Cancers最新文献

{"title":"The Clinical Outcomes and Safety of Sacituzumab Govitecan in Heavily Pretreated Metastatic Triple-Negative and HR+/HER2- Breast Cancer: A Multicenter Observational Study from Turkey.","authors":"Harun Muğlu, Kaan Helvacı, Bahadır Köylü, Mehmet Haluk Yücel, Özde Melisa Celayir, Umut Demirci, Başak Oyan Uluç, Gül Başaran, Taner Korkmaz, Fatih Selçukbiricik, Ömer Fatih Ölmez, Ahmet Bilici","doi":"10.3390/cancers17091592","DOIUrl":"10.3390/cancers17091592","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Sacituzumab govitecan (SG) is an antibody-drug conjugate targeting Trop-2, approved for use in metastatic triple-negative breast cancer (mTNBC) and more recently in the hormone receptor-positive/HER2-negative (mHRPBC) subtype. While clinical trials have demonstrated its efficacy, real-world data-especially those involving both molecular subtypes-remain scarce. This multicenter, retrospective study aimed to evaluate real-world observational data describing the clinical outcomes, safety, and prognostic factors associated with SG treatment in patients with mTNBC or mHRPBC. <b>Methods:</b> A total of 68 patients treated with SG between 2022 and 2025 were included from multiple oncology centers in Turkey. Patients with mTNBC were required to have received at least one prior chemotherapy line, while mHRPBC patients had received at least two prior chemotherapy lines in addition to cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6) plus hormone therapy. The clinical outcomes-including the progression-free survival (PFS), overall survival (OS), and objective response rate (ORR)-were evaluated. Univariate and multivariate analyses were performed to identify factors influencing outcomes. Adverse events (AEs) were also documented and graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5.0). <b>Results:</b> The cohort included 35 (51.5%) mTNBC and 33 (48.5%) mHRPBC patients. The median PFS was 6.1 months, and the median OS was 12.5 months, with no significant differences between subtypes. The ORR was 52.9%, with a complete response observed in 10.3% of patients. A high Eastern Cooperative Oncology Group Performance Status (ECOG PS) and liver metastasis were independent predictors of poorer PFS and OS. Prior immunotherapy did not negatively impact SG's efficacy. SG was generally well tolerated; the most common AEs were alopecia, anemia, neutropenia, and diarrhea. Treatment discontinuation due to AEs was rare (2.9%). <b>Conclusions:</b> SG was associated with similar clinical outcomes and tolerability in both the mTNBC and mHRPBC subtypes. Although the real-world PFS and OS outcomes mirror those seen in clinical trials, the absence of a control group means that these findings should be interpreted descriptively rather than as confirmation of treatment efficacy. Importantly, this study provides one of the first real-world datasets evaluating SG in the mHRPBC subgroup, highlighting its potential role beyond clinical trials. These results support SG as a valuable therapeutic option in heavily pretreated patients, warranting further prospective and biomarker-driven studies.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival Benefits of GLP-1 Receptor Agonists in Patients with Neuroendocrine Neoplasms: A Large-Scale Propensity-Matched Cohort Study.","authors":"Manal S Fawzy, Awwad Alenezy, Jessan A Jishu, Issa Khan, Ahmad Dessouky, Ahmed Abdelmaksoud, Kristen E Limbach, Eman A Toraih","doi":"10.3390/cancers17091593","DOIUrl":"10.3390/cancers17091593","url":null,"abstract":"<p><p><b>Background:</b> Neuroendocrine neoplasms (NENs) represent a heterogeneous group of malignancies that consist of two major subtypes: neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Glucagon-like peptide-1 receptor agonists (GLP-1Ra) have demonstrated favorable results in preclinical studies, but their impact on NEN outcomes remains unexplored. <b>Methods:</b> Using the TriNetX US Research Network, we identified adult patients with NEN and either diabetes or obesity. After 1:1 propensity score matching based on