Onco

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by late diagnosis, early metastasis, and poor response to therapy. Liquid biopsy approaches, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes, offer a minimally invasive method to monitor tumor burden, progression, and treatment response in real time. This review aims to synthesize recent findings on CTCs in PDAC, evaluate detection technologies, and explore their clinical and translational potential. Methods: We conducted a comprehensive literature search using PubMed and Google Scholar, focusing on original studies and reviews published within the past 15 years. Articles were selected based on relevance to CTC biology, detection methods, clinical correlations, and integration with other biomarkers. Attention was paid to studies published since 2018 and landmark earlier works. Results: CTCs are detectable in PDAC patients and are consistently associated with worse survival and higher recurrence rates. However, detection sensitivity varies widely by method. EpCAM-based platforms like CellSearch^® detect CTCs in ~7–48% of cases, while newer size-based and microfluidic approaches report rates above 75%. CTCs exhibit epithelial–mesenchymal and stem-like phenotypes and can form clusters with high metastatic potential. Recent studies demonstrate molecular heterogeneity and show that CTC-derived organoids are feasible for functional studies. Nonetheless, technical variability and the lack of standardization remain major obstacles. Conclusions: CTCs represent a promising biomarker for prognosis and treatment monitoring in PDAC. Further refinement of enrichment techniques, molecular profiling strategies, and prospective clinical validation are needed to integrate CTC assays into routine PDAC management.

Objectives. Pancreatic cancer remains one of the most lethal malignancies, and the lack of effective therapies highlights the need for novel treatment strategies. In this study, we evaluated the antitumor potential of the attenuated Streptococcus pyogenes strain GURSA1—engineered to knockout the M protein completely—in a murine model of orthotopically transplanted pancreatic ductal adenocarcinoma. Methods. Female C57Bl/6 mice received intratumoral injections of GURSA1 at doses of 5 × 10⁵ or 1 × 10⁶ CFU per animal. Animal survival, body weight, tumor engraftment, metastasis intensity, tumor mass and volume, and hematological, biochemical, histological, and microbiological parameters were assessed. Results. Intratumoral administration of GURSA1 produced dose-dependent antitumor effects on tumor growth and metastatic burden, but did not result in a statistically significant survival benefit. The strain reduced tumor engraftment, the overall metastasis score, and the incidence of hemorrhagic ascites, while also decreasing tumor mass and volume, with the strongest effects observed at a dose of 1 × 10⁶ CFU. Treatment increased platelet counts and reduced urea and ALT levels toward values observed in intact mice, without affecting anemia, neutrophilia, or changes in AST, alkaline phosphatase, glucose, and total protein levels. Conclusions. These findings demonstrate that GURSA1 attenuates partial reduction in primary tumor burden in vivo and support further investigation of this strain as a potential oncolytic agent.

Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine disease marked by rapid growth, early metastatic spread, and poor outcomes. The addition of immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis to first-line chemotherapy has recently reshaped the treatment landscape for extensive-stage SCLC (ES-SCLC); however, the resulting survival gains remain modest compared with non-small lung cancer (NSCLC). This review explores the molecular features of the SCLC immune landscape that contribute to its predominantly “cold” tumor phenotype, including low MHC class I expression, T-cell exhaustion, and a profoundly immunosuppressive tumor microenvironment (TME). We summarize key clinical findings from landmark trials and examine mechanisms of both primary and acquired resistance against ICIs in SCLC. In addition, we have reviewed the growing role of precision medicine in SCLC, including molecular subtyping (SCLC-A, -N, -P, and -I) and the development of next-generation immunotherapies such as bispecific T-cell engagers (BiTEs), B7-H3, targeted therapy, and antibody–drug conjugates. By combining existing clinical evidence with new molecular insights, this review article presents strategies to overcome the existing therapeutic plateau and enhance personalized immunotherapy approaches in SCLC.