Radiotherapy (RT)-elicited antitumor immunity serves as a pivotal mechanism in RT-mediated tumor control. The strategic integration of RT with immunotherapies, particularly immune checkpoint blockade (ICB), is revolutionizing cancer therapeutics, demonstrating remarkable clinical potential. In this context, identifying molecular targets to potentiate radioimmunotherapy (RIT) efficacy represents a critical research priority. Emerging as a central immunomodulatory axis, the cGAS/STING signaling pathway bridges DNA damage response with antitumor immunity, positioning itself as a prime therapeutic target for radiation sensitization. Our study unveils caspase-activated DNase (CAD) as a previously unrecognized suppressor of cGAS/STING signaling that governs radiosensitivity in colorectal cancer (CRC). CAD physically blocks STING dimerization and cGAMP binding through a nuclease-independent function, thereby compromising RT-induced STING activation and subsequent type I interferon (IFN-I) production. Functional analyses demonstrated that CAD ablation potentiates CD8+ T cell infiltration/activation within the tumor microenvironment and synergizes with anti-PD-1 immunotherapy upon radiation. Translational validation revealed clinical correlations between CAD overexpression in CRC specimens and suboptimal radiotherapy responses coupled with diminished intratumoral CD8+ T cell infiltration. Collectively, our findings establish CAD as a novel rheostat of cGAS-STING signaling and propose CAD inhibition as a promising combinatorial strategy to enhance RT and RIT efficacy in CRC.

IDH-mutant gliomas represent a subtype of diffuse gliomas that primarily affect patients in early to mid-adolescence. These tumors are classified into three distinct CNS WHO grades of malignancy. Accurate grading is essential for selecting an appropriate treatment maximizing anti-tumor efficacy while minimizing adverse effects. However, grading of oligodendrogliomas with 1p/19q codeletion currently relies on qualitative tumor characteristics that may be influenced by observer subjectivity, sampling bias, and tumor heterogeneity. This study aimed to explore DNA methylation-based tumor deconvolution into latent methylation components (LMCs) to evaluate their potential as objective grading tools in a cohort of 137 IDH-mutant gliomas. LMCs were analyzed in relation to malignancy markers, cellular composition, and underlying methylation signatures of the chromatin landscape. Glioma subtypes were associated with distinct LMCs. Two LMCs correlated with higher cellular density and advanced epigenetic age as well as with microvascular proliferation, necrosis, and epigenetically defined high-grade astrocytoma. The epigenetic patterns defining high-grade astrocytoma or oligodendroglioma, respectively, were similar. Higher-grade oligodendrogliomas, identified by LMC-based grading, were associated with more copy number alterations. Among patients of an external cohort who died during the assessment period, higher LMC1 proportions were associated with poorer overall survival. Therefore, LMCs hold the potential to support IDH-mutant glioma grading by incorporating objective epigenetic markers.

Extramedullary involvement (extramedullary disease, EMD) is an aggressive subtype of multiple myeloma (MM) characterized by myeloma subclones proliferating independently of the bone marrow microenvironment, often associated with high-risk cytogenetic abnormalities, immune evasion, and treatment resistance. While significant breakthroughs have been achieved in MM treatment with the sequential approval of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, prognosis remains poor once EMD develops. Even in the era of immunotherapy, the survival benefit for EMD patients has not shown significant improvement. This review systematically summarizes therapeutic options for MM patients with EMD, aiming to provide evidence-based guidance for EMD treatment.

The adaptor protein SRCIN1 is a novel Src-binding protein that regulates Src activation through C-terminal Src kinase. SRCIN1 has been shown to promote the development of colorectal cancer, while acting as a tumor suppressor in breast cancer. However, its role in the development of thyroid cancer has remained unknown. In this study, we analyzed the biological characteristics of SRCIN1 in thyroid cancer using public data (HPA, TIMER, GEPIA and UALCAN). Additionally, we investigated the biological impact of SRCIN1 knockdown and overexpression on thyroid cancer cells both in vitro and in vivo. Our results revealed that the expression of SRCIN1 was higher (more than twice) in thyroid cancer tissues than in normal tissues and was positively correlated with tumor stage (stage1 vs. stage4 p < 0.05). Suppression of SRCIN1 promoted cell apoptosis (at least onefold) and inhibited cell proliferation and migration (at least 50%), whereas overexpression had the opposite effect. Furthermore, our analysis indicated that SRCIN1 activates the Wnt/β-catenin signaling axis, as evidenced by increased levels of β-catenin, DVL2, Cyclin D1, c-Myc, and Axin2. TOP/FOP experiments also revealed that Wnt/β-catenin signaling was activated by SRCIN1. It is noteworthy that the specific knockdown of SRCIN1 results in a reduction of key downstream gene targets within the Wnt/β-catenin axis, and tumors in mice treated with SRCIN1-targeting siRNA exhibit significantly smaller volumes (reduction exceeding 50%). Taken together, our study highlights the clinical and therapeutic relevance of SRCIN1 in thyroid cancer and suggests it as a potential therapeutic target for this disease.