demographics, comorbidities, procedures, and medication use, we compared survival outcomes between patients who received GLP-1Ra after NEN diagnosis and those who did not. <b>Results:</b> Among 32,464 eligible patients, 3139 received GLP-1Ra and 29,325 did not. After propensity matching, each cohort included 3043 patients with well-balanced baseline characteristics. During follow-up periods extending up to 15 years, all-cause mortality occurred in 356 (11.7%) GLP-1Ra users versus 753 (24.7%) non-users, representing a 13.0% absolute risk reduction (<i>p</i> < 0.001). GLP-1Ra use was associated with significantly improved survival (HR = 0.56, 95%CI = 0.49-0.63, <i>p</i> < 0.001). Both well-differentiated (HR = 0.52) and poorly differentiated tumors (HR = 0.56) showed significant improvement. Among primary sites, lung NENs demonstrated the most pronounced benefit (HR = 0.42). Tirzepatide showed the strongest association with reduced mortality (HR = 0.16), followed by semaglutide (HR = 0.27) and dulaglutide (HR = 0.52). <b>Results:</b> In this large propensity-matched study, GLP-1Ra use was associated with a 44.3% reduction in mortality risk among NEN patients with diabetes or obesity. The magnitude of the observed benefit suggests a potential role for GLP-1Ra as adjunctive therapy in this patient population. Prospective clinical trials are warranted to confirm these findings and explore underlying mechanisms.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geriatric Assessment and Management, Prehabilitation and Rehabilitation for Older Aldults with Non-Colorectal Digestive Cancers.","authors":"Amélie Aregui, Janina Estrada, Madeleine Lefèvre, Anna Carteaux-Taieb, Geoffroy Beraud-Chaulet, Pascal Hammel, Virginie Fossey-Diaz, Thomas Aparicio","doi":"10.3390/cancers17091589","DOIUrl":"10.3390/cancers17091589","url":null,"abstract":"<p><strong>Background: </strong>The incidence of cancer in older patients is high, reaching 2.3 million world-wide in 2018 for patients aged over 80. Because the characteristics of this population make therapeutic choices difficult, co-management between geriatricians and other cancer specialists has gradually become essential.</p><p><strong>Methods: </strong>This narrative review aims to synthesize current data on the contribution of geriatric assessment in the management of elderly patients with non-colorectal digestive cancers. Oncogeriatric assessment is multi-domain, including the evaluation of co-morbidities, autonomy, nutrition, cognition, mood, and functional assessment.</p><p><strong>Results: </strong>Oncogeriatric parameters are predictive of mortality and adverse events. In the peri-operative phase of non-colorectal digestive cancer surgical management, geriatric management can assist in the decision-making process, identify frailties, and arrange a specific and personalized trimodal preoperative rehabilitation program, including nutritional management, adapted physical activity, and psychological care. Its aim is to limit the risks of confusion and of decompensation of comorbidities, mainly cardio-respiratory, which is associated with the highest morbidity in biliary-pancreatic surgery for older adults, facilitate recovery of previous autonomy when possible, and shorten hospital stay. For metastatic cancers, or during multimodal management, such as peri-operative chemotherapy for localized gastric cancers or pre-operative radio-chemotherapy for oesophageal or rectal cancers, specific assessment of the tolerance of chemotherapy is necessary. Neuropathic toxicity and chemobrain have a greater impact on elderly patients, with an increased loss of autonomy. Joint geriatric management can reduce the rate of grade 3-5 adverse effects of chemotherapy in particular and improve quality of life.</p><p><strong>Conclusions: </strong>Co-management between geriatricians and other specialties should be encouraged wherever possible.