Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition worldwide and a major contributor to cirrhosis and hepatocellular carcinoma (HCC). While metabolic triggers such as obesity and insulin resistance are key drivers of MASLD, growing evidence has identified defects in intracellular quality control-namely impaired autophagy-as central mechanisms governing disease progression. Autophagy, including selective lipophagy and mitophagy, plays a crucial role in hepatic lipid turnover and mitochondrial homeostasis. In MASLD, disruption of these processes contributes to lipid accumulation and oxidative stress, leading to hepatocellular damage (ballooning), fibrogenesis, and HCC. Experimental studies linked impaired autophagic flux to liver injury, and emerging evidence from human genetics suggests that inter-individual inherited variation influences MASLD susceptibility by impairing autophagy. Specifically, main genetic MASLD modifiers such as the p.I148M variant of Patatin-like phospholipase domain-containing protein 3 (PNPLA3) and loss-of-function and hypomorphic variants in autophagy-related gene 7 (ATG7), a core autophagy gene, predispose to ballooning, fibrosis, and HCC. By outlining emerging therapies that restore autophagic flux and reduce steatosis, lipotoxicity, and fibrosis, we propose an integrated precision-medicine model based on genetics and autophagy dynamics biomarkers, offering a new framework for personalized therapeutics.

Skin cancer remains one of the most preventable yet prevalent malignancies worldwide, with non-melanoma and melanoma skin cancers ranking among the top 5 and top 20 most common cancers, respectively. Rising incidence rates in countries such as the United States and Australia have been linked to high ultraviolet (UV) radiation exposure and modifiable behavioral risk factors. Public health efforts increasingly emphasize sun safety education to reduce UV exposure and mitigate long-term cancer risk.

To summarize the current research landscape of intervention strategies for the primary prevention of skin cancer and the study designs used to evaluate these efforts.

We conducted a scoping review following PRISMA-ScR guidelines across PubMed, CINAHL, Embase, Cochrane Library, and PsycInfo. Included studies assessed original sun safety programs implemented in school, community, and healthcare settings, focusing on behavior change, accessibility, and long-term impact.

This review highlights the variability in intervention design and underscores the need for comprehensive, evidence-based strategies that integrate education with accessible resources.

Strengthening these efforts is essential to improving sun safety practices and reducing the global burden of skin cancer.

Chronic and treatment-resistant dermatologic disorders remain difficult to manage with current therapies because of incomplete efficacy, tolerability limitations, and long-term safety concerns. GZ21T is a topical formulation of curcumin, harmine, and isovanillin that has emerged as a potential novel therapy for inflammatory and neoplastic skin disease.

To review the preclinical evidence, proposed mechanism of action, safety data, and future clinical potential of GZ21T in atopic dermatitis, mycosis fungoides, and actinic keratoses.

A focused literature review was performed using published preclinical and early translational studies evaluating GZ17-6.02 and topical GZ21T in dermatologic disease models, including atopic dermatitis, mycosis fungoides, and actinic keratoses. Studies were included if they reported mechanistic, efficacy, or safety outcomes relevant to dermatologic application; non-dermatologic studies were used selectively to contextualize safety and pharmacology.

Across preclinical models, topical GZ21T reduced inflammation, pruritus, lesion burden, and tumor growth while promoting autophagy and suppressing pro-survival signaling pathways including MAPK, PI3K-AKT, mTOR-related pathways, Wnt, and ERBB signaling. In mycosis fungoides models, GZ17-6.02 increased apoptosis and enhanced tumor cell killing, including in combination with standard agents such as bexarotene. Safety data to date suggest favorable local tolerability, minimal systemic absorption in preclinical topical studies, and reversible liver enzyme elevations in oral phase 1 testing of GZ17-6.02.

GZ21T represents a promising topical, multimodal therapeutic approach for inflammatory and premalignant or malignant skin disease. Further clinical studies are needed to confirm efficacy, define long-term safety, and establish its role relative to current standard therapies.

The effect of device type and radiation dose in intraoperative radiotherapy (IORT) for colorectal cancer is not well established. To explore this, we reviewed studies reporting postoperative complications, disease-free survival, local control, and long-term survival in patients treated with non-implantable IORT techniques-IOERT, KV-IORT, and HDR-IORT. Most of the available evidence relates to IOERT or HDR-IORT, which is usually delivered at 15 Gy (range 10-20 Gy). The median dose for KV-IORT is typically 12.5 Gy.

We conducted a systematic search of literature through November 2023 to identify studies that compared non-implantable IORT with surgery alone or other treatment approaches (PROSPERO registration: CRD42024508349). Twenty-five studies involving 2664 patients met the inclusion criteria.