Anti-EGFR monoclonal antibodies are essential for metastatic colorectal cancer (CRC) treatment, however, resistance remains problematic in KRAS/NRAS/BRAF wild-type patients. RAS protein activator-like 2 (RASAL2) regulates RAS signaling by catalyzing the conversion of RAS. This study investigates the pathogenicity of the germline RASAL2 c.2423 A > G variant, identified in a high-risk family, and its potential role in CRC progression and therapy resistance. Population analysis reveals its rarity in East Asians (0.01%) but an increased prevalence in Taiwanese CRC patients (1.63%). Functional studies demonstrate that RASAL2 c.2423 A > G enhances RAS signaling, causing sustained ERK phosphorylation and increased CRC cell proliferation. Additionally, RASAL2-mutant cells require higher doses of cetuximab for ERK suppression and growth inhibition, indicating resistance to anti-EGFR therapy via abnormal RAS activation. According to the American College of Medical Genetics and Genomics criteria, the variant is likely pathogenic. Our study highlights RASAL2 c.2423 A > G as a potential biomarker for CRC risk and therapy response.

SMARCA4-deficient undifferentiated thoracic tumor (SMARCA4-UT) is a rare and highly aggressive malignancy characterized by early distant metastasis and a poor prognosis, with a median overall survival (OS) of only 4-7 months. Traditional therapies offer limited benefit, while emerging data suggest the efficacy of combined immunotherapy, chemotherapy, and anti-angiogenic approaches. We report a case of a 52-year-old male with a heavy smoking history who presented with loss of consciousness and limb convulsions. Imaging revealed brain metastasis and a thoracic tumor. After surgical removal of the brain lesion and a lung biopsy, the patient was diagnosed with SMARCA4-UT, showing no targetable driver mutations and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) < 1%. The patient underwent first-line treatment with tislelizumab, bevacizumab, carboplatin, and paclitaxel. Despite discontinuation of bevacizumab due to a tumor cavity, the patient achieved partial remission (PR) after six cycles. Notably, consolidative thoracic radiotherapy (TRT) was administered following systemic disease control to enhance local control. After 5 months of maintenance therapy, oligoprogression of the primary lung lesion was detected and the progression-free survival (PFS) of first-line treatment reached 14 months. The patient then performed salvage surgery for local lesion and continued with maintenance treatment. As of May 2025, the patient has survived for 31 months since the initial diagnosis.

Immunotherapy has emerged as an effective treatment for lung adenocarcinoma (LUAD) in recent years. However, the ability of cancer cells to suppress antitumor immune responses through multiple mechanisms has become one of the major challenges for therapy. PYCR1 can reinforce the proliferation of LUAD cells, but the function of PYCR1 in LUAD against the tumor immune response has not been fully elucidated.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by exceedingly high rates of metastatic progression, with the liver representing the most common site of distant spread. Here, we established a platform for multisite immune profiling of human PDAC encompassing the tumor, peripheral circulation, and premetastatic liver, to more comprehensively study how various immune subsets might contribute to patient outcomes.

Current American Society of Clinical Oncology guidelines state that patients with metastatic prostate cancer (MPC) should undergo germline and somatic DNA sequencing. The authors examined the utility of next-generation sequencing (NGS) on fine-needle aspiration (FNA) biopsies in which NGS was performed on cell block (CB) and/or smears.

Systemic treatment options for vulvar squamous cell carcinoma (VSCC) are limited. ROS1, a tyrosine kinase implicated, for example, in non-small cell lung cancer (NSCLC), has recently shown responsiveness to tyrosine kinase inhibitors. This study investigated immunohistochemical ROS1 expression in VSCC to explore its potential as a future therapeutic target in this rare malignancy.

To explore the clinicopathological features and the prognostic values of the co-stimulatory molecules OX40 and the inducible T-cell co-stimulator (ICOS) in Extranodal Natural Killer/T-cell Lymphoma (ENKTL).