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling Venetoclax Resistance: Navigating the Future of HMA/Venetoclax-Refractory AML in the Molecular Era.","authors":"Theodora Chatzilygeroudi, Theodoros Karantanos, Vasiliki Pappa","doi":"10.3390/cancers17091586","DOIUrl":"10.3390/cancers17091586","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) has traditionally been linked to a poor prognosis, particularly in older patients who are ineligible for intensive chemotherapy. The advent of Venetoclax, a powerful oral BH3 mimetic targeting anti-apoptotic protein BCL2, has significantly advanced AML treatment. Its combination with the hypomethylating agent azacitidine (AZA/VEN) has become a standard treatment for this group of AML patients, demonstrating a 65% overall response rate and a median overall survival of 14.7 months, compared to 22% and 8 months with azacitidine monotherapy, respectively. However, resistance and relapses remain common, representing a significant clinical challenge. Recent studies have identified molecular alterations, such as mutations in <i>FLT3-ITD</i>, <i>NRAS/KRAS</i>, <i>TP53</i>, and <i>BAX</i>, as major drivers of resistance. Additionally, other factors, including metabolic changes, anti-apoptotic protein expression, and monocytic or erythroid/megakaryocytic differentiation status, contribute to treatment failure. Clinical trials are exploring strategies to overcome venetoclax resistance, including doublet or triplet therapies targeting IDH and FLT3 mutations; novel epigenetic approaches; menin, XPO1, and MDM2 inhibitors; along with immunotherapies like monoclonal antibodies and antibody-drug conjugates. A deeper understanding of the molecular mechanisms of resistance through single-cell analysis will be crucial for developing future therapeutic strategies.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refining Lung Cancer Brain Metastasis Models for Spatiotemporal Dynamic Research and Personalized Therapy.","authors":"Ying Chen, Ao Zhang, Jingrong Wang, Hudan Pan, Liang Liu, Runze Li","doi":"10.3390/cancers17091588","DOIUrl":"10.3390/cancers17091588","url":null,"abstract":"<p><p>Lung cancer brain metastasis (LCBM) is a major contributor to cancer-related mortality, with a median survival of 8-16 months following diagnosis, despite advances in therapeutic strategies. The development of clinically relevant animal models is crucial for understanding the metastatic cascade and assessing therapies that can penetrate the blood-brain barrier (BBB). This review critically evaluates five primary LCBM modeling approaches-orthotopic implantation, intracardiac injection, stereotactic intracranial injection, carotid artery injection, and tail vein injection-focusing on their clinical applicability. We systematically compare their ability to replicate human metastatic pathophysiology and highlight emerging technologies for personalized therapy screening. Additionally, we analyze breakthrough strategies in central nervous system (CNS)-targeted drug delivery, including microparticle targeted delivery systems designed to enhance brain accumulation. By incorporating advances in single-cell omics and AI-driven metastasis prediction, this work provides a roadmap for the next generation of LCBM models, aimed at bridging preclinical and clinical research.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unmet Needs and Their Impact on Quality of Life and Symptoms in Myelodysplastic Neoplasm Patients and Caregivers.","authors":"Elena Crisà, Daniela Cilloni, Marta Riva, Enrico Balleari, Daniela Barraco, Beatrice Manghisi, Lorenza Borin, Michela Calmasini, Anna Calvisi, Isabella Capodanno, Matteo Giovanni Della Porta, Elisa Diral, Bruno Fattizzo, Susanna Fenu, Stefania Paolini, Carlo Finelli, Claudio Fozza, Chiara Frairia, Valentina Giai, Mauro Turrini, Maria Antonia Isoni, Federico Itri, Luca Maurillo, Alfredo Molteni, Giuseppe Alberto Palumbo, Anna Maria Pelizzari, Federica Pilo, Antonella Poloni, Costanza Bosi, Grazia Sanpaolo, Rosaria Sancetta, Cristina Amato, Valeria Santini, Maria Teresa Voso, Sam Salek, Tatyana Ionova, Annamaria Nosari, Esther Natalie Oliva","doi":"10.3390/cancers17091587","DOIUrl":"10.3390/cancers17091587","url":null,"abstract":"<p><strong>Background/objectives: </strong>The aim of this study was to assess the unmet needs of myelodysplastic neoplasm (MDS) patients and their caregivers, focusing on how these needs impact quality of life (QoL) and daily functioning. MDS predominantly affects older adults. It is often complicated by severe red blood cell transfusion-dependent anemia and may require frequent hospital visits, conferring a substantial burden on patients and caregivers.