Journal of Gastrointestinal Cancer最新文献

{"title":"Preoperative Carcinoembryonic Antigen as a Predictor of 5-Year Survival in Rectal Cancer: Proposing a New Prognostic Cutoff.","authors":"Amir Keshvari, Seyed Mohsen Ahmadi Tafti, Mohammad Reza Keramati, Mohammad Sadegh Fazeli, Alireza Kazemeini, Behnam Behboudi, Reza Akbari Asbagh, Anahita Mirzasadeghi","doi":"10.1007/s12029-025-01175-2","DOIUrl":"10.1007/s12029-025-01175-2","url":null,"abstract":"<p><strong>Purpose: </strong>Carcinoembryonic antigen (CEA) is an important prognostic factor for rectal cancer. This study aims to introduce a novel cutoff point for CEA within the normal range to improve prognosis prediction and enhance patient stratification in rectal cancer patients.</p><p><strong>Methods: </strong>A total of 316 patients with stages I to III rectal cancer who underwent surgical tumor resection were enrolled. The Cox proportional hazards regression model was used to evaluate the impact of preoperative CEA level and other co-variates on overall survival (OS). The Youden Index method was used for CEA optimal cutoff estimation.</p><p><strong>Results: </strong>The mean follow-up period was 46.47 months. In risk-adjusted Cox proportional analysis, higher preoperative CEA levels (HR 1.17, CI 1.131.21; P < 0.001), and T-stage were associated with poor OS. The mean preoperative CEA level was significantly higher in patients with positive lymphovascular invasion (LVI) and perineural invasion (PNI) (CI: 1.06-2.45 and 0.75-2.33, respectively, P < 0.001, t test). Pathologic complete response (pCR) occurred in 71 (22.4%) cases. Patients with pCR had lower levels of preoperative CEA than non-pCR group (P = 0.002, CEA_pCR-CEA_nonpCR =  - 1.3; t test). Using Youden Index, the estimated optimal CEA cutoff value for predicting OS was 2.8 ng/mL (sensitivity 90%; specificity 78.5%). Lower preoperative CEA levels predict higher pCR rates, aiding patient stratification and planning.</p><p><strong>Conclusion: </strong>Preoperative CEA may play a role in the prediction of pCR in rectal cancer. Considering the CEA level of 2.8 ng/ml, as a newly defined cutoff point, patients with a worse prognosis can be identified prior to operation. PNI, along with LVI as independent predictors, may be contemplated as prognostic indicators to improve treatment strategies.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"46"},"PeriodicalIF":1.6,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving Paradigms in the Treatment of Oligometastatic Pancreatic Ductal Adenocarcinoma.","authors":"Enoch Chang, Alexander D Sherry, Jakob Liermann, Amir Abdollahi, Ching-Wei D Tzeng, Chad Tang, Todd A Aguilera, Eugene J Koay, Prajnan Das, Albert C Koong, Shubham Pant, Ethan B Ludmir","doi":"10.1007/s12029-024-01145-0","DOIUrl":"10.1007/s12029-024-01145-0","url":null,"abstract":"<p><p>Multiple randomized trials have suggested that the addition of comprehensive metastasis-directed therapy to best systemic therapy improves disease control and survival among patients with oligometastatic disease, even for histologies with a high propensity for rapid spread. Here, we review the growing literature supporting the oligometastatic paradigm in pancreatic ductal adenocarcinoma. We summarize key details from nascent institutional series and reflect on the recently reported phase II randomized EXTEND trial. We discuss various strategies for enhancing the clinical and technical implementation of metastasis-directed therapy in this patient population. Lastly, we highlight multiple ongoing landmark trials seeking to optimize and validate the role of metastasis-directed therapy in oligometastatic pancreatic cancer. Ultimately, these and other continued clinical and translational research efforts will be critical to improve care and outcomes for patients with oligometastatic pancreatic ductal adenocarcinoma.