Patients treated with non-implantable IORT tended to achieve better 5-year overall survival than those managed without it, with IOERT contributing most clearly to this difference. A similar pattern emerged for long-term local control, where IORT showed an advantage [OR 2.08, 95% CI 1.19-3.64]; studies of IOERT reported an even stronger effect [OR 2.23, 95% CI 1.07-4.65]. Importantly, the use of IORT did not correspond with higher rates of key postoperative complications, including anastomotic leakage, pelvic collections, wound problems, or bowel obstruction.

Our results suggest that IORT may improve survival and local control for patients with advanced or recurrent colorectal cancer, despite the heterogeneity among studies. Device-related and dose-related factors may also play a role and merit closer study, thus warranting closer examination in future work.

Radioactive iodine (RAI) therapy is often administered post-total thyroidectomy in patients with low-risk differentiated thyroid carcinoma, despite guidelines advising against its routine application. Evidence regarding the efficacy of RAI in reducing recurrence and improving survival in low-risk differentiated thyroid cancer (DTC) remains inconsistent.

We conducted a systematic review and meta-analysis of observational studies and randomized clinical trials that compare RAI versus no RAI in low-risk DTC patients. Databases such as MEDLINE, Scopus, Cochrane Library, and Google Scholar were searched through December 2025. Outcomes included recurrence, recurrence-free survival, treatment response, biochemical markers, and side effects. We performed statistical analysis using Review Manager (RevMan) 5.4 with a random-effects model, reporting odds ratios (OR) with 95% confidence intervals, and significance set at p < 0.05. Heterogeneity was assessed using I² statistics.

Ten studies (n = 5260) were included in the analysis. No statistically significant difference was observed between the two groups for recurrence (OR 0.66, 95% CI: 0.41-1.08; p = 0.10), 5-year recurrence-free survival (OR 2.47, 95% CI: 0.63-9.62; p = 0.19), or treatment response (excellent response: OR 1.00, 95% CI: 0.52-1.92; p = 1.00). Secondary outcomes, including serum thyroglobulin > 1 ng/mL (OR 1.20, 95% CI: 0.00-342.55; p = 0.95), elevated thyroglobulin antibodies (OR 0.91, 95% CI: 0.38-2.16; p = 0.83), xerostomia (OR 5.63, 95% CI: 0.05-667.24; p = 0.48), and dysphonia (OR 0.96, 95% CI: 0.53-1.72; p = 0.88), were also not significantly different between groups, although estimates were not precise.

The available randomized and observational evidence does not demonstrate a clear, clinically meaningful benefit of routine RAI ablation in patients classified as low-risk DTC. These findings should be interpreted with caution due to heterogeneity across studies, variability in outcome definitions, and the predominance of observational data.

Insulin resistance (IR) is involved in the development, progression, and treatment resistance of cancer. Apart from contributing to obesity and type 2 diabetes, IR leads to hyperinsulinemia, disruption of insulin-like growth factor signaling, chronic inflammation, and metabolic remodeling, which fosters a pro-tumorigenic milieu. These changes stimulate the PI3K-Akt-mTOR, MAPK, JAK-STAT, and NF-κB pathways, which increase proliferation, survival, angiogenesis, immune escape, and metastasis. IR also modifies the tumor microenvironment (TME) and dampens anti-tumor immunity. IGF-1R, IL-6, IL-1β, TNF-α, PD-1, PD-L1, and CTLA-4 monoclonal antibodies could be beneficial by inhibiting inflammatory and oncogenic pathways and reinitiating immune surveillance. Tumor resistance and heterogeneity are significant obstacles. This is a structured narrative review of the molecular connections, antibody treatments, translational obstacles, and future refined approaches in oncology.

DNA double-strand breaks (DSBs) are the most severe DNA damage, and defective repair can lead to apoptosis or malignant transformation. DSBs are mainly repaired by nonhomologous end joining (NHEJ) and homologous recombination (HR), while microhomology-mediated end joining (MMEJ) serves as a backup pathway. Since DNA polymerase theta (Polθ) is essential for MMEJ, this pathway is also named Polθ-mediated end joining. Polθ is barely expressed in normal tissues but overexpressed in many cancers, making it a promising therapeutic target. In recent years, Polθ inhibitors and related therapeutic strategies have emerged rapidly, with clinical trials underway. This review summarizes the structure, function and expression of Polθ in tumorigenesis, highlights synthetic lethal strategies, drug development and clinical translation, and discusses current limitations and future directions for cancer research.

