Ibrutinib has demonstrated inhibition of ErbB/HER tyrosine kinases in preclinical models. This Phase I/II study investigated the safety, efficacy, and immunomodulatory effects of ibrutinib in combination with trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) whose disease had progressed on ado-trastuzumab emtansine therapy. In Phase I, cohorts of three patients received ibrutinib 560 mg or 420 mg by mouth once daily combined with standard dosing of trastuzumab. Phase II enrolled additional patients to assess the primary endpoint of clinical benefit rate (CBR) at 420 mg ibrutinib plus trastuzumab. Flow cytometry and NanoString analyses were performed on peripheral blood mononuclear cells. Overall, 26 patients were enrolled. Patients received a median of three prior regimens containing a HER2-targeted therapy in any setting. The most common treatment-related adverse events were bruising, rash, fatigue, and thrombocytopenia. Four patients (15%) experienced cardiac adverse events, including decreased left ventricular ejection fraction in two patients. The CBR of ibrutinib plus trastuzumab was 19.2% (95% confidence interval: 6.6-39.4). Flow cytometry of T- and natural killer (NK)-cell and myeloid-cell panels showed that treatment statistically significantly decreased T helper 17 (T_H17) and myeloid-derived suppressor cells (MDSC) with no decrease in T helper 2 (T_H2) cells. Ibrutinib plus trastuzumab was well-tolerated but had limited anti-tumor activity in patients with heavily pretreated, HER2-positive MBC (NCT03379428). Trial Registration: Clinicaltrials.gov, NCT03379428.

Goniothalamin (GTN), a natural styryl-lactone from the Goniothalamus genus, has demonstrated cytotoxic properties against a variety of human cancer cell lines with minimal effects on normal cells. Its traditional medicinal use and preliminary preclinical evidence suggest potential as a selective anticancer agent. The purpose of this review is to summarize the preclinical anticancer activity, molecular mechanisms, and therapeutic potential of GTN and its semi-synthetic derivatives across cancer cell lines and animal models. A comprehensive literature search was conducted on the anticancer effects of GTN using databases including PubMed, Scopus, and ScienceDirect. Studies reporting in-vitro cytotoxicity, half-maximal inhibitory concentration (IC50) values, mechanisms of action, synergistic drug effects, and in-vivo antitumor efficacy were included. Data on GTN enantiomers and semisynthetic derivatives were also analyzed. GTN exhibited potent, dose- and time-dependent cytotoxicity in breast, colorectal, hepatoma, leukemia, and other cancer cell lines (IC₅₀ in the low micromolar range), while sparing normal cells. Mechanistically, GTN induced DNA damage, reactive oxygen species (ROS) generation, cell cycle arrest, endoplasmic reticulum stress, apoptosis, autophagy, necroptosis, and anoikis. The anticancer activity of GTN enantiomers appears to be cell-line dependent: although the (R)-enantiomer showed higher potency in several cancer models, the (S)-enantiomer displayed greater activity in selected cancer cell lines. GTN synergized with chemotherapeutics such as paclitaxel, vinblastine, and cisplatin, enhancing apoptosis and reducing cell viability. Semi-synthetic derivatives, including methoxy- and nitro-substituted analogs, demonstrated enhanced potency and selectivity. In animal models, GTN exhibited antitumor activity without detectable toxicity. GTN is a promising natural anticancer agent with multimodal mechanisms of action and selective cytotoxicity. Semisynthetic derivatives further improve its potency and specificity. Further in-vivo studies, bioavailability, and pharmacokinetic investigations are warranted to advance GTN towards clinical application.

Resistance to immune checkpoint blockade substantially limits its clinical efficacy in head and neck squamous cell carcinoma(HNSCC). ZC3H13 is a component of the N6-methyladenosine writer complex, but its roles in HNSCC progression and response to anti-programmed cell death protein 1(anti-PD-1) therapy remain unclear.

The expression and clinical relevance of ZC3H13 were evaluated using clinical cohorts and publicly available transcriptomic datasets. Gain- and loss-of-function experiments were performed to determine the effects of ZC3H13 on the malignant phenotypes of HNSCC cells. An epithelial-specific ZC3H13 conditional knockout mouse model of 4-nitroquinoline-1-oxide-induced oral tumorigenesis was used to assess tumor development and responsiveness to anti-PD-1 therapy. N6-methyladenosine modification, RNA stability and functional rescue assays were conducted to investigate the underlying molecular mechanism.

ZC3H13 was upregulated in HNSCC and was associated with poor prognosis and a limited response to anti-PD-1 treatment. ZC3H13 promoted the proliferation and invasion of HNSCC cells, whereas epithelial-specific ablation of ZC3H13 suppressed oral tumorigenesis and enhanced the therapeutic efficacy of anti-PD-1 treatment. Mechanistically, ZC3H13 regulated the N6-methyladenosine modification of cyclin D1(CCND1) mRNA and promoted its IGF2BP1-dependent stabilization, thereby contributing to malignant tumor phenotypes and alterations in immunosuppressvie features.

