Search Results (292)

Gastrointestinal (GI) cancers represent a significant global health burden, with high morbidity and mortality often linked to late-stage detection and metastatic disease. The progression of these malignancies is critically driven by angiogenesis, the formation of new blood vessels, and the surrounding dynamic tumor microenvironment (TME), a complex ecosystem comprising various cell types and non-cellular components. This comprehensive review, based on a systematic search of the PubMed database, synthesizes the existing literature to define the intertwined roles of angiogenesis and the TME in GI tumorigenesis. The TME’s influence creates conditions favorable for tumor growth, invasion, and metastasis, but sometimes induces resistance to current therapies. Available therapeutic strategies for inhibiting angiogenesis involve antibodies and oral tyrosine kinase inhibitors, while immune modulation within the tumor microenvironment is mainly achieved through checkpoint inhibitor antibodies and chemotherapy. Creative emerging strategies encompassing cellular therapies, bispecific antibodies, and new targets such as CD40, DLL4, and Ang2, amongst others, are focused on inhibiting proangiogenic pathways more profoundly, reversing resistance to prior drugs, and modulating the TME to enhance therapeutic efficacy. A deeper understanding of the complex interactions between components of the TME is crucial for addressing the unmet need for novel and effective therapeutic interventions against aggressive GI cancers. Full article

Introduction: Ovarian cancer (OC) is one of the most common gynecologic malignancies and has the highest mortality rate among them. OC has a multifactorial pathogenesis and is characterized by silent onset, progression, and late-stage detection. Therefore, accurate and early detection is of great importance in order to improve survival rates. Emerging evidence reveals that tumor markers are valuable diagnostic and monitoring tools. In this study, we evaluated the aforementioned potential of three markers CA-125, CA 15-3, and serum Calprotectin. CA-125 is a protein that is found elevated in cases of ovarian, breast, and lung cancer. Cancer Antigen 15-3 (CA 15-3) is a protein detected in high levels in women with breast cancer and ovarian cancer and it is significantly elevated in patients with metastasis and recurrence of OC. Calprotectin is a protein released from activated neutrophils, related to inflammatory conditions and can be a potential immune-mediated marker in OC. Purpose: The purpose of this study was to explore the significance of serum calprotectin, CA-125, and CA 15-3 in women diagnosed with serous OC. Methodology: Thirty-eight (38) women with diagnosed OC were included in this research as the study group and twenty-seven (27) healthy women with no history or current diagnosis of OC were included in the control group. Women in both groups shared similar past histories to avoid any other parameters interfering with the study. Our study group was further subdivided into early stage and advanced stage patients. Blood samples were collected from all women of both groups and were examined using ELISA kits to evaluate the levels of the above markers. Results: When comparing patients versus control patients, those with OC exhibited higher levels of Calprotectin compared to healthy individuals. Additionally, Calprotectin showed a statistically significant elevation between the control group and advanced patients. CA-125 remains the current standard of care biomarker exhibiting 90% sensitivity, whereas sensitivities in Calprotectin and CA 15-3 were 60% and 50%, respectively. Conclusions: Serum CA-125 remains the single most valuable biomarker for ovarian cancer, having the highest statistical significance, correlation with disease stage, detecting both early or advanced patients, and sensitivity of 90%. It appears to be a promising inflammatory biomarker in the early diagnosis of ovarian cancer, showing an elevation in patients, while CA 15-3 provides moderate complementary information and exhibits inferior sensitivity when compared to both CA-125 and Calprotectin. The latter appears to be a promising marker and further studies could show if its addition to established protocols could improve early detection, disease progression, or risk stratification. Calprotectin enhances the detection range for ovarian cancer when used alongside CA-125, while this combined approach detected a greater proportion of patients than CA-125 alone, indicating improved diagnostic potential. Full article

