The DEBBRAH study showed promising results for patients with HER2-expressing (including HER2-low) metastatic breast cancer who received the antibody-drug conjugate (ADC) trastuzumab deruxtecan for leptomeningeal disease. ADCs represent a novel tool in the precision biomarker-based armamentarium, including in the tumor-agnostic setting, for targeting highly cytotoxic chemotherapy into cancer cells.

The analysis of cell-free DNA (cfDNA) has emerged as a cornerstone of minimally invasive liquid biopsies. We summarize the key advancements of the last five years-deepening insights into fundamental cfDNA biology, innovations in wet- and dry-lab approaches, and the amassment of clinical outcome data-and discuss prospects of this field for the coming half-decade.

Precision medicine has transformed many areas in oncology. However, it remains largely unexplored in metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), where there is a need for further innovative therapies.

To evaluate individual tumor responses to different agents, we have established a standardized personalized drug screening and risk assessment platform utilizing patient-derived GEP-NEN primary cultures (n=23, 16/23 from metastatic tumors, n=12 small intestinal neuroendocrine tumors [siNETs], n=10 pancreatic NETs [pNETs], n=1 neuroendocrine carcinoma [NEC]). We assessed primary culture cell viability, performed signaling pathway analysis by Automated Western blotting and immunohistochemically evaluated tumor composition.

Systematic drug testing of 27 agents including signaling inhibitors (i) (mTORi everolimus, tyrosine kinase inhibitors cabozantinib/sunitinib, AKTi capivasertib, PI3Ki alpelisib, CDK4/6i ribociclib), DNA damage response inhibitors (PARPi niraparib, WEE1i adavosertib, ATRi berzosertib), chemotherapeutics (temozolomide, 5-fluorouracil, lurbinectedin), drug repurposed agents (zoledronic acid) and a personalized risk assessment (GLP-2 analog teduglutide, GLP-1 analog semaglutide, sex hormones) was performed. We demonstrated significant group effects and individualized responsiveness/resistance data. We identified differences in drug response between pNETs/siNETs and between GEP-NETs/GEP-NEC, respectively.

We provide novel data on the efficacy of putative and established therapies in patient-derived GEP-NEN primary cultures. Our standardized platform for personalized drug screening and risk assessment in GEP-NEN primary cultures enables prediction of individual tumor treatment response in this orphan disease.

Canine mammary tumor is the most common tumor in intact female dogs and poses a growing health burden due to its high malignancy rate and increasing canine populations. However, research on sarcomatous subtypes has been hindered by a lack of representative cell lines. Here, we successfully established a novel canine mammary liposarcoma cell line, designated CMLPS-N1, which represents the first such model derived from a spontaneous tumor. This cell line has been stably maintained for over 80 passages and exhibits an abnormal karyotype, high proliferative and migratory capacity, and strong tumorigenicity in mouse xenografts. Molecular profiling confirmed a phenotype consistent with liposarcoma (MDM2+) and mesenchymal origin (Vimentin+/N-cadherin+), alongside high-risk markers (p53+/Ki67+/Notch1), and hormone receptor expression (ER/PR), while being negative for epithelial (PCK) and HER-2 markers. We used functional assays, including cell proliferation, colony formation, wound healing, and transwell invasion, to confirm its aggressive phenotype. Furthermore, cytotoxicity testing with four chemotherapy agents further supports its utility as a preclinical model for therapeutic screening and mechanistic research. The establishment of CMLPS-N1 enriches the canine mammary tumor cell line repository and provides a valuable experimental model for studying disease mechanisms, developing therapies, and facilitating translational applications.