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"47"},"PeriodicalIF":1.6,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Risk Factors of Acute Kidney Injury After Colorectal Cancer Surgery.","authors":"Ahmed ElSaeed Abdulgalil, Islam H Metwally, Mohammad Zuhdy, Reham Alghandour, Shehab Hasan, Selim Tarabeah, Eman Shahda, Shadi Awny","doi":"10.1007/s12029-025-01169-0","DOIUrl":"10.1007/s12029-025-01169-0","url":null,"abstract":"<p><strong>Purpose: </strong>Acute kidney injury is a sentinel event affecting colorectal cancer patients either as a consequence of surgery or systemic chemotherapy. It is highly correlated with both short and long-term adverse outcomes. This work aimed to study the prevalence, risk factors, and impact on survival of postoperative (PO-AKI) and post-chemotherapy (PC-AKI) after colorectal cancer (CRC) surgery in Egyptian patients.</p><p><strong>Methods: </strong>Data of the patients with CRC who underwent surgery over the previous 5 years was retrieved from an internet-based medical system. The incidence of PO-AKI and PC-AKI was calculated, the rate and time to resolution of PO-AKI were recorded, and the possible predictors of AKI were assessed using univariate and multivariate analysis; also, the impact of AKI on patients' survival was tested using survival curves.</p><p><strong>Results: </strong>Five hundred sixty-one cases fulfilled the inclusion criteria and were included in the study. PO-AKI was detected in 10.5% of the patients. Significant risk factors included intraoperative hypotension, sepsis, hypoalbuminemia, amount of intraoperative bleeding, neoadjuvant therapy, and preoperative chronic kidney disease (CKD). However, only neoadjuvant treatment (hazard ratio (HR) 2.2) and CKD (HR 3.3) maintained significant risk in the multivariate analysis. PC-AKI was observed in 18.7% of the patients treated. Significant risk factors were previous CKD and the chemotherapy type, mainly affecting those who received Irinotecan-based therapy. The hazard ratio was 8.5 and 2.4 respectively, in multivariate analysis. The overall survival was significantly worse in those who developed PO- or PC-AKI (p < 0.001).</p><p><strong>Conclusion: </strong>AKI affects more than 25% of CRC patients after surgery and/or chemotherapy. Modifiable risk factors include preoperative hypoalbuminemia, intraoperative bleeding, and/or intraoperative hypotension. While, the more important risk factors were non-modifiable including CKD, neoadjuvant therapy, and Irinotecan-containing regimens. Most kidney injuries are stage I; however, they are associated with shorter overall survival.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"45"},"PeriodicalIF":1.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Current Role of Circulating Tumor DNA in the Management of Pancreatic Cancer.","authors":"Madison Cox, Dominic J Vitello, Akhil Chawla","doi":"10.1007/s12029-024-01129-0","DOIUrl":"10.1007/s12029-024-01129-0","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer-related death by 2030. Early identification is rare, with a 5-year overall survival (OS) of less than 10%. Advances in the understanding of PDAC tumor biology are needed to improve these outcomes. Circulating tumor DNA (ctDNA) represents a promising novel biomarker in the identification and management of PDAC. Drawn from peripheral blood and analyzed using a variety of techniques, the detection of ctDNA in PDAC has been associated with shorter OS, minimal residual disease presence, and shorter recurrence-free survival. The use of ctDNA has also been examined as an indicator of therapeutic resistance, susceptibility to targeted therapy, and therapeutic response. While promising, ctDNA analysis is limited by its low rates of detection in some settings and lack of predictive ability in others. Many studies examining the utility of ctDNA for the management of PDAC have been relatively small retrospective cohort studies. The current findings will need to be validated by incorporation of ctDNA analysis into cancer registries and larger prospective studies. Given the current, rapid evolution in the field, it is possible that with time, ctDNA will be more routinely incorporated into the clinical management of PDAC.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"44"},"PeriodicalIF":1.