TACC3 (Transforming acidic coiled-coil containing protein 3)

Thus, FOXM1 reshapes the TACC3-KAT2A interaction, while DNMT1 drives context-dependent DNA methylation, activating the CDK1-inhibitory kinase PKMYT1. We uncovered TACC3-KAT2A as an emerging regulatory axis caused by alternative splicing in HCC and propose FOXM1-driven TACC3 inhibition to synergistically disrupt mitotic fidelity and transcriptional regulation, potentially offering new therapeutic avenues for HCC with reduced toxicity to the normal liver.

Approximately 9% of GBMs harbor targetable fusions, with five genes (FGFR3, MET, EGFR, NTRK2, PDGFRA) comprising 8%. These findings support multi-arm clinical trials to evaluate targeted therapies, potentially improving outcomes for molecularly defined GBM subgroups.

Pharmacologically, dedicated inhibitors like Infigratinib have demonstrated anti-tumor activity in clinical Phase II trials for FGFR-altered recurrent gliomas, while the multi-kinase inhibitor Regorafenib has shown a modest survival benefit in recurrent GBM; however, mechanistic studies indicate that effective response often relies on co-targeting bypass pathways (e.g., CLK2) and mitigating the tumor's metabolic dependency. Crucially, limited drug exposure through the blood-brain barrier (BBB) continues to be the foremost challenge, dictating optimization efforts toward compounds with favorable pharmacokinetic properties and novel delivery platforms, such as the covalent inhibitor futibatinib and liposomal formulations, to enhance brain penetrance. In conclusion, the evolving molecular landscape validates FGFR alterations as a targetable niche in gliomas, and future success depends critically on integrating comprehensive next-generation sequencing to identify aggressive FGFR variants, developing next-generation inhibitors with superior BBB permeability, and implementing rational combination strategies to achieve durable clinical benefit.

In conclusion, a subset of CKD-/ESRD-associated iCCAs in Taiwan shows molecular and chemical evidence of AA exposure. However, the modest correlation between AA adducts and SBS22a signatures and the paucity of T>A transversions in driver genes suggests that AA acts as a contributory rather than causal factor, possibly synergizing with aging and liver disease-related mutagenic processes.

Only the combination of an Fgfr3 E18 truncation with a RE partner gene that encodes a receptor-dimerizing domain resulted in the development of tumors, which were sensitive to FGFR inhibition. Overall, these findings suggest that patients with cancers that are positive for rearranged FGFR3 resulting in E18 truncation and a fusion to dimerizing partners should be considered for FGFR-targeted therapies.

NGS represents the most suitable approach in molecular profiling of FGFR aberrant transcripts. Rings trial based on artificial reference samples play a pivotal role in optimizing routine diagnostic procedures filling the gap in clinical stratification of iCCA patients.

The findings highlight their potential as promising therapeutic candidates for targeting FGFR-driven malignancies. Future efforts will focus on further improving stability and optimizing physicochemical properties to advance these compounds toward translational development.

These alterations were mutually exclusive with common drivers such as EGFR or KRAS. Detection of rare fusions highlights the therapeutic potential of comprehensive NGS profiling in Romanian NSCLC patients.

Loss of PRR14L prolongs SAC-dependent mitotic arrest in response to microtubule depolymerization but, paradoxically, leads to catastrophic mitotic errors upon SAC abrogation by MPS1 inhibitors. A model derived from our findings provides a rationale for exploiting MPS1 inhibition as a potential vulnerability in cancers containing either PRR14L loss of function mutations or FGFR-TACC3 fusions.

However, their detailed contributions remain insufficiently characterized and warrant further investigation. This review underscores the role of primary cilia in PCa progression, highlights unresolved mechanistic gaps in their regulation, and proposes future directions for targeted molecular and therapeutic research.

Recently, Khan and colleagues thoroughly characterized a recurrent FGFR3-TACC3 fusion caused by HPV integration in oropharyngeal squamous cell carcinoma (OPSCC) identifying synergistic interplay with HPV E6/E7 required for transformation. These findings reveal another mechanism in which virus integration can ignite tumorigenesis and a promising avenue for future investigation.

Drug sensitivity analysis suggested therapeutic efficacy of Entinostat and 5-fluorouracil in this subgroup. Our study provides the first LLPS-associated prognostic framework for CRC, offering both a risk stratification tool and actionable therapeutic insights. The findings highlight LLPS as a critical molecular organizer in CRC pathogenesis and a potential target for precision oncology approaches.