Background: Cutaneous squamous cell carcinoma (SCC) is the most common primary malignant tumor of the hand, and its aggressive nature can lead to significant morbidity, particularly when affecting critical structures like the thumb. SCC in this location may arise in the periungual area or the pulp and frequently presents with non-specific symptoms such as swelling, nail deformity, or discharge, features that closely mimic common benign conditions. Methods: A retrospective study analyzed patients with neglected or misdiagnosed SCC of the thumb treated at the Hand and Microsurgery Unit of the Jewish Hospital, Rome, between 2015 and 2025. Patient demographics, duration from symptom onset to diagnosis, initial misdiagnoses, and imaging findings (X-rays, MRI, CT scans, lymph node sonography) were reviewed. Surgical interventions, histopathological grading, and postoperative management were documented, with long-term follow-up focusing on disease progression and patient survival. Results: Sixteen patients were included in the study. The mean age at surgery was 73.6 years (range: 55–93 years), with a mean delay of 8.2 months from symptom onset to diagnosis in 87.5% of cases. Initial misdiagnoses included verruca vulgaris, onychomycosis, paronychia, and osteomyelitis. Imaging consistently revealed soft tissue involvement, bony invasion, and occasional metastasis. Surgical approaches ranged from wide resection to amputation, with thumb reconstruction in selected cases and hand amputation in severe presentations. Long-term follow-up (mean 4.6 years) showed high morbidity, a reduction in hand function and QoL, and a 50% mortality rate, with two cases due to metastatic disease (12.5%). Conclusions: Thumb SCC presents diagnostic and therapeutic challenges, exacerbated by late diagnosis and initial misdiagnoses. Multidisciplinary management involving early recognition, comprehensive imaging, appropriate surgical interventions, and vigilant follow-up is crucial for optimizing outcomes. Full article

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types due to its late diagnosis, low survival rates, and high frequency of metastasis. Considering the molecular mechanism of PDAC development has not been fully elucidated, this study aimed to shed more light on the molecular regulatory signatures of circular RNAs (circRNAs) in PDAC progression and provide a different perspective to identify potential biomarkers as well as discover candidate repositioned drug molecules for the prevention or treatment of PDAC with network-based integrative analysis. The mRNA, miRNA, and circRNA expression profiles of PDAC were obtained from nine microarray datasets. Differentially expressed genes (DEGs), microRNAs (DEmiRNAs), and circular RNAs (DEcircRNAs) were identified. The competing endogenous RNA (ceRNA; DEG–DEmiRNA–DEcircRNA) regulatory network was constructed, which included 12 DEcircRNAs, 64 DEGs, and 6 miRNAs specific to PDAC. The ADAM12, MET, QKI, SEC23A, and ZEB2 were identified as hub genes and demonstrated significant survival probability for PDAC. In addition to providing novel biomarkers for diagnosis that can be detected non-invasively, the secretion levels of hub genes-associated proteins were found in plasma, serum, and oral epithelium. The drug repositioning analysis revealed vorinostat, meclocycline sulfosalicylate, and trichostatin A, which exhibited significant binding affinities to the hub genes compared to their inhibitors via molecular docking analysis. Full article

Purpose: We present our single-institution experience of sarcomatous brain metastasis patients who underwent stereotactic radiosurgery (SRS) over the past 35 years. Methods: In total, 31 patients (16 males) who underwent SRS for sarcoma brain metastases were identified. Median age at presentation to SRS was 47 (range: 4–78) months. Common histopathologies included leiomyosarcoma (eight patients), osteosarcoma (six patients), alveolar sarcoma (three patients), Ewing sarcoma (three patients), and undifferentiated/unclassified sarcoma (three patients). The median Karnofsky Performance Score (KPS) was 90. Nine patients underwent pre-SRS craniotomy. The median dose prescribed was 18 Gy. The median cumulative tumor volume was 1.4 cc. Results: Median patient overall survival (OS) after SRS was 7 (range: 0–155) months. Local tumor control (LTC) was achieved in 105 out of 113 tumors, at a median time of 3 (range: 0–17) months between SRS and progression. LTC rates per patient and per tumor were 74.2% and 92.9%, respectively. Following SRS, 10 patients (32.3%) developed new tumors at a median time of 6 (range: 1–25) months. Four patients experienced adverse radiation effects (AREs). At the last follow-up, all patients died, one patient from intracranial progression, 27 from systemic disease progression, and the remaining from unrelated medical conditions. Conclusions: Given high LTC and low ARE rates, this suggests SRS as a strong candidate for the non-invasive management of sarcomatous brain metastases, which typically present late following initial presentation of the primary disease. Full article