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing of Surgery and Postoperative Outcomes in Esophagectomy for Squamous Cell Carcinoma: A Prospective Study in North India.","authors":"Lovepreet Singh, Cherring Tandup, Manish Thakur, Aravind Sekar, Jayanta Samanta, Satish Subbiah Nagaraj, Swapnesh Kumar Sahu, Yashwant Sakaray, R N Naga Santosh, Kailash Kurdia, Vipul Thakur","doi":"10.1007/s12029-024-01150-3","DOIUrl":"10.1007/s12029-024-01150-3","url":null,"abstract":"<p><strong>Purpose: </strong>Neoadjuvant chemotherapy followed by esophagectomy is the usual approach to manage esophageal squamous cell carcinoma (ESCC). The optimal interval to operate after completion of neoadjuvant chemoradiotherapy (NACRT) still remains controversial.</p><p><strong>Methods: </strong>A prospective study was conducted to observe and compare postoperative complications and pathological outcomes in patients with squamous cell carcinoma of the esophagus who underwent NACRT followed by surgery within 8 weeks or after 8 weeks of NACRT completion. The pathological complete response was assessed using the Mandard tumor regression grade. Morbidity and mortality were compared and were graded using the Clavien-Dindo scale.</p><p><strong>Results: </strong>The study included 50 patients, 19 patients in the < 8-week group and 31 in the > 8-week group study. Patients underwent thoracoscopy-assisted esophagectomy with neoesophagus formation using gastric conduit. There was a significant difference in mortality between the two groups, with three mortalities in the < 8-week group and none in the other group (p = 0.022). Postoperative complications and pathological outcomes did not have a statistically significant difference between the two groups.</p><p><strong>Conclusion: </strong>The pathological response in ESCC cases does not appear to be impacted by the interval between NACRT and surgery; nevertheless, early surgery was associated with a higher risk of mortality.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"43"},"PeriodicalIF":1.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curative-Intended Management of Synchronous Esophageal and Rectal Cancer-A Systematic Literature Review.","authors":"Georg W Wurschi, Claus Schneider, Thomas Ernst, Herry Helfritzsch, Jens Nowatschin, Thomas Bitter, Martin Freesmeyer, Klaus Pietschmann, Maximilian Römer","doi":"10.1007/s12029-025-01170-7","DOIUrl":"10.1007/s12029-025-01170-7","url":null,"abstract":"<p><strong>Purpose: </strong>Synchronous esophageal (EC) and rectal carcinoma (RC) is a rare and challenging condition, particularly in curative-intended treatment. Especially locally advanced tumors may not be suitable for primary resection and require individual multimodal treatment. This review examines curative-intended management of synchronous EC and RC.</p><p><strong>Material and methods: </strong>A systematic literature search across five electronic databases according to the PRISMA guideline was conducted. Individual patient data was analyzed, including two additional cases from our institution.</p><p><strong>Results: </strong>We identified 9 relevant cases from 1552 results. Additionally, two male patients (62 and 65 years old) from our institution were included. Both received 5-fluorouracil/cisplatin-based chemoradiotherapy (CRT) for EC. Sequential short-course radiation (SCRT) for RC was performed in one patient. After complete response (CR) in both tumors, no consecutive surgery was performed. He underwent resection for local recurrence of RC 11 months later and is currently considered as disease-free (30 months follow-up). The second patient underwent primary resection of RC and had early progression following resection of EC. We found that most patients had advanced EC (8/11), with the majority receiving neoadjuvant (5/11) or definitive treatment (3/11). Locally advanced RC was diagnosed in 5/11 patients, primarily treated with sequential resection. Pyrimidine-based systemic treatment was common. Four relapses and two deaths were reported, but median follow-up was 11 (range 1.5-30) months only.</p><p><strong>Conclusion: </strong>The review suggests that neoadjuvant multimodal approaches may offer curative potential for synchronous EC and RC, with individualized treatment protocols adapted from single-cancer protocols. Nevertheless, data on long-term outcome is limited.