Abstract Background: Accurate early cancer detection remains a critical clinical challenge due to the high cost and limited sensitivity and specificity of conventional diagnostic methods. Indeed, non-invasive approaches capable of molecular-level characterization of biofluids are urgently needed to improve early diagnostic accuracy and patient outcomes. Artificial intelligence-assisted surface-enhanced Raman scattering (AI-SERS) offers a powerful platform to test complex metabolic signatures in urine with exceptional sensitivity. By integrating high-resolution SERS spectra with deep learning-based classification, AI-SERS platform transcends the limitations of conventional assays, enabling highly precise cancer differentiation and unlocking new avenues for the discovery of metabolite-based biomarkers for early cancer detection. Methods: This study enrolled a total of 287 clinical urine samples across six groups: prostate cancer (PRC, n = 49), pancreatic cancer (PAC, n = 16), ovarian cancer (OC, n = 64), lung cancer (LC, n = 30), breast cancer (BC, n = 29), and normal controls (NOR, n = 99). A minimal volume (10 μL) of clinical urine samples was applied to a patented SERS sensor to enhance metabolite signals, measured using a Raman spectrometer. The resulting SERS spectra were analyzed using a convolutional neural network (CNN)-based deep learning approach. Results: The SERS spectra of urine samples from 6 different groups exhibited sharp Raman spectral peaks, providing significant information for analysis. Using the developed CNN model, all cancer types combined could be distinguished from normal controls with an accuracy of 96.6%, sensitivity of 99.3%, and specificity of 94.0%, demonstrating excellent overall classification performance between cancer and non-cancer samples. Further analysis of individual cancer types versus normal controls showed robust predictive performance, with accuracy, sensitivity, and specificity of 98.0%, 98.6%, and 97.3% for PRC; 97.9%, 97.9%, and 97.9% for OC; 97.8%, 97.8%, and 97.8% for LC; and 98.9%, 97.7%, and 100% for BC, respectively. These results demonstrate the strong predictive capability of the AI-SERS platform for noninvasive, cancer-specific detection. Conclusions: The noninvasive, label-free urine analysis using the AI-SERS platform revealed remarkable test performance in classifying cancers from normal controls, offering a rapid cancer screening approach and highlighting its potential for early cancer diagnosis. Ongoing clinical studies aim to identify cancer-type-specific metabolic biomarkers to further improve diagnostic specificity and contribute to enhanced patient outcomes. Citation Format: Jeehee Kim, Hyungseok Choi, Eun Hye Koh, Thi Nhat Linh Vo, Geo Ryu, Eun Been Lee, Daekeon Kwon, Soohyun Lew, Si Young Song. Innovative label-free and non-invasive urinary metabolite analysis integrating AI and SERS technology for early cancer detection: A retrospective clinical study involving five cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2532.

Background: FOLFIRINOX and gemcitabine/nab-paclitaxel are widely used first-line regimens in metastatic pancreatic cancer (mPC); however, direct real-world comparisons and clear criteria for selecting between the two remain limited. Methods: In this retrospective cohort study, we used a multicenter real-world data registry to compare outcomes between patients with mPC treated with FOLFIRINOX and gemcitabine/nab-paclitaxel and identify genomic alterations associated with treatment response. The cohort included patients with mPC treated with FOLFIRINOX (n=272) or gemcitabine/nab-paclitaxel (n=280) between 2010 and 2022 at tertiary referral cancer centres. The primary outcomes were overall and progression-free survival. Predictive genetic markers were identified using available next-generation sequencing results. Findings: The FOLFIRINOX group was significantly younger than the gemcitabine/nab-paclitaxel group. Before propensity score matching, the FOLFIRINOX group showed significantly longer median overall and progression-free survival. Afterward, survival outcomes no longer significantly differed. Next-generation sequencing panel data were available for 57 and 29 patients in the FOLFIRINOX and gemcitabine/nab-paclitaxel groups, respectively. In the gemcitabine/nab-paclitaxel group, ARID1A and RNF43 mutations were correlated with poor progression-free survival. Genomic alterations in the TGF-β pathway were associated with improved overall survival with gemcitabine/nab-paclitaxel. Interpretation: FOLFIRINOX and gemcitabine/nab-paclitaxel demonstrated comparable survival outcomes following propensity score matching. Specific genomic alterations associated with treatment response were identified, underscoring the potential of personalized next-generation sequencing-guided treatment strategies.