Pancreatic cancer is characterized by late diagnosis, therapy resistance, and poor prognosis, necessitating the exploration of early carcinogenesis and prevention methods. Preclinical mouse models have evolved from cell line-based to human tumor tissue- or organoid-derived xenografts, now to humanized mouse models and genetically engineered mouse models (GEMMs). GEMMs, primarily driven by oncogenic Kras mutations and tumor suppressor gene alterations, offer a realistic platform for investigating pancreatic cancer initiation, progression, and metastasis. The incorporation of inducible somatic mutations and CRISPR-Cas9 screening methods has expanded their utility. To better recapitulate tumor initiation triggered by inflammatory cues, common pancreatic risk factors are being integrated into model designs. This approach aims to decipher the role of environmental factors as secondary or parallel triggers of tumor initiation alongside oncogenic burdens. Emerging models exploring pancreatitis, obesity, diabetes, and other risk factors offer significant translational potential. This review describes current mouse models for studying pancreatic carcinogenesis, their combination with inflammatory factors, and their utility in evaluating pathogenesis, providing guidance for selecting the most suitable models for pancreatic cancer research. Full article

Background: The mechanical conditioning (MeCo) score is a multigene expression signature that is acquired by cancer cells in the primary breast tumor and is reflective of their responsiveness to ECM stiffness caused by tumor fibrosis. Chromatin remodeling downstream of mechanotransduction allows cancer cells to retain these acquired aggressive features even in the absence of mechanical stimulation from the primary tumor microenvironment, for instance, after dissemination through systemic circulation during metastasis. Importantly, patients who have high MeCo score tumors are at higher risk of developing metastatic breast cancer, compared to those with low MeCo scores. Moreover, circulating tumor cells (CTCs) are associated with a higher rate of metastatic dissemination, making CTC detection in the circulation of patients with breast cancer a significant prognostic biomarker for breast cancer metastasis. Beyond their enumeration per blood volume units, specific prognostic features of CTCs are not fully explored. We sought to determine whether MeCo scores increase stepwise along the metastatic cascade, from primary tumors to CTCs to distant metastatic colonization, using patient-matched biopsies. Methods: CTCs were isolated from the peripheral blood of two patient cohorts: patients with early-stage breast cancer using immunomagnetic enrichment/FACS methodology; and patients with late-stage breast cancer using the ANGLE Parsortix microfluidics system. Gene expression profiling using RNA-seq was performed on CTCs and matched primary tumors (PTs) in the early-stage cohort, and on CTCs and matched metastases (METs) for the late-stage cohorts. A quantile normalization approach was used to allow comparison across cohorts and MeCo scores were computed for all samples. The Wilcoxon matched-pairs signed rank test was performed for the comparison of MeCo scores from matching samples within each cohort; the Mann–Whitney unpaired test was used to compare MeCo scores of CTCs across cohorts. Results: In 12 pairs of patients with early-stage breast cancer, MeCo scores in CTCs were significantly higher than in their matched PTs (p = 0.026). Additionally, in 26 pairs of metastatic patient CTCs and METs, MeCo scores were significantly higher in METs compared to matched CTCs (p = 0.0004). MeCo scores of CTCs were similar between patients with early- and late-stage breast cancers, despite differing CTC isolation strategies (epitope-dependent and microfluidics size gradient). Notably, 98% of the genes in the MeCo score were present across evaluable CTC, MET, and PT samples. Conclusions: Our results show that the MeCo score is higher in CTCs than in PTs, and higher in METs compared to CTCs, in early- and late-stage breast cancer, respectively (i.e., PT < CTC < MET). Therefore, the MeCo score is progressively higher throughout the metastatic cascade in breast cancer. These findings demonstrate that mechanical conditioning from primary tumors is retained during metastatic progression, after mechanical induction by ECM stiffness is lost, as cancer cells disseminate through systemic circulation. Additionally, these findings support that cancer cells with higher MeCo scores are more competent with—and potentially selected for—metastatic progression. Importantly, these findings provide a novel feature of CTCs, mechanical conditioning (MeCo), which is associated with higher capacity for metastasis. Furthermore, since the CTC MeCo score is elevated even in early-stage breast cancer, it could provide, in addition to CTC enumeration, a potential prognostic indicator to improve metastatic risk assessment in early disease. Full article