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"41"},"PeriodicalIF":1.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic Ductal Adenocarcinoma with Medullary Features and a Complete Pathological Response After Neoadjuvant FOLFIRINOX: A Case Report and Literature Review.","authors":"Rodrigo Gomes Taboada, Maria Fernanda Arruda Almeida, Karina Miranda Santiago, Dirce Maria Carraro, Warley Abreu Nunes, Alessandro Landskron Diniz, Tiago Cordeiro Felismino, Victor Hugo Fonseca de Jesus","doi":"10.1007/s12029-024-01140-5","DOIUrl":"10.1007/s12029-024-01140-5","url":null,"abstract":"<p><strong>Purpose: </strong>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor response to chemotherapy. High-frequency microsatellite instability (MSI-H) is a rare biological phenomenon in conventional PDAC, being more frequently described in tumors with medullary or mucinous features.</p><p><strong>Methods and results: </strong>In this manuscript, we report the case of a patient with an MSI-H pancreatic carcinoma with medullary features (medullary carcinoma of the pancreas-MCP) that achieved a complete pathological response after neoadjuvant modified FOLFIRINOX. Additionally, we summarize the available evidence on the clinical, pathological, and molecular features of patients with MCP, along with survival outcomes.</p><p><strong>Conclusions: </strong>MCPs present significant sensitivity not only to immune checkpoint inhibitors, but also to systemic chemotherapy and that the latter treatment modality should not be overlooked. They also present different pathological and molecular features compared with conventional PDAC, meaning they should be considered a separate pathological entity.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"42"},"PeriodicalIF":1.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Prognostic Nomogram for Overall Survival in Gastric Cancer Patients Who Underwent Adjuvant Chemoradiotherapy.","authors":"Melek Tugce Yilmaz, Pervin Hurmuz, Osman Dag, Ecem Yigit, Yasin Ozyurek, Hanife Avci, Mustafa Cengiz","doi":"10.1007/s12029-025-01167-2","DOIUrl":"10.1007/s12029-025-01167-2","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to identify prognostic factors influencing overall survival (OS) in patients with gastric cancer treated with adjuvant chemoradiotherapy (CRT) and to develop a predictive model.</p><p><strong>Methods: </strong>We retrospectively evaluated 245 non-metastatic gastric cancer patients who received adjuvant CRT or radiotherapy from 2010 to 2020. Survival analyses were performed using the Kaplan-Meier method. Prognostic factors were identified through univariate and multivariate Cox regression analyses. A nomogram was constructed based on significant predictive factors for OS, including lymph node ratio, T classification, tumor location, and local recurrence.</p><p><strong>Results: </strong>The median follow-up duration was 41.5 months (range, 6-144.8 months). The 2- and 5-year OS and progression-free survival were 77% and 53% and 64% and 49%, respectively. In multivariate analysis, tumor location (distal vs. proximal), pT classification (pT1-2 vs. pT3-4), lymph node ratio (< 0.18 vs. ≥ 0.18), and presence of local recurrence were independent prognostic factors for OS. The optimal cut-off value for the total nomogram score predicting OS was 116 points. Patients with < 116 points had 2- and 5-year OS rates of 87% and 73%, respectively, compared to 67% and 30% for those with ≥ 116 points.</p><p><strong>Conclusion: </strong>A nomogram was constructed incorporating lymph node ratio, T classification, tumor site, and local recurrence for gastric cancer patients receiving adjuvant CRT. Patients with a total score below 116 demonstrated higher survival rates. This nomogram may aid in defining optimal follow-up intervals.