</p><p><strong>Methods: </strong>A national survey was conducted between June 2022 and May 2023 in 46 hematology centers across Italy, involving 259 patients and 105 caregivers. The survey included validated QoL tools (QOL-E and HM-PRO) to measure the impact of disease and treatments on health-related QoL and symptoms.</p><p><strong>Results: </strong>Of the 259 patients surveyed, 42% were transfusion-dependent, with 45% reporting distress related to hospital travel, which was significantly associated with lower QoL scores (QOL-E physical score 50.0 vs. 62.5, <i>p</i> < 0.001). Transfusion dependency led to worse outcomes across physical, emotional, and social domains (HM-PRO Part A score 59.8 vs. 23.7, <i>p</i> < 0.001). Anxiety affected 66% of patients, while 56% reported feeling emotionally distressed. Forty-eight percent of patients required a caregiver, and among caregivers, 29% reported significant disruption to their work, including changing their job or reduced hours. Patients requiring frequent hospital visits showed notably worse QoL scores (HM-PRO emotional score 56.8 vs. 31.8, <i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>This study identified substantial unmet needs for MDS patients, particularly in addressing the heavy burden of transfusions and hospital visits. Both patients and caregivers experienced significant impact on daily life and on QoL, highlighting the urgent need for treatments that reduce hospital dependency, improve patient outcomes, and alleviate the caregiver burden.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Checkpoint Inhibitors and Antibody-Drug Conjugates in Urothelial Carcinoma: Current Landscape and Future Directions.","authors":"Shugo Yajima, Hitoshi Masuda","doi":"10.3390/cancers17091594","DOIUrl":"10.3390/cancers17091594","url":null,"abstract":"<p><strong>Background/objectives: </strong>Urothelial carcinoma (UC) treatment has been transformed by immunotherapy and antibody-drug conjugates (ADCs). This review evaluates the current evidence for these approaches and identifies future directions.</p><p><strong>Methods: </strong>We conducted a structured review of clinical trials, meta-analyses, and guidelines published until early 2025.</p><p><strong>Results: </strong>Immune checkpoint inhibitors have established benefits across multiple settings: post-platinum therapy (pembrolizumab, nivolumab), maintenance therapy (avelumab), adjuvant settings for high-risk muscle-invasive disease (nivolumab), and BCG-unresponsive non-muscle-invasive disease (pembrolizumab). Enfortumab vedotin (targeting Nectin-4) has proven effective in post-platinum/post-immunotherapy. Most significantly, enfortumab vedotin plus pembrolizumab has redefined first-line treatment with unprecedented survival benefits (median OS 31.5 months vs. 16.1 months with chemotherapy; HR 0.47), and nivolumab plus gemcitabine-cisplatin improved outcomes in cisplatin-eligible patients. Key challenges include managing unique toxicity profiles, optimizing treatment sequencing, and developing reliable biomarkers.</p><p><strong>Conclusions: </strong>Combination approaches offer the most promising path forward, with future research needed on resistance mechanisms, biomarker development, and expanding these therapies to earlier disease stages.