Choriocarcinoma is a rare but highly aggressive gestational trophoblastic tumor, characterized by early vascular invasion and distant metastasis. While cure rates exceed 90% with chemotherapy, patients with high-risk, bulky, or chemoresistant disease have a poor prognosis. This review explores the repurposing of statins as a novel therapeutic strategy, hypothesizing that their inhibition of the mevalonate pathway critically disrupts the mechanosignaling networks that drive choriocarcinoma invasion and resistance. By depleting geranylgeranyl pyrophosphate (GGPP), statins inactivate Rho family GTPases, master regulators of cytoskeletal dynamics and cellular mechanics. In choriocarcinoma models, this step leads to the collapse of the actin cytoskeleton, abrogation of cell migration, and suppression of matrix metalloproteinase activity. Preclinical studies demonstrate that achievable concentrations of simvastatin and atorvastatin reduce proliferation, trigger apoptosis, lower β-hCG secretion, and inhibit tumor growth and metastasis, even in chemoresistant lines. GGPP, but not cholesterol, reverses these effects, confirming a prenylation-dependent mechanism. To build a translational rationale, we synthesize the epidemiology, risk factors, and pathophysiology of choriocarcinoma with statin pharmacology. The evidence suggests that statins attack a core vulnerability of this malignancy byimpairing mechanotransduction, effectively reprogramming the tumor cell from an invasive to a static state. We argue for early-phase clinical trials of statins in high-risk or refractory choriocarcinoma, positioning them as a promising, low-toxicity adjunct that targets the biomechanical engines of disease progression.

Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and poor prognosis. Coupled with this, TNBC shows a high rate of metastasis which is known to be aided by tumour vasculature. Endothelial cells that form the lining of the tumour vasculature exhibit distinct genotype and phenotype differences compared with normal tissue vasculature. However, little is known about endothelial signatures that drive metastasis from a primary tumour, particularly in the context of immune infiltration. In this study, we utilized GeoMX Digital Spatial Profiling to investigate spatial proteomics differences in endothelial cells between primary and secondary sites of TNBC. By segmenting tissues using epithelial (PanCK), immune (CD45), and endothelial (CD31) markers, we analysed the microvasculature for a panel of 79 target proteins. In paired primary and secondary TNBC tissues, we identified significant downregulation of fibronectin (- log2(Fold-Change) = - 1.7, p < 0.001) in secondary sites. Specifically in epithelial regions, S100B was found to be downregulated in secondary microvasculature when compared to primary tumours. Additionally, metastasis-free primary tissues exhibited upregulated expression of S100B when compared to primary tissues that metastasized. Our study highlights the potential contributions of microvasculature to metastatic progression in TNBC, presenting new opportunities to explore them as potential biomarkers of TNBC metastasis.

By conducting colorectal cancer liver metastases (CRLM) clinical trials and analyzing treatment and prognostic targets, to provide clinical trial references for CRLM. We analyzed global and Chinese CRLM clinical trials from the Informa database, focusing on fruquintinib, sintilimab, and dual immunotherapy (CTLA-4 + PD-1). The study evaluated oncogenic biomarkers and therapeutic targets, assessing their safety by integrating data from Genotype-Tissue Expression (GTEx)-RNA, Human Protein Atlas (HPA)-RNA and HPA-Protein. Target specificity and future potential were further investigated using Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets and HPA pathology. CRLM clinical trials numbers have stabilized, focusing mainly on combination therapies, with China and the US leading in trial numbers. Single-agent trials emphasize targeted therapy, while chemo plus targeted therapy dominates combinations, reflecting a treatment model based on chemotherapy with targeted therapy breakthroughs. Chinese independently developed drugs-fruquintinib and sintilimab-and dual immunotherapy (CTLA-4 + PD-1) are still emerging, with fruquintinib used for CRLM resistant to multi-line chemo and anti-VEGF. The relevance of VEGFA and EGFR targets highlights targeted therapy's importance and supports drugs like fruquintinib. Targets analysis shows most have low safety and specificity, but CD34, FLT1, and TP53 exhibit good profiles and potential for CRLM therapy and prognosis. This study, by integrating and analyzing the clinical trial data related to CRLM, aims to conduct an in-depth investigation and evaluate the safety specificity of the treatment targets through reference.

Kinesin family member 14 (KIF14), a microtubule-associated motor protein, plays a crucial role in cytoskeletal dynamics, intracellular transport, and cell division. Oncological studies have consistently reported KIF14 overexpression across various cancers, including breast, ovarian, lung, liver, and brain tumors, associating it with poor clinical outcomes, increased tumor aggressiveness, and resistance to conventional therapies. This review comprehensively analyzed the involvement of KIF14 in cancer progression, particularly its roles in cell cycle regulation, mitotic spindle formation, and oncogenic signaling pathways. Additionally, the molecular mechanisms underlying its tumorigenic effects, its potential as a prognostic biomarker, and its viability as a therapeutic target are explored. The expanding understanding of KIF14's oncogenic functions present promising opportunities for developing novel therapeutic strategies aimed at this key regulator of tumor growth and metastasis, addressing the urgent need for treatments targeting aggressive and therapy-resistant malignancies.

The specific role of minimal extrathyroidal extension (mETE)-particularly the differences between anterior mETE (ant-mETE) and posterior mETE (post-mETE)-in relation to Central lymph node metastasis (CLNM) for papillary thyroid carcinoma (PTC) remains uncertain. This study aimed to examine the effects of ant-mETE and post-mETE on CLNM and to construct a preoperative risk-stratification nomogram for CLNM to guide central lymph node dissection (CLND). This retrospective study analyzed 1694 consecutive clinically node-negative (cN0) PTC cases treated between 2017 and 2024. Univariate and multivariate analyses were performed to identify clinicopathological predictors of CLNM. Subsequently, a predictive nomogram incorporating significant variables was developed and internally validated. Among 1694 cN0 PTC cases analyzed, 833 (49.2%) demonstrated pathologic CLNM, and post-mETE was significantly associated with higher CLNM rates compared to ant-mETE (p < 0.001). Multivariable analysis identified seven independent CLNM predictors: age > 55 years (OR 0.466), male gender (OR 2.479), tumor size > 1 cm (OR 3.290), bilateral involvement (OR 1.335), multifocality (OR 1.420), lower pole location (OR 1.710), and mETE presence (ant-mETE OR = 2.47, post-mETE OR = 3.492). The developed nomogram demonstrated excellent discriminative ability (AUC = 0.774) and clinical utility. Both ant-mETE and post-mETE were independently associated with CLNM, with post-mETE demonstrating significantly higher metastatic propensity. The predictive nomogram developed in this study demonstrated moderate discriminative accuracy for CLNM, which could help identify occult metastases, thereby facilitating prophylactic CLND and reducing reoperation rates in patients.