Background: [68Ga]-DOTATOC PET/CT is a valuable technique for identifying neuroendocrine tumors overexpressing somatostatin receptors; however, its diagnostic and prognostic utility for WHO low-grade pancreatic neuroendocrine tumors remains unclear. Therefore, we aimed to evaluate [68Ga]-DOTATOC uptake in well-differentiated pancreatic neuroendocrine tumors and determine its predictive capability for metastasis. Methods: Patients with pathologically diagnosed well-differentiated, non-functional pancreatic neuroendocrine tumors who underwent [68Ga]-DOTATOC PET/CT between 2015 and 2021 were included. Medical records and [68Ga]-DOTATOC PET/CT indices (maximal and mean standardized uptake values, somatostatin receptor-expressing tumor volume, and total lesion somatostatin receptor expression in pancreatic tumors) were retrospectively reviewed. Correlations between indices were analyzed to determine their collective diagnostic significance. Results: Among 93 patients who were pathologically diagnosed with pancreatic neuroendocrine tumors and underwent [68Ga]-DOTATOC PET/CT, 48 with well-differentiated, non-functional pancreatic neuroendocrine tumors without accompanying genetic syndromes were included. The pancreatic neuroendocrine tumors were classified as WHO grade 1 (n = 30, 62.5%) and grade 2 (n = 18, 37.5%), with tumors in 25% of the patients exhibiting initial metastases. A higher incidence of metastasis was observed in larger metabolically active tumors (somatostatin receptor-expressing tumor volume, p < 0.001; total lesion somatostatin receptor expression, p < 0.001). Conclusions: Volumetric parameters derived from [68Ga]-DOTATOC PET/CT correlates with initial metastasis in well-differentiated pancreatic neuroendocrine tumors.

Cancer metastasis is the leading cause of cancer-related deaths, making early detection and the prevention of metastatic progression critical research priorities. Recent studies have expanded our understanding of CEMIP (KIAA1199, HYBID), revealing its involvement in cancer metastasis and its potential role in slowing cancer progression. CEMIP plays critical roles in several stages of cancer metastasis: First, CEMIP promotes cancer cell proliferation to maintain cell heterogeneity before the metastasis process. Second, it facilitates cancer cell detachment by promoting the epithelial-mesenchymal transition (EMT) through alterations in signaling pathways. Third, CEMIP contributes to cancer cell adherence and attachment by enabling cells to withstand cell death (anoikis and ferroptosis) and hypoxia. Fourth, during the invasion process, CEMIP induces hyaluronan depolymerization and further modulates signaling to promote EMT. Lastly, in the pre-metastatic niche, CEMIP influences the tumor microenvironment through hypoxia, angiogenesis, signaling pathway changes, and hyaluronan degradation. Recent studies have focused on leveraging CEMIP as a diagnostic tool or a predictor of metastasis and/or targeting CEMIP to overcome cancer resistance and progression. This review aims to explore the role of CEMIP at each stage of cancer metastasis and highlight recent advances in targeting CEMIP to inhibit cancer progression.

Discovery and verification of diagnostic or therapeutic biomarkers for biliary tract cancer (BTC) is challenging owing to the low prevalence of the disease. Here, we identified and investigated the clinical impact of a fusion gene, Pumilio1-tumor necrosis factor receptor-associated factor 3 (PUM1-TRAF3), caused by 1;14 chromosomal translocation in BTC. PUM1-TRAF3 was initially identified in the RNA-sequencing of five BTC surgical tissues and confirmed by fluorescence in situ hybridization. Expression of the fusion gene was validated in an expanded cohort (5/55, 9.1%). Establishment and molecular assessment of PUM1-TRAF3 expressing BTC cells revealed that PUM1-TRAF3 activates non-canonical NF-κB signaling via NF-κB-inducing kinase (NIK). Abnormal TRAF3 activity, driven by competitive binding of PUM1-TRAF3 and TRAF3 to NIK, led to NIK rescue followed by P52/RelB nuclear translocation, all of which were reverted by an NIK inhibitor. The elevated expression of NIK and activated NF-κB signaling was observed in the PUM1-TRAF3-expressing regions of patient tissues. Expression of the PUM1-TRAF3 fusion was significantly correlated with strong NIK expression, which is associated with a poorer prognosis for patients with BTC. Overall, our study identifies a new fusion gene, PUM1-TRAF3, that activates NIK and non-canonical NF-κB signaling, which may be beneficial for developing precise treatment strategies for BTC.

