistance in ovarian cancer.

The potential target genes of activin A receptor type I (Acvr1), ribosomal protein S6 kinase B1 (Rps6kb1), and transforming growth factor beta receptor type 1 (Tgfbr1) were significantly lower in the kidneys of the LPS group. EVs-derived miR-128-3p in LPS induced periodontitis may cause kidney inflammation which may be mediated by, Rps6kb1, Tgfbr1, and Acvr1.

The computational results reveal that kinases like AKT1, ROR1, and ROR2, and non-kinase targets like UBC, RPS6, CDH1, AR, and SMAD3, are the most promising candidates. All screened compounds showed varying strong interacting profiles, with Ellagic Acid and Erioflorin standing out as potent candidates against critical targets in metastatic breast cancer.

Further, RBPs like RPS8, RPL5, RPS3A, EEF1A1, and EIF4E1B were found to be strongly correlated with patients' overall survival. Taken together, our analyses identified several candidate RBPs which might serve as potential targets for oncological measures against gliomas.

We thus provide, for the first time, evidence that HMMR does have oncoprotein-like properties in neuroblastoma cells and that HMMR expression has potential as a prognostic marker. Moreover, initial biochemical analyses highlight a potential influence for HMMR in MTOR and DDR pathway regulation.

Our results show that the multitargeted SRC TKI dasatinib significantly enhanced the efficacy of RET TKIs in RET fusion-positive (RET+) NSCLC and PTC cells...Importantly, synergy was also observed with eCF506 (NXP900), a next-generation clinical SRC inhibitor. Finally, both SRC TKIs restored sensitivity in selpercatinib-resistant RET+ PTC cells. These results elucidate RET and SRC signaling crosstalk in RET+ NSCLC and PTC, suggesting that co-inhibiting SRC has clinical potential in TKI-naïve and -resistant RET+ cancers.

In vivo, the combined treatment of MDL-800 and BYL719 resulted in a prolonged anti-tumor response. Overall, our study identifies the molecular mechanism underlying SIRT6 activation in HNSCC and ESCC and highlights the therapeutic potential of SIRT6 activators, alone or in combination with PI3K inhibitors in cancers where SIRT6 is downregulated or serves as a tumor suppressor.

Targeting these metabolic changes with metformin (a mitochondrial complex I inhibitor) or KPT-9274 (a NAMPT inhibitor) re-sensitized resistant cells to venetoclax. Combination treatments showed strong synergy and near-complete cell elimination. These results highlight metabolic reprogramming as a heterogeneous but targetable resistance mechanism and support combining metabolic inhibitors with BCL2 blockade to treat refractory AML.

We also discuss emerging therapeutic technologies, such as proteolysis-targeting chimaeras (PROTACs) and non-coding RNAs (ncRNAs), which hold promise for future cancer treatments. We aim to offer clearer insights and guidance for developing novel strategies to inhibit eEF2K in cancer therapy, thereby broadening the range of treatment options for patients.