Eukaryotic translation initiation factor 4E (eIF4E) plays a critical role in cap-dependent translation by binding the 7-methylguanosine (m⁷G) cap at the 5' end of mRNAs, thereby regulating the synthesis of proteins essential for cell growth, survival, and proliferation. Under homeostatic conditions, eIF4E selectively translates a subset of mRNAs; however, in cancer, aberrant signaling leads to persistent activation of eIF4E, promoting tumor progression, metastasis, and resistance to therapy. Despite its clinical relevance, very few studies have explored direct targeting of eIF4E's cap-binding function using small molecules as a therapeutic strategy. In the present study, we adopted a multi-layered in silico and experimental pipeline to identify small-molecule inhibitors that can effectively disrupt human eIF4E activity. A library of over 400,000 compounds from the ZINC database was virtually screened using the Glide docking protocol in Schrödinger-Maestro. Compounds were shortlisted based on binding affinity and drug-likeness properties. Among the top hits, ZINC145267992, a nucleoside-like molecule, showed promising interaction with the cap-binding pocket of eIF4E. To overcome potential druggability limitations and improve clinical relevance, Entecavir (ETV), a clinically approved antiviral drug for hepatitis B and a structural analogue of ZINC145267992, was identified as a candidate for drug repurposing. Molecular dynamics simulations confirmed the stable interaction of ETV with eIF4E. Our findings not only reinforce the feasibility of targeting eIF4E in cancer but also demonstrate that repurposing FDA-approved drugs like Entecavir could offer a practical and efficient route to therapeutic intervention. This integrative approach opens new avenues for eIF4E-targeted strategies in oncology, aiming to selectively impair oncogenic translation.

Natural products have acquired prominence in scientific study and medicine owing to their increasing significance in the treatment of human ailments. Manihot esculenta Crantz (cassava) is a fundamental agricultural food crop, widely utilized for its starchy tubers. Cassava leaves are rich in essential components such as calcium, iron, protein, and vitamins A, B, C and K. The leaves have several secondary metabolites, including alkaloids, tannins, and flavonoids, which exhibit anti-inflammatory, antibacterial, anti-diabetic, and immune-modulatory properties. These secondary metabolites may safeguard cells against oxidative stress, chronic diseases, viral ailments, cardiovascular conditions, and specific cancer kinds. These bioactive compounds play a vital role in mitigating oxidative stress, chronic inflammation, and immune dysregulation-key factors implicated in cancer initiation and progression-thus warranting comprehensive investigation of cassava leaves within this framework. Despite their rich phytochemical composition, the nutritional and medicinal significance of cassava leaves remains underexplored. This review aims to summarize the phytochemical constituents of cassava leaves and elucidate their potential health-promoting translational values and anticancer properties. By integrating in vitro, in vivo, and clinical evidence, the review highlights the molecular mechanisms of cassava leaf phytochemicals underlying their anticancer effects and discusses translational implications, existing research gaps, and future directions for experimental and clinical studies.

N6-methyladenosine (m6A) RNA modification plays a pivotal role in gynaecological cancers by regulating tumor initiation, progression, and therapeutic resistance. m6A RNA modification include writers (METTL3/14, RBM15, ZC3H13, WTAP), which catalyze methylation; erasers (ALKBH5, FTO), which remove methyl groups; and readers (YTHDC1, YTHDF1/2/3, IGF2BP1/2/3, HNRNPC/G, HNRNPA2BP1), which interpret m6A marks to regulate the RNA fate. These regulators alter basic RNA metabolism, such as splicing, mRNA stability, translation, and degradation. In gynaecological cancers, both oncogenic and tumor suppressive signaling pathways are also altered by these regulators. Due to their diagnostic, prognostic and predictive value, m6A regulators have emerged as promising biomarkers in gynaecological cancers in recent years. This review highlights the role of m6A regulators and critically evaluates their biomarker and clinical potential in gynaecological cancers.

To evaluate the value of viscoelastic parameters in the differential diagnosis of parotid gland tumors.

A prospective study was conducted on 80 patients with parotid gland tumors who underwent viscoelastic ultrasound examination from September 2024 to April 2025. Patients were divided into four groups: pleomorphic adenoma (PA), warthin tumor (WT), benign tumor (BT), and malignant tumor (MT). Regions of interest (ROI) were delineated within the tumor and a 2 mm surrounding area to measure quantitative parameters, including shear wave elastography (SWE), viscous, dispersion, and strain elastography (SE) parameters. Statistical analysis of the four tumor parameters and qualitative assessment of viscoelasticity maps were performed. The diagnostic performance of each variable in classifying parotid gland tumors was assessed by comparing the area under the curve (AUC).