Background Biliary tract cancer (BTC) is a relatively rare but aggressive gastrointestinal cancer with a high mortality rate. Cancer stem cell (CSC) populations play crucial roles in tumor biology and are responsible for the low response to anti-cancer treatment and the high recurrence rate. This study investigated the role of Transgelin-2 ( TAGLN2 ), overexpressed in CSC in BTC cells, and analyzed its expression in patient tissues and serum to identify potential new targets for BTC. Methods TAGLN2 expression was suppressed by small-interfering or short hairpin RNAs, and its effects on tumor biology were assessed in several BTC cell lines. Furthermore, the effects of TAGLN2 silencing on gemcitabine-resistant BTC cells, differentially expressed genes, proteins, and sensitivity to therapeutics or radiation were assessed. TAGLN2 expression was also assessed using western blotting and immunohistochemistry in samples obtained from patients with BTC to validate its clinical application. Results Suppression of TAGLN2 in BTC cell lines decreased cell proliferation, migration, invasion, and tumor size, in addition to a reduction in CSC features, including clonogenicity, radioresistance, and chemoresistance. TAGLN2 was highly expressed in BTC tissues, especially in cancer-associated fibroblasts in the stroma. Patients with a low stromal immunohistochemical index had prolonged disease-free survival compared to those with a high stromal immunohistochemical index (11.5 vs. 7.4 months, P = 0.013). TAGLN2 expression was higher in the plasma of patients with BTC than that in those with benign diseases. TAGLN2 had a higher area under the curve (0.901) than CA19-9, a validated tumor biomarker (0.799; P < 0.001). Conclusion TAGLN2 plays a critical role in promoting BTC cell growth and motility and is involved in regulating BTC stemness. Silencing TAGLN2 expression enhanced cell sensitivity to radiation and chemotherapeutic drugs. The expression of TAGLN2 in patient tissue and plasma suggests its potential to serve as a secretory biomarker for BTC. Overall, targeting TAGLN2 could be an appropriate therapeutic strategy against advanced cancer following chemotherapy failure.

Biliary tract cancers (BTCs), including intrahepatic, perihilar, and distal cholangiocarcinomas, as well as gallbladder cancer, are a diverse group of cancers that exhibit unique molecular characteristics in each of their anatomic and pathological subtypes. The pathological classification of BTCs compromises distinct growth patterns, including mass forming, periductal infiltrating, and intraductal growing types, which can be identified through gross examination. The small-duct and large-duct types of intrahepatic cholangiocarcinoma have been recently introduced into the WHO classification. The presentation of typical clinical symptoms, as well as the extensive utilization of radiological, endoscopic, and molecular diagnostic methods, is thoroughly detailed in the description. To overcome the limitations of traditional tissue acquisition methods, new diagnostic modalities are being explored. The treatment landscape is also rapidly evolving owing to the emergence of distinct subgroups with unique molecular alterations and corresponding targeted therapies. Furthermore, we emphasize the crucial aspects of diagnosing BTC in practical clinical settings.

BACKGROUND:Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity. METHODS:We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples. RESULTS:We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep_VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep_VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data. CONCLUSIONS:This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets.

Background: The TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC.. MethodsPatients recruited from 16 hospitals received gemcitabine (1000 mg/m(2), D 1, 8, and 15)/capecitabine (830 mg/m(2) BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2-4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety. Results: Total 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively. Conclusions: GV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC.Clinical trial registrationNCT02854072.

