Several clinico-pathological prognostic factors are essential to guide therapeutic management for colon cancer (CC). The benefit of adjuvant chemotherapy remains controversial for patients with stage II CC and is currently not systematically applied. This leads to define two subgroups of patients, "low" and "high risk" of recurrence. In this setting, tumor-infiltrating lymphocytes (TILs) may represent a promising marker.

The emergence of immune checkpoint inhibitors (ICIs) has transformed the treatment landscape of metastatic melanoma. However, despite its success, reliable biomarkers for predicting primary resistance are not available in clinical practice. This study seeks to identify predictors of primary resistance based on novel gene expression signatures. The transcriptomic profile of the tumor microenvironment was analyzed using tissue samples from 46 metastatic cutaneous melanoma patients collected prior to the initiation of ICIs therapy. A primary resistance predictive model was trained with the Discovery FFPE RNA-seq subcohort and validated using an independent external cohort of 54 samples. Additionally, liquid biopsy samples from peripheral blood mononuclear cells were analyzed in 8 patients using single-cell RNA sequencing (scRNA-seq) and in 46 patients using flow cytometry. We identified an 82-gene transcriptomic signature composed of tumor- and immune-related genes that stratifies metastatic cutaneous melanoma patients based on primary resistance to ICIs, with key markers including CXCL13, WDR63, MZB1, FDCSP, IGKC and GRIK3. This signature achieved an AUC of 0.814. Immune deconvolution guided by scRNA-seq revealed four immune cell subsets (Plasma cells, Pre-B cells, memory CD4⁺ T cells, and naive CD4⁺ T cells) as prognostic indicators of resistance. We propose a transcriptomic biomarker signature that accurately predicts primary resistance to ICIs in metastatic cutaneous melanoma. Through the integration of immune deconvolution with circulating immune cell profiles, we derived an ImmuneSignature linked to patient survival. By combining these approaches, we provide a framework for enhancing the prediction of immunotherapy outcomes and offer a novel strategy for identifying therapeutic targets to overcome resistance.

Women diagnosed with ductal carcinoma in situ (DCIS) and clinicians have reported challenges in communication about DCIS, contributing to women's confusion and anxiety. This study explored how to improve communication about DCIS including alternative labels, language and other strategies.

Studies have shown that malignant pulmonary nodules frequently occur in the upper lobes of the lung. However, there is no data on their distribution according to segments. The aim of this study is to predict the histological subtype of lung cancer based on the segment localization of malignant pulmonary nodules located in the upper lobe of the lung.

Metastatic tumors-secondary malignancies arising from the hematogenous or lymphatic dissemination of cancer cells from primary lesions to distant sites-account for nearly 90% of cancer-associated mortality worldwide. Consequently, studying the effect of epithelial-mesenchymal transition (EMT) on metastatic tumors using experimental data and partial differential equation (PDE) modeling is essential. This study innovatively established a phenotype- and density-regulated chemotaxis coefficient to develop a PDE model characterizing cancer cell migration, proliferation, and EMT, enabling analysis of EMT behavior within the tumor microenvironment and its impact on spreading patterns. Subsequently, incorporating the mechanisms of anti-TGF β RII and cyclophosphamide (CTX), three therapeutic models for tumor metastasis were constructed, with parameter estimation based on experimental data. To predict primary tumor distant metastasis risk, we originally established a tumor metastasis incidence index, thereby evaluating the critical roles of EMT-targeting and cytotoxic chemotherapeutic drugs in tumor progression. Our findings demonstrate that appropriate pharmacological intervention effectively suppresses tumor dissemination, with therapeutic efficacy significantly enhanced upon EMT inhibition. This study establishes a theoretical framework for designing cancer treatment strategies and provides foundational insights for developing personalized therapeutic regimens.

Uterine leiomyosarcoma (uLMS) is a rare but aggressive malignant mesenchymal tumor, accounting for 2-5% of uterine malignancies. Because its symptoms and imaging features often resemble those of benign uterine leiomyoma (LM), accurate preoperative diagnosis remain difficult. This review summarizes recent advances in liquid biopsy for uLMS and explores its potential for early detection, molecular characterization, and treatment monitoring.