Parameters such as E-A-mean, Vi-A-max, and Disp-A-mean showed statistically significant differences between PA and WT. Dispersion parameters, including Disp-A-mean, Disp-A-max, and Disp-A-SD, were statistically significant in distinguishing BT from MT and WT from MT. Disp-A-mean had the best diagnostic value, with an optimal threshold of 4.70 m/s/kHz for PA and WT, and 7.08 m/s/kHz for BT and MT, as well as WT and MT. The proportion of Non-Edge Distribution of high dispersion values in the MT group, as shown by the dispersion heatmap, was significantly higher (75%, 9/12) than that in the BT group (14.1%, 10/68) (p < 0.001).

SWE parameters and the Viscous parameter Vi-A-max are useful in differentiating PA from WT. Dispersion parameters can effectively distinguish between PA and WT, WT and MT, and BT and MT. The distribution of the dispersion coefficient can also aid in the differential diagnosis of BT and MT.

QuestionWhat is the role of viscoelastic imaging in differentiating parotid gland tumors? FindingsDispersion parameters can effectively distinguish parotid gland tumors. The distribution of the dispersion coefficient can also aid in the differential diagnosis of BT and MT. Clinical relevanceEffective preoperative differentiation of BT and MT aids in predicting disease progression, selecting surgical options, and assessing prognosis.

Melanoma exhibits significant resistance to conventional apoptosis-based therapies, underscoring the need for alternative strategies to induce cancer cell death. Pyroptosis is a pro-inflammatory form of programmed cell death characterized by caspase-1 activation, gasdermin D cleavage, and interleukin-1β (IL-1β) release. In this study, transcriptomic analysis revealed that aripiprazole induces robust inflammatory signaling in melanoma cells. The antipsychotic drug aripiprazole was found to trigger pyroptosis in BRAF-mutant melanoma cells, leading to caspase-1 activation, gasdermin D cleavage, and increased secretion of pro-inflammatory cytokines. Aripiprazole treatment also activated the MAPK signaling cascade and induced G1 cell-cycle arrest. Notably, aripiprazole rapidly upregulated the expression of nucleotide-binding oligomerization domain-containing protein 2 (NOD2), an innate immune receptor that acts upstream of inflammasome activation and simultaneously regulates MAPK and NF-κB signaling pathways. Genetic and pharmacological evidence demonstrated that NOD2 is essential for aripiprazole-induced pyroptosis and downstream signal propagation. This study provides mechanistic insight into the anti-cancer potential of aripiprazole and supports the broader investigation of serotonergic drugs as immunomodulatory agents in cancer therapy.

Colorectal cancer (CRC), a highly prevalent malignant neoplasm worldwide, poses significant challenges in clinical management due to resistance to radiotherapy and chemotherapy. Notably, chemoresistance in CRC is frequently linked to elevated autophagy levels, prompting extensive exploration of combination therapies that integrate chemotherapeutic agents with autophagy modulators, including both inducers and inhibitors. Moreover, the induction of programmed cell death (PCD) in tumor cells has the potential to improve the therapeutic efficacy of anti-tumor treatments and address key challenges related to drug resistance. Pyroptosis and ferroptosis, two distinct types of PCD, have emerged as potential tumor-suppressive mechanisms owing to their unique molecular characteristics. Increasing evidence supports functional crosstalk between these two processes. Autophagy exerts complex regulatory effects on pyroptosis and ferroptosis through multiple functional subtypes. Growing evidence indicates that various pharmacological agents, small molecules, nanocarrier-based delivery systems, and specific autophagic pathways can selectively induce pyroptosis or ferroptosis. Moreover, combining autophagy modulators with standard radiotherapeutic or chemotherapeutic regimens holds significant promise for enhancing treatment outcomes and restore drug sensitivity in CRC. This review systematically summarizes the molecular mechanisms underlying pyroptosis and ferroptosis along with their roles in CRC pathogenesis, elucidates the central regulatory function of autophagy, discusses innovative strategies leveraging autophagy-mediated activation of pyroptosis and ferroptosis, and evaluates the synergistic potential inherent of integrating autophagy modulation with established treatment modalities. Finally, current challenges pertaining to mechanistic research and clinical translation are critically assessed to provide a robust theoretical foundation for future advances in CRC therapeutics.