The ZC3H13/IGF2BP1/CCND1 regulatory axis contributes to HNSCC progression and resistance to anti-PD-1 therapy. These findings identify ZC3H13 as a potential therapeutic target for improving the efficacy of anti-PD-1 treatment in HNSCC.

Gastrointestinal (GI) cancers are a leading cause of cancer-related death worldwide, while drug resistance and treatment-related toxicity continue to limit therapeutic efficacy. A growing body of evidence indicates that the gut microbiota-immune axis (GMIA) is closely involved in the development, progression, and treatment response of GI malignancies. In this review, we summarize current understanding of how gut microbial dysbiosis and GMIA dysfunction contribute to GI cancer development and progression. We highlight the role of natural polysaccharides in modulating gut microbial composition and microbial metabolites, thereby influencing host immune responses and exerting antitumor potential in preclinical settings. In addition, we review recent advances in representative natural polysaccharides as promising candidates for the prevention and treatment of gastrointestinal cancers, with an emphasis on their translational prospects and priorities for future investigation.

Adenocarcinomas originating at stoma sites are extremely rare. While many cases are associated with colorectal cancer or inflammatory bowel disease, instances without such predisposing factors are even rarer.

A 39-year-old man with a history of Hirschsprung's disease presented with tumor growth at his permanent stoma site, which had been established 27 years earlier. A biopsy confirmed adenocarcinoma. Preoperative imaging, including CT, MRI, and PET-CT, showed no evidence of lymph node or distant metastasis. Immunohistochemical staining (CK7+, CK20+, CDX2+) was consistent with a primary tumor of the small bowel. Based on the preoperative diagnosis of localized disease and the clinical goal of preserving intestinal function, local resection was performed with negative margins. Histopathological examination confirmed a primary ileal adenocarcinoma. The patient remains recurrence-free 30 months postoperatively without adjuvant chemotherapy.

This report presents a rare case of stoma-site adenocarcinoma arising 27 years after surgery for Hirschsprung's disease. In long-term survivors of pediatric stoma surgery, chronic physical and chemical irritation may contribute to malignancy even in the absence of a predisposing malignant background. Malignancy at the stoma site can be discovered by patients through self-examination; therefore, both patients and clinicians must recognize the potential risk for early detection.

It is estimated that 5%-10% of patients who develop breast cancer have a causative inherited pathogenic or likely pathogenic variant (P/LP variant). In 2020, the UK National Test Directory published criteria for mainstream genetic testing for breast cancer patients (R208) and, subsequently, eligibility criteria to determine which patients are eligible for gene testing and PARP inhibitor treatment (R444.1).

Using the clearly defined criteria from NHS genomics, eligibility for testing under R208/R444.1 was determined for all patients diagnosed with breast cancer between March 2021 and March 2025. Eligible patients were offered genetic testing. Incidence of P/LP variants and impact on treatment were examined.

A total of 1812 patients had new DCIS/invasive breast cancer diagnoses, 255 were eligible for testing and 196 consented. Of these, 28 patients (14.3%) had a P/LP variant. Eight of these patients were eligible only using family history criteria. Twenty-one patients were eligible for breast conservation surgery. Preoperative genetic results were available for 13: eight patients opted for bilateral mastectomy rather than breast conservation. Where results were available postoperatively, three of eight patients who had breast conservation are planning bilateral risk reducing surgery. Three women newly diagnosed with a BRCA variant received a PARP inhibitor. Eligibility assessment for testing was time-consuming for trained clinicians.

14.3% of patients eligible and tested for a breast cancer-related hereditary P/LP variant were positive, which aligns with the expected number predicted by Genomics England. Family history scoring is an important element. Positive results were associated with changes in surgical decision-making for 14 women and enabled 3 patients to receive a PARP inhibitor.

Radiation therapy (RT) is a mainstay of treatment for a myriad of cancers, often utilized for tumors that are unable to be resected, as well as an adjunct to surgery and chemotherapy. Unfortunately, many cancers are resistant to RT-induced damage and subsequent cell death. This has spurred the pursuit of novel radiation sensitizers that could potentiate the effects of this widely used and important treatment modality. Since its discovery as a regulated cell death mechanism in 2012, ferroptosis has been studied for its connection to cancer and other known oxidative pathways. With this, the interplay between RT and ferroptosis in cancer has recently begun to be explored. Radiation increases reactive oxygen species (ROS), facilitates lipid peroxidation, and releases free ferrous iron, all of which directly impact the ferroptotic pathway. In conjunction, RT has been shown to induce the expression of ferroptosis-related molecules (e.g., SLC7A11, GPX4) through the P62-KEAP1-NRF2 pathway, thereby preventing cell death via ferroptosis. The use of ferroptosis inducers (FINs) to block these antioxidant mechanisms is a promising area of study as pharmacological radiosensitizers to improve the efficacy of RT and patient outcomes. In this comprehensive narrative review, the molecular connections between ferroptosis, cancer, and radiation will be discussed, the preponderance of existing literature investigating the potential of FINs as radiosensitizers will be presented, and possible areas of future study will be offered.