Diffuse large B-cell lymphoma (DLBCL) is the most common hematological malignancy. More than half of DLBCL patients achieve long-term remission after treatment, but a third relapse after conventional Rituximab (R)-based chemotherapy regimens, such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). Cancer cells are exposed to chronic replication stress, which impedes the duplication of their genome. Functional DNA repair pathways are therefore important for the survival of cancer cells. This dependence can be exploited therapeutically to hamper repair of the intrinsic DNA damage occurring during replication or to exacerbate DNA damage induced by chemotherapy. Using CRISPR-Cas9 screening, we identified CHEK1, WEE1, ATR and RAD51 DNA repair factors as essential genes in DLBCL cells. According to these results, we investigated the effect of small molecules targeting DNA replication stress and DNA repair mechanisms, alone or in combination with the R-CHOP genotoxic agents, cyclophosphamide and doxorubicin. Applying a standard threshold of 2 SDs below the IC50 of the genotoxic agent alone, a total of 3 synthetic lethal combinations have been identified including cyclophosphamide with CHK1/2 inhibitor, cyclophosphamide and ATR inhibitor and doxorubicin with DNAPK inhibitor. Co-treatment with these molecules led to cell death, DNA damage induction and cell cycle arrest in DLBCL cells more efficiently than genotoxic agents alone. These data have been validated using primary DLBCL cells from patients. Our results open new perspectives for therapeutic approaches exploiting the synthetic lethality of genotoxic agents with DNA repair inhibitors to improve the therapeutic outcome of patients with DLBCL.

The progression and prognosis of early-stage lung adenocarcinoma are closely associated with histologic subtypes, yet the presence of mixed histologic patterns often complicates prognostic assessment. Currently, the correlation between molecular and histologic features remains poorly understood.

Lung cancer, a leading cause of cancer death, displays profound histologic and molecular heterogeneity across adenocarcinoma, squamous, and small-cell types. Clinically, tumours can shift between these states, reflecting lineage plasticity-the reprogramming of differentiated cells to alternate identities. Pre-existing genomic/epigenomic diversity and microenvironmental cues supply the substrates and pressures for plasticity from disease onset. This review anchors plasticity within normal lung development to clarify how fate programs are co-opted to drive progression, immune escape, therapy resistance, and invasion.

A Sister Mary Joseph's nodule is an umbilical metastasis from an intra-abdominal or pelvic malignancy, associated with a poor prognosis. Three possible metastatic pathways for Sister Mary Joseph's nodule have been postulated: hematogenous spread, lymphatic dissemination, and direct invasion. However, detailed analyses of these metastatic pathways, particularly those involving gene expression profiling, are lacking in literature. We investigated the metastatic patterns of Sister Mary Joseph's nodule by performing RNA microarray analysis of the primary tumor and each metastatic site in a case of fallopian tube cancer presenting with Sister Mary Joseph's nodule and inguinal lymph node metastases.

This retrospective cohort study explores the association between the interval of nanocarbon application before surgery and the detection of postoperative lymph nodes in patients undergoing gastric cancer surgery.

Despite the high burden and regional variability of ovarian cancer (OC), data on its status in Syria, a country impacted by long-standing conflict, remain scarce. This study aimed to provide the first nationwide analysis of OC epidemiological and clinicopathological characteristics.

Gastric cancer (GC) ranks as the fifth most prevalent malignancy and the third leading cause of cancer-related mortality worldwide, with complex pathogenesis driven by genetic and epigenetic alterations. While genetic contributors to GC have been extensively studied, the functional role of N6-methyladenosine (m6A) RNA methylation-the most abundant eukaryotic RNA modification-in gastric carcinogenesis remains insufficiently characterized. This study aimed to investigate transcriptome-wide m6A methylation dysregulation and its mechanistic implications in GC progression.

Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy with poor survival and no available effective therapy. This unmet clinical need led us to investigate chimeric antigen receptor (CAR) T cells s as potential treatment option for this malignant disease. As target tumor antigens of our CAR T cell therapy, we selected the chondroitin sulfate proteoglycan 4 (CSPG4) and the B7-homolog 3 (B7-H3), as they are both highly and homogeneously expressed on different types of thyroid carcinoma cell lines and tissues, including ATC. Importantly, both CSPG4 and B7-H3 have a low distribution on normal tissues, thus limiting 'on-target off-tumor' CAR T-related toxicities.

Oxaliplatin (OXA) is a commonly used drug for the treatment of rectal cancer (RC). However, traditional administration methods are plagued by low efficiency, high systemic side effects, and poor patient tolerance. Therefore, there is an urgent need to develop a targeted drug delivery system to enhance efficacy and reduce toxicity.