Background: Extramammary Paget’s disease (EMPD) is a rare cutaneous carcinoma that typically affects the elderly and is frequently observed in genital and perianal regions. We analyzed the outcomes and prognostic factors for EMPD after radiation therapy (RT). Methods: We analyzed data from 81 patients with non-metastatic EMPD who received either RT alone or in combination with surgery and/or chemotherapy. The median radiation dose was 56 Gy in 28 fractions. Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using the Kaplan–Meier method. Multivariate analyses were performed using the Cox proportional hazards model. Late adverse events were evaluated by NCI-CTCAE version 5.0. Results: The median age was 78 years, and the median follow-up period was 36 months. The three-year LC, PFS, and OS rates were 75%, 52%, and 80%, respectively. Multivariate analyses identified the presence of lymph node (LN) metastasis, the absence of surgery, and the omission of elective nodal irradiation (i.e., local irradiation only) as significant factors for unfavorable LC (p = 0.01, 0.02, and 0.006) and PFS (p = 0.001, 0.04, and 0.03). LN metastasis was also a significant factor for unfavorable OS (p = 0.005). One patient developed grade 2 skin infection, and another developed grade 3 lymphedema; no grade 4 or higher toxicity was observed. Conclusions: The present results revealed prognostic factors for EMPD after RT and suggest that the absence of surgery and omission of elective nodal irradiation worsened outcomes. A prospective study is needed to establish an optimal treatment strategy for this rare malignancy, which is common in the elderly. Full article

Background: Transoral robotic surgery (TORS) is a minimally invasive procedure that is performed with neck dissection (ND) and postoperative radiotherapy when necessary. This study aimed to review the methods of vascular ligation and ND in cases of TORS for oropharyngeal cancer in Japan. Methods: We enrolled 44 consecutive patients who underwent TORS for laryngopharyngeal cancer between December 2019 and December 2023. Of these, 35 patients who underwent TORS as a first-line treatment for oropharyngeal cancer were included in this study. We retrospectively collected patient data on age, sex, primary tumor location, clinical tumor–node classification, Eastern Cooperative Oncology Group performance status, history of irradiation to the neck, presence of anticoagulants, pathological results, tumor size, total operative duration, console time, length of skin incision operative result, estimated blood loss, late cervical lymph node metastasis, perioperative complications, postoperative hospital stay, postoperative bleeding, period until oral intake after surgery, and swallowing function. Intra- and postoperative outcomes of TORS, TORS + ND (IIa) + vascular ligation, and TORS + ND (II–IV) + vascular ligation. Results: Significant differences were found in operative duration, blood loss during ND, and skin incision length between TORS + ND (IIa) + vascular ligation and TORS + ND (II–IV) + vascular ligation. Console time and blood loss did not significantly differ between the two groups. Each group contained one case of postoperative bleeding. Conclusions: Safe and minimally invasive treatments can be established if vascular ligation and ND are implemented based on appropriate case selection. Full article

Background/Objectives: Clear cell sarcoma (