Driven by changes in lifestyle and environmental factors, the global incidence of cancer is steadily increasing, which has established it as a leading cause of mortality worldwide. The current paradigm for cancer diagnosis and treatment relies on conventional methods, such as imaging, endoscopy, and tissue biopsy, which present significant limitations regarding sensitivity in early screening, diagnostic specificity, and personalized treatment. Consequently, the development of more efficient and accurate technologies remains a major objective in modern oncology research, and artificial intelligence (AI) has emerged as a particularly promising solution. Through machine learning and deep learning algorithms, AI is reshaping cancer care by enabling automated detection of minute lesions during screening and quantitative analysis of pathological features for diagnosis. It may also advance tumor theranostics through multimodal data integration for treatment stratification, response prediction, and image-guided or targeted therapeutic decision-making, whereas providing data-driven recommendations for personalized treatment. Despite these prospects, medical AI development faces several key issues, including data bias, model explainability, clinical reliability and generalizability, emerging limitations of foundation models and generative AI, and regulatory and ethical issues that need to be addressed. By reviewing recent advances in AI across screening, diagnosis, theranostics, and treatment, we aim to clarify where these methods are already useful, where evidence remains limited, and why closer collaboration among clinicians, engineers, and data scientists is needed for clinical translation. We hope this review serves as a practical reference for researchers and clinicians evaluating how AI may be integrated into oncology in a more standardized, clinically responsible way.

Pathological diagnosis of colorectal malignant polyps is a core component guiding clinical treatment and subsequent management. Precise diagnosis and risk stratification of malignant polyps by pathologists serve as the fundamental basis for clinicians to formulate individualized treatment plans (including endoscopic resection or additional surgical resection). Accordingly, this article systematically elaborates on the key diagnostic points for malignant polyps, including the Paris endoscopic classification of colorectal polyps and its clinical significance, the histological definition of malignant polyps, assessment systems for submucosal invasion depth (such as Haggitt grading and Kikuchi SM grading), as well as the interpretation of critical high-risk histological features including poor differentiation, lymphovascular invasion, and tumor budding. In addition, diagnostic and differential diagnostic points for special lesion types, such as poorly differentiated intramucosal carcinoma and composite adenoma with microcarcinoid, are also summarized. Collectively, this review aims to provide comprehensive references for pathologists and clinicians, thereby promoting standardized management of colorectal malignant polyps.

Objective: To explore the gross morphology and variation characteristics of the left gastric vein (LGV) by means of cadaveric anatomical measurement and three-dimensional imaging reconstruction. Methods: A total of 39 adult cadaver specimens fixed with 4% formaldehyde solution from Zhongshan School of Medicine, Sun Yat-sen University, and 40 cases of abdominal contrast-enhanced CT imaging data of patients with gastric cancer admitted to the Seventh Affiliated Hospital of Sun Yat-sen University between January 2023 and December 2024 were included in this study. Specimens with obvious decomposition, tissue deformation, structural damage, or a history of upper abdominal surgery were excluded; patients with pathologically confirmed gastric cancer and CT images suitable for three-dimensional vascular reconstruction were selected, while those complicated with liver cirrhosis, portal hypertension, or a history of major upper abdominal surgery were excluded. The perigastric and perihepatic vessels were exposed in cadaver specimens to observe the morphology and course of the LGV and measure related anatomical parameters; the imaging data were scanned with dual-source CT using standardized parameters, and three-dimensional vascular reconstruction was performed on a post-processing workstation. The LGV was classified according to the Lee criteria. Results: Cadaveric dissection showed that the LGV originated from the middle of the lesser curvature of the stomach, coursed leftward along the lesser curvature, received 2-3 esophageal veins at the inferior margin of the esophageal hiatus, and then obliquely descended rightward to drain into the hepatic portal vein. Both cadaveric dissection and imaging detected three drainage sites of the LGV: the hepatic portal vein, the portal vein angle, and the splenic vein. CT angiography (coronal plane) and cadaver specimens both showed that the proportion of drainage into the hepatic portal vein was the highest [52.5% (21/40) vs. 53.8% (21/39)], followed by the splenic vein [35.0% (14/40) vs. 41.0% (16/ 39)], and the least common was drainage into the portal vein angle [12.5% (5/40) vs. 5.1% (2/39)]. The length of the LGV was (40.3±7.4) mm in cadaver specimens and (48.4±11.9) mm on imaging; the distance from the drainage site to the portal vein angle was (13.8±8.1) mm in cadaver specimens and (13.1±8.2) mm on imaging. In both the imaging group and the cadaver group, the type Ip accounted for the highest proportion of LGV classification, at 40.0% (16/40) and 41.0% (16/39), respectively, and no type IV was detected in either group. The proportion of type II in the imaging group was 22.5% (9/40), which was higher than that in the cadaver group (7.7%, 3/39); the proportion of type Ia in the cadaver group was 25.6% (10/39), which was higher than that in the imaging group (15.0%, 6/40); the proportions of type IIIa (20.0% in the imaging group vs. 20.5% in the cadaver group) and type IIIp (2.5% in the imaging group vs. 5.1% in the cadaver group) were similar between the two groups. Conclusions: There are certain variations in the anatomical course and diameter of the LGV. The LGV most commonly drains into the hepatic portal vein, and is mainly classified as type I.