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Będkowska et al. What We Know and Do Not Yet Know About the Canine Model of Lymphoma in Human Medicine-The Current State of Knowledge. <i>Cancers</i> 2025, <i>17</i>, 596.","authors":"Daria Będkowska, Sara Al-Ameri, Agnieszka Wieczorek, Joanna Bubak, Marta Miszczak","doi":"10.3390/cancers17091590","DOIUrl":"10.3390/cancers17091590","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Role of ADCs in Brain Metastases and Primary Brain Tumors: Insight and Future Directions.","authors":"Francesco Bruzzone, Chiara Barigazzi, Antonio Di Muzio, Isabel Tallarico, Angelo Dipasquale, Agnese Losurdo, Pasquale Persico, Pierina Navarria, Federico Pessina, Armando Santoro, Matteo Simonelli","doi":"10.3390/cancers17091591","DOIUrl":"10.3390/cancers17091591","url":null,"abstract":"<p><p>Primary and secondary brain tumors have always been a challenge due to their high morbidity and poor prognosis. The incidence of brain metastasis is also increasing with the advent of effective new treatments. Traditional systemic treatments have historically had limited success, partly due to poor central nervous system (CNS) penetration. However, the advent in recent decades of new therapies that have shown high encephalic response rates are challenging this paradigm. ADCs represent a new class of compounds revolutionizing cancer treatment with high systemic response rates and lower toxicities. The continuing evolution of ADCs has shown that certain structural features such as payload, linker, and drug-to-antibody ratio (DAR) are essential in determining their efficacy at the encephalic level, and some ADCs have started to exhibit promising efficacy in treating primary and secondary brain tumors. Unfortunately, most patients with untreated encephalic metastases are excluded from clinical trials, with data primarily from retrospective studies or post hoc analyses. This review describes the early signs of ADC efficacy in brain tumors, the role of complementary treatments like radiation therapy, and critical points to improve ADC efficacy in brain malignancies.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12072133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Pancreatic Cancer Using Near-Infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts in Combination with Anticancer Chemotherapeutic Drug.","authors":"Hiroki Yonemura, Masaki Kuwatani, Kohei Nakajima, Atsushi Masamune, Mikako Ogawa, Naoya Sakamoto","doi":"10.3390/cancers17091584","DOIUrl":"10.3390/cancers17091584","url":null,"abstract":"<p><p><b>Background</b>: Pancreatic ductal adenocarcinoma (PDAC), which has a poor prognosis, involves an overabundance of fibroblasts and extracellular matrix. Cancer-associated fibroblasts (CAFs) are critical for providing structural support by secreting soluble factors and extracellular matrix proteins into the stroma. We assessed the potential of near-infrared photoimmunotherapy (NIR-PIT) targeting CAFs in PDAC. <b>Methods</b>: PDAC cells (Capan-1 and SUIT-2) and CAFs (hPSC-5) were used. Anti-human fibroblast activation protein (FAP)/podoplanin (PDPN) antibodies were used to bind to CAFs and conjugates with the specific photosensitizer IRDye^®700DX (IR700) to investigate the effects of NIR-PIT. Thereafter, BALB/c Slc-<i>nu/nu</i> mice were transplanted with Capan-1 and/or CAFs and treated with gemcitabine (GEM) with or without NIR-PIT. <b>Results</b>: The binding rate of anti-FAP antibody-AlexaFluor^®488 conjugate to hPSC-5 cells was high, whereas that of the anti-PDPN antibody-conjugate was not. The incubation of anti-FAP antibody-IR700 conjugate (αFAP-IR700) with hPSC-5 cells for 3 h led to maximal fluorescence on the surface of hPSC-5 cells. When NIR-PIT with αFAP-IR700 was performed in the co-culture group of Capan-1 and hPSC-5 cells, the proliferative capacity of Capan-1 cells decreased to the same level as that when Capan-1 cells were cultured alone (<i>p</i> < 0.05). In vivo, compared with the GEM group, the NIR-PIT with the GEM group showed a significant reduction in the tumor volume (day 28: 79 vs. 382 mm³, <i>p</i> < 0.05). Tumor volumes in the NIR-PIT group were not reduced compared with those in the control group. <b>Conclusions</b>: Combining NIR-PIT with conventional chemotherapy to target CAFs may enhance the anticancer effects on PDAC.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}