Fc-gamma receptors (FcγRs) regulate IgG antibody activity, and Fc-engineering is a proven method to improve the efficacy of tumor-targeting antibodies. Here, we explore tailored FcγR blockade to enhance the therapeutic efficacy and tolerability of immune checkpoint-blocking (ICB) antibodies.

Mechanistically matched murine surrogate and human lead FcγR-blocking and immune checkpoint-blocking antibodies were used to study whether tailored FcγR-blockade, targeting FcγRIIB selectively or all FcγRs, can enhance the efficacy and overcome resistance to immune checkpoint therapy in vivo and in vitro. Mechanistic studies were performed with clinical reagents, including ipilimumab, nivolumab, pembrolizumab, and human FcγRIIB-selective (BI-1607) and pan-FcγR-blocking (BI-1206) antibodies, using human cells and transgenic animals with clinically relevant expression of immune checkpoint receptors.

We demonstrate that FcγRIIB-selective and pan-FcγR-blocking antibodies increase the in vivo efficacy of αCTLA-4 and αPD-1 antibodies, respectively. FcγRIIB-selective antibody enhancement of αCTLA-4 was associated with increased intratumoral Treg depletion, myeloid reprogramming, interferon-γ and CXCL10-induction, and increased activated effector CD8⁺ T cells, correlating with higher activating-to-inhibitory (A:I) FcγR engagement ratios. Conversely, pan-FcγR blockade protected αPD-1-coated T cells from macrophage phagocytosis, increasing intratumoral activated CD8⁺ T cells by decreasing activating and inhibitory FcγRs.

Our studies provide in vivo proof of concept that tailored FcγR blockade enhances immune checkpoint therapy and overcomes resistance through mechanistically distinct pathways. Clinical trials with tailored human FcγRIIB-blocking antibodies are ongoing.

CD3-bispecific antibodies (CD3-BsAbs) represent an emerging modality with promising anticancer potential. Despite increasing regulatory approvals, the development of CD3-BsAbs remains challenging. CD3-BsAb candidates are routinely assessed and compared via in vitro workflows. However, protocol heterogeneity across experimental laboratories constrains cross-study potency comparisons. To address this, we developed an in vitro Quantitative System Pharmacology (QSP) model that mechanistically characterizes key processes underlying CD3-BsAb activity. The aim was to establish a framework adaptable to diverse in vitro conditions. The current framework comprises (a) single-cell trimer formation sub-model, (b) trimer-mediated T-cell activation and differentiation sub-model, (c) effector T-cell mediated tumor cell killing sub-model. We evaluated the framework using DuoBody-CD3x5T4 (CD3 equilibrium dissociation constant (K_D) = 683 nM) data from 14 solid tumor cell lines spanning 5T4 expression of 9,447-61,686 molecules/cell and drug concentrations of 1.76E-05-42.8 nM. For a subset of cell lines, we also included additional data comparing DuoBody-CD3x5T4 with bsIgG1-CD3x5T4 (CD3 K_D = 16 nM) and assessing effector-to-target (E:T) ratios of 1:1-8:1. All in vitro data were pooled into a single modeling dataset. A joint fit of T-cell activation and tumor cell cytotoxicity across the interconnected sub-models accurately captured the data and demonstrated mechanistic consistency. The model yielded mechanistically meaningful parameters, such as the per-T cell trimer count required to achieve half-maximal T-cell activation (EC50_act, estimated to be 2.12-4.6 trimers/T cell). The model's mechanistic structure and versatility suggest its potential to serve as a platform to predict drug effects across diverse assay conditions, quantify assay-dependent effects, and guide candidate selection.

Oral malignant melanoma (OMM) is a rare and aggressive malignancy, and involvement of the tongue is particularly uncommon. We report a case presenting with two isolated pigmented tongue lesions clinically resembling benign conditions. Excisional biopsy of the anterior lesion confirmed melanoma, and the tongue base lesion was clinically suspected to represent possible in-transit metastasis. To our knowledge, in-transit metastasis in OMM is not well documented. The patient underwent wide local excision followed by adjuvant pembrolizumab based on cutaneous melanoma guidelines. Final pathological staging was pT3b pN1c cM0 (stage IIIC). At 1-year follow-up, no recurrence or metastasis was observed and oral function was preserved with a palatal augmentation prosthesis. This case highlights diagnostic challenges and the importance of early biopsy and multidisciplinary management. Additional cases and further multicentre studies are needed to validate these observations and guide the development of standardised treatment protocols in the diagnosis and management of OMM.