Purpose: Hypoxaemia is a significant adverse event during endoscopic retrograde cholangiopancreatography (ERCP) under monitored anaesthesia care (MAC); however, no model has been developed to predict hypoxaemia. We aimed to develop and compare logistic regression (LR) and machine learning (ML) models to predict hypoxaemia during ERCP under MAC. Materials and Methods: We collected patient data from our institutional ERCP database. The study population was randomly divided into training and test sets (7:3). Models were fit to training data and evaluated on unseen test data. The training set was further split into k-fold (k=5) for tuning hyperparameters, such as feature selection and early stopping. Models were trained over k loops; the i-th fold was set aside as a validation set in the i-th loop. Model performance was measured using area under the curve (AUC). Results: We identified 6114 cases of ERCP under MAC, with a total hypoxaemia rate of 5.9%. The LR model was established by combining eight variables and had a test AUC of 0.693. The ML and LR models were evaluated on 30 independent data splits. The average test AUC for LR was 0.7230, which improved to 0.7336 by adding eight more variables with an l(1) regularisation-based selection technique and ensembling the LRs and gradient boosting algorithm (GBM). The high-risk group was discriminated using the GBM ensemble model, with a sensitivity and specificity of 63.6% and 72.2%, respectively. Conclusion: We established GBM ensemble model and LR model for risk prediction, which demonstrated good potential for preventing hypoxaemia during ERCP under MAC.

According to the 2019 WHO classification, epithelial gallbladder (GB) tumors are categorized into “benign epithelial tumors and precursors” or “malignant epithelial tumors” (Table 1) [1]. Several terms have been used to describe the overlapping morphological entities of premalignant GB lesions over the years. This has led to varying incidence and outcomes for premalignant GB lesions [2]. Thus, a large part of the pathological and clinical characteristics of these lesions are still not clear. In the 2010 WHO classification, the former terms of premalignant GB lesions were recategorized according to their morphological and pathophysiologic characteristics. For the flat microscopic lesion, the previously used term “flat dysplasia” was replaced by “biliary intraepithelial neoplasm (BilIN).” Furthermore, the terms for premalignant exophytic GB neoplasms greater than 1 cm were unified as intracholecystic papillary neoplasms (ICPN). Both BilIN and ICPN have counterparts in other pancreaticobiliary systems (Table 2). A notable change in the WHO classification for 2019 is that the classification system of premalignant lesion changed from a three-tier to a two-tier classification system, with the former low- and intermediate-grade intraepithelial neoplasia or BilIN-1 and BilIN-2, now classified as low-grade, consistent with tumors from other digestive system. Conventional diagnostic imaging modalities for GB cancer showed reliable diagnostic performance, and several new techniques have recently emerged for preoperative imaging and histological diagnosis of GB cancer. In this chapter, the pathology and pathogenesis, as well as the clinical features and diagnosis of GB cancer, will be reviewed.

Hospice care, a subtype of palliative care, focuses on end-of-life care for patients with a life expectancy of only a few months. Hospice care aims to control the painful symptoms of terminally ill patients and even help patients and their families with mental, social, and spiritual problems. In recent years, the importance of active application of advance care planning (ACP) and end-of-life care is emerging with increasing interest in life extension and dignity of death. Consequently, an accurate understanding of hospice care and a change in perception are necessary.

Radiotherapy is a local treatment and is commonly used as an adjuvant treatment before or after surgery for rectal cancer with a high probability of recurrence, that is, stage II or III. In the case of distant metastasis that can be resected even in stage IV, adjuvant radiation therapy can be performed and can be used to prevent recurrence after local excision of stage I cancer or as a first-line treatment when surgery is impossible or difficult. In addition, if surgery to preserve anal function is difficult due to the location or size of the tumor, radiation therapy before surgery can reduce the extent of the tumor and preserve the anus.

Cholangiocarcinoma (CCA) staging is most commonly classified using the TNM staging systems of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC), which came into effect on January 1, 2018, in its eighth edition. There are separate systems depending on whether the CCA arises primarily from intrahepatic (iCCA), perihilar/hilar (Klatskin) (pCCA), or extrahepatic (distal) bile ducts (dCCA), which all differ in their definitions of tumor stage (T) and in their prognostic stage groupings (Fig. 1a).

Gastric cancer is the third leading cause of cancer mortality after lung and colorectal cancer and the fifth in incidence. Once gastric cancer is histologically diagnosed, the next important step is staging, which can determine the direction of the treatment approach (curative or palliative). In addition, survival and prognosis vary significantly depending on the stage of the disease at the time of diagnosis. Since the eighth Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging manual including the clinical stage and post-neoadjuvant stage has been released, clinicians have received improved guidance on treatment-decision making and prognostic information throughout the treatment course. Here, we will review the diagnosis, staging, and prognosis prediction in patients with gastric cancer.

About 40% of esophageal cancers have metastasized to distant lymph nodes or other organs at the time of diagnosis [1]. Recurrence is also experienced in 21–39% of patients who achieve complete pathological remission through multidisciplinary treatment of advanced esophageal cancer. Although recurrent/metastatic esophageal cancer has an extremely poor prognosis (<5% in 5-year survival rate) [1], a meta-analysis of the Cochrane review published in 2017 confirmed that palliative chemotherapy was more effective than best supportive care in improving overall survival (OS) and quality of life and for alleviating symptoms such as dysphagia [2]. In recent years, more treatment options have emerged as a result of research on new targeted drugs and immunotherapy [3, 4]. In this chapter, palliative combination chemotherapy, which is widely used for metastatic or recurrent advanced esophageal cancer, is discussed, and the therapeutic effects of recently implemented targeted chemotherapy and immunotherapy are summarized (Tables 1 and 2).

The diagnosis and treatment of cancer can affect patients and their families both emotionally and physically. Distress in cancer patients is a multifactorial, unpleasant emotional experience of a psychological, social, and/or spiritual nature that can interfere with the ability to cope effectively with cancer, its physical symptoms, and its treatment [1]. Distress has recently been considered the sixth vital sign in cancer care along with temperature, respiration, heart rate, blood pressure, and pain and should be recognized, monitored, documented, and treated promptly at all stages of the disease and in all settings [2].

The term “anal cancer” usually refers to a squamous cell cancer (SCC) of the anal canal, which represents the majority of cancers arising in the anal region. This chapter will cover adjuvant and palliative chemotherapy of anal SCC.

The term pancreatic neuroendocrine neoplasm (PNEN) encompasses a diverse set of tumors arising in the pancreas neuroendocrine progenitor cell. PNEN is a rare disease but exhibits a wide spectrum of clinical behavior. Well-differentiated PNENs are referred to as pancreatic neuroendocrine tumors (PNET), while poorly differentiated high-grade PNENs are referred to as pancreatic neuroendocrine carcinomas (PNEC) but exhibit a wide spectrum of clinical behavior that has made classification and treatment difficult. While most PNENs are associated with relatively good survival, there can be significant variability in outcomes based on their biological heterogeneity. In this chapter, the diagnosis and treatment of PNENs will be introduced and described in detail.

Colorectal cancer (CRC) is the third most common cancer worldwide. The incidence of CRC tends to increase with societal and economic development and to stabilize or decrease in highly developed countries with higher rates compared to other countries [1]. This phenomenon is probably attributable to the changing risk factors (e.g., dietary patterns, physical inactivity, visceral fat, alcohol intake, and smoking) and increased CRC screening programs [2]. Furthermore, the progression of carcinogenesis is divided into the stage of initiation, promotion, and progression [3]. In most cases of colorectal carcinogenesis, genetic and epigenetic alterations are involved in each step originating from a benign precursor lesion, defined as a polyp [4]. A classic pathway, the sequence of adenoma-carcinoma (85–90% of sporadic CRC) [5, 6], the serrated pathway (10–15% of sporadic CRC) [7, 8], and the inflammatory pathway (<2% of all CRC) [9, 10] are three distinct pathways of colorectal carcinogenesis. Therefore, primary prevention of CRC should focus on modification of the modifiable lifestyle and nutritional risk factors (approximately 47% of CRC in the United States of America and 45% in the United Kingdom are likely attributable to modifiable risk factors [11]) and chemoprevention of known mechanisms of colorectal carcinogenesis. Furthermore, the optimal timing and method of CRC screening could contribute to the secondary prevention of CRC.