Cancer-derived extracellular vesicles (EVs), particularly exosomes, transfer oncogenic proteins, metabolites and nucleic acids to both nearby and distant cells. These diverse bioactive molecules act synergistically to promote cancer progression by simultaneously modulating multiple signaling networks in recipient cells. By inducing coordinated and complex molecular reprogramming, exosomes provide tumors with a powerful mechanism to drive the diverse processes required for malignant growth, invasion, metastasis and immune modulation. This review integrates recent and landmark studies from primary studies of tumor exosomes and how they influence critical features of cancer as defined in the updated 2022 Hallmarks of Cancer framework. Tumour-derived exosomes not only drive proliferative signalling and metabolic rewiring, but also actively reprogram the stromal and immune compartments of the tumour microenvironment and condition distant tissues to form metastatic niches. In particular, we focus on hypoxia-driven exosome biology. The low-oxygen conditions that characterize most solid tumors enhances exosomal biogenesis and selectively enriches cargo with active molecules to promote angiogenesis, cancer cell survival, epithelial-mesenchymal transition, immune evasion and metastasis. The hypoxia-conditioned exosomes act as long-range carriers of stress-adaptation signals, extending the influence of the hostile tumour microenvironment to diverse cell types. Furthermore, we examine emerging roles for tumor-derived exosomes in modulating host-microbial interactions and influencing the efficacy of immune checkpoint inhibitors, highlighting vesicle-mediated communication between tumors, the immune system, and polymorphic microbiomes. We also explore the potential of targeting exosome-mediated pathways for therapeutic and diagnostic applications. By mapping recent experimental findings onto the updated hallmarks of cancer, this review integrates the central role of exosomes in malignant progression and highlights their potential as therapeutic targets in the clinic.

Opioid prescribing at the end of life varies widely across clinical contexts, yet real-world evidence from Asian advanced cancer populations remains limited. This study characterized end-of-life opioid prescribing patterns and examined differences according to palliative care consultation status.

Macrophages, the predominant immune-related stromal cells within tumor microenvironment, could be polarized into M1 and alternative M2 macrophages. M1 macrophages are pro-inflammatory and eliminate cancer cells, whereas M2 macrophages are immunosuppressive and facilitate tumor growth. Mounting evidence has shown that M2 macrophages are responsible for a poor prognosis in triple negative breast cancer (TNBC) patients. Since neoadjuvant chemotherapy is becoming the foundation treatment for TNBC, the relationship between M2 macrophages and response to neoadjuvant chemotherapy remains to be elucidated. Infiltration of M2 macrophages were checked by analyzing the CD163 levels on surgical resection specimens from 42 Chinese TNBC patients treated with neoadjuvant chemotherapy. Evaluation of M2 macrophages together with other immune markers including CD8-positive cytotoxic T cells and PD-L1 expression in TNBC and its association with pCR after neoadjuvant chemotherapy were performed. Pathological complete response (pCR) was significantly associated with younger age, higher tumor or stromal PD-L1 expression, higher levels of tumor or stromal CD8-positive cytotoxic T cells, but lower infiltration of CD163-positive M2 macrophages, with the level of CD163-positive M2 macrophages in stromal area as the strongest factor. Our study showed that high infiltration of CD163-positive M2 macrophages was negatively associated with the chemotherapeutic response to neoadjuvant chemotherapy in Chinese TNBC patients and could be used as a promising prognostic candidate for Chinese TNBC patients treated with neoadjuvant chemotherapy.

Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) represents a major clinical challenge due to its limited response to conventional treatment and poor prognosis. Peptide receptor radionuclide therapy (PRRT) has emerged as a promising treatment modality in patients with somatostatin receptor (SSTR)-positive tumors. We present an 82-year-old female patient with RAIR-DTC who underwent six cycles of PRRT after demonstrating SSTR positivity on Ga-68 DOTATATE positron emission tomography/computed tomography. This case highlights the limited therapeutic efficacy of PRRT in RAIR-DTC, despite favorable imaging characteristics. It underscores the need for better patient selection and further research to clarify the role of PRRT in this population.

Thyroid papillary carcinoma (PTC) is the most common carcinoma of thyroid carcinomas and endocrine carcinomas. The diagnosis of thyroid PTC is made mainly by the presence of nuclear features such as nuclear clearing, groove, and nuclear inclusions. Some benign lesions of the thyroid may have nuclear features and growth patterns of papillary thyroid carcinomas, which can make the differential diagnosis difficult. Different immunohistochemical markers have always been needed to reduce diagnostic errors and detect malignancies in routine practice. As in all tumor cases, studies continue to understand carcinogenesis in thyroid carcinomas. One of the ways that can help understand this involves the use of new and effective immunohistochemical markers.

The treatment of endometrial cancer (EC) includes surgical procedures which clinicians follow with radiotherapy (RT) for patients who have specific risk factors, but there is insufficient research about how RT affects pelvic blood vessels and rectal tissues during the first period after treatment. The research used contrast-enhanced magnetic resonance imaging (CE-MRI) to study changes in pelvic blood vessel dimensions and rectal tissue parameters that occur during the initial stages of external beam radiotherapy (EBRT) treatment for EC. Methods: Ninety-five female patients who underwent postoperative adjuvant EBRT for EC were included in the study. CE-MRI examinations were performed before radiotherapy (RT0) and at the 3-month post-radiotherapy follow-up (RT1). Rectum internal diameter (RID), rectum external diameter (RED), right external iliac artery diameter (REIAD), left external iliac artery diameter (LEIAD), right femoral artery diameter (RFAD), and left femoral artery diameters (LFAD) were measured in centimeters. Paired comparisons between RT0 and RT1 measurements were performed.

Chemotherapy Response Score (CRS) is a three-tier histopathologic system evaluating response to neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC).

Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor. Although it accounts for only about 13% of all lung cancers, its rapid proliferation, early metastasis, and very poor prognosis result in an extremely low five-year survival rate. In recent years, immune checkpoint inhibitors have improved outcomes in a subset of patients; however, the proportion of patients who derive meaningful benefit remains limited. For patients with limited-stage SCLC (LS-SCLC) undergoing chemoradiotherapy (CRT), standardized serum biomarkers suitable for routine monitoring of treatment response and early detection of relapse have yet to be established. Progastrin-releasing peptide (ProGRP) is generally more specific than neuron-specific enolase (NSE) for SCLC, yet neither marker is diagnostic when used alone. This review summarizes the roles of ProGRP and NSE in LS-SCLC during chemoradiotherapy (CRT), with an emphasis on differential diagnosis (particularly when pleural effusion cytology suggests adenocarcinoma but ProGRP is markedly elevated-raising the possibility of SCLC, mixed histology, or transformation and underscoring the need for tissue confirmation), longitudinal monitoring, and prognostic implications. Notably, universally accepted cut-off values for survival prediction are lacking; therefore, clinical interpretation should focus on within-assay dynamic trends and incorporate potential interfering factors, including renal dysfunction and hemolysis.

Drug-induced lung disease (DILD) is a severe adverse event of cancer treatment. Several clinical reports have demonstrated an association between DILD and tumor progression. However, the underlying mechanism remains unclear. This study aimed to elucidate the role of tumor-bearing status in the development of DILD.

MR-guided laser interstitial thermal therapy (LITT) offers a minimally invasive option for recurrent glioblastoma, but human post-treatment tissue data are scarce. In this case report, post-LITT tissue exhibited distinct zonal changes, including central necrosis within the ablation zone and reduced tumour proliferation with increased CD8+ T-cell infiltration in the perilesional transition zone, suggesting that LITT may influence the local immune landscape in recurrent glioblastoma.

The addition of immune checkpoint inhibitor (ICI) to platinum-based chemotherapy has improved outcomes in patients with advanced non-small cell lung cancer (NSCLC). However, evidence on the efficacy of adding ICI to platinum retreatment in patients who relapse after perioperative platinum-based chemotherapy remains limited.

Three-dimensional (3D) models more closely represent the in vivo situation and are therefore more relevant models for drug screening. Among the more than twelve regulated cell death (RCD) modalities, immunogenic cell death (ICD) stands out for its ability to initiate efficient anti-tumor immune response. For example, ferroptosis, which can be induced via the inhibition of GPX4 leading to uncontrolled lipid peroxidation, might be immunogenic under certain conditions. It is crucial to identify which cell death modality is induced, as certain cancer types exhibit resistance to specific forms of cell death. However, a major limitation of 3D models is the lack of high-throughput assays, which often require dissociation of the 3D models, potentially leading to misinterpretation of results. Here, we describe a protocol for identifying and quantifying the induction of RCD modalities in 3D models, such as spheroids. This method eliminates the need for tumor spheroid dissociation and is compatible with other screening techniques, including confocal microscopy. This protocol enables high-throughput screening of various cell death inducers in intact 3D models, serving as a crucial first step in the identification of novel inducers and their specificity for particular ICD and RCD types.

Nanoparticles (NPs), the most common physical form of drug or therapeutic delivery systems enhance treatment safety and efficacy thanks to protection and vehiculation of their payload into the targeted tissue. Recently, nanomedicines have received increasing interest in the area of cancer therapeutics. However, the failure to overcome biological barriers at the tissue and cellular levels prevents NP distribution and delivery, which carries unsuccess in clinical trials. With the introduction of advanced three-dimensional (3D) tumor replicas such as cancer spheroids and patient-derived organoids (PDOs) that provide a physiological 3D tissue-like context, the intrinsic NP-cell interaction features such as cellular uptake and intratumor behavior can be directly tested on a translational and preclinical basis. High-content screening (HCS) plays a pivotal role for predicting the efficacy of each NP design in an automated and unbiassed manner. This chapter presents in detail some protocols developed for confocal microscopy HCS on miniaturized cultures of tumor spheroids and PDOs, quantitative profiling of NP intra-spheroid transport and RNA-interference screening to unveil NP penetrance cellular effectors. In perspective, these modules put together, envision a core for a nano-PDO HCS workflow to advance cancer nanomedicine development.

Here we detail a method for the exploration of patient-derived xenografts (PDX) based on organoids (PDX-O), using antibodies validated for immunohistochemistry. Importantly this approach can be used to characterize the response of malignant cells to antineoplastic treatments. Cancer progression and metastasis reflect tumor heterogeneity and plasticity. Here we analyzed cells in PDX grown as spheroids or tumoroids embedded in collagen/basement membrane extract (BME) matrix. The use of 3D cellular models instead of 2D allows the inclusion in the study of non-adherent tumors. Even if the cells are adherent the spheroid and tumoroids conformation or organization in space and cellular polarity differ for 2D. This difference can change the response to treatment. Adding a matrix component is an important addition to the tumoral microenvironment that can change also the cellular response to treatment. We combined this tridimensional model with a multiplexed staining protocol to analyze tumor cell differentiation and responses to drugs. We analyzed paraffin embedded organoid sections, allowing to analyze the core of cell aggregates, and analyzed cell plasticity, differentiation and proliferation with and without treatment with palbociclib. Spheroids included an outer layer of luminal cytokeratin (CK) 8-positive cells surrounding a mixed population of cells expressing both CK5 and CK8. Palbociclib treatment resulted in a proliferation arrest, linked to dedifferentiation of the cancer cells that switched to a mostly basal phenotype, supporting a hybrid CK5/CK8 phenotype. In summary, this method offers a simple and versatile strategy to analyze tumor cell responses to drugs, using routine antibodies validated for immunohistochemistry and multiplex analysis.