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"39"},"PeriodicalIF":1.6,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nivolumab Combined with Chemotherapy in FGFR2 and PD-L1 Co-Expressing Metastatic Gastric Cancer: A Prospective Phase 2 NIVOFGFR2 Study.","authors":"Ilya Tsimafeyeu, Gunel Musayeva, Samira Mahmudova, Nana Otkhozoria, Bahadur Abbasov, Alisher Kahharov, Fuad Guliyev","doi":"10.1007/s12029-025-01172-5","DOIUrl":"10.1007/s12029-025-01172-5","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy is increasingly significant in treating metastatic gastric cancer. This prospective phase 2 study investigates the efficacy and safety of combining nivolumab with chemotherapy in patients with metastatic gastric cancer co-expressing FGFR2 and PD-L1.</p><p><strong>Methods: </strong>Eligible patients were aged 18 years or older, with previously untreated HER-2 negative, PD-L1 positive, and FGFR2 positive metastatic gastric adenocarcinoma. Patients received nivolumab (360 mg every 3 weeks) in combination with chemotherapy (CAPOX: capecitabine 1000 mg/m² twice daily on days 1-14 and oxaliplatin 130 mg/m² on day 1, every 3 weeks). Tumor assessments were conducted using RECIST v1.1 every 8 weeks for 48 weeks, then every 12 weeks. The primary endpoint was the 1-year progression-free survival (PFS) rate. Secondary endpoints included median PFS, overall survival (OS), objective response rate (ORR), and grade ≥ 3 adverse events (AEs).</p><p><strong>Results: </strong>From June 2022 to October 2023, 194 patients were assessed for eligibility, with 23 patients enrolled and treated. At a median follow-up of 17.3 months, the 1-year PFS rate was 30.4%, with a median PFS of 6.0 months (95% CI, 4.3-7.7). The median OS was 15.1 months (95% CI, 13.2-16.8). The ORR was 21.7%, with one complete response and four partial responses. Grade 3 or higher TRAEs were reported in 34.8% of patients, primarily associated with chemotherapy. No treatment-related deaths occurred.</p><p><strong>Conclusions: </strong>While the primary endpoint of improved 1-year PFS rate was not met, the study offers valuable insights into the potential benefits of combining nivolumab with chemotherapy in FGFR2 and PD-L1 co-expressing metastatic gastric cancer. Future research should optimize patient selection, assess combined immunotherapy and targeted anti-FGFR2 therapy, and further investigate the role of subsequent treatments to maximize therapeutic benefits.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"40"},"PeriodicalIF":1.6,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Novel Targeted Therapies for Pancreatic Adenocarcinoma.","authors":"Tuan Hoang, Erica S Tsang","doi":"10.1007/s12029-024-01149-w","DOIUrl":"https://doi.org/10.1007/s12029-024-01149-w","url":null,"abstract":"<p><strong>Purpose: </strong>Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with limited therapeutic options and poor prognosis. Recent advances in targeted therapies have opened new avenues for intervention in PDAC, focusing on key genetic and molecular pathways that drive tumor progression.</p><p><strong>Methods: </strong>In this review, we provide an overview on advances in novel targeted therapies in pancreatic adenocarcinoma.</p><p><strong>Results: </strong>Here, we explore the latest development in targeting the KRAS pathway, a historically \"undruggable\" target crucial to PDAC pathogenesis. Strategies to inhibit KRAS include direct KRAS-targeted therapies, modulation of upstream and downstream signaling, KRAS-specific siRNA, and novel combination therapies integrating KRAS inhibitors with immune checkpoint blockade, PARP inhibitors, chemotherapy, CDK4/6 inhibitors, and autophagy modulators. Beyond KRAS, emerging targets such as NRG1 fusions, NTRK/ROS1 fusions, RET alterations, and the PRMT5/CDKN2A/MAT2A axis, along with EGFR and Claudin18.2 inhibitors, are also discussed as promising therapeutic strategies. Additionally, the review highlights novel approaches for microsatellite instability-high (MSIH) PDAC and emerging therapies, including adoptive cell therapies (CAR-T, TCR, TIL), cancer vaccines, and strategies to modify the tumor microenvironment.</p><p><strong>Conclusion: </strong>Overall, the rapid evolution of targeted therapies offers renewed optimism in the fight against pancreatic cancer, a malignancy with historically poor outcomes.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"38"},"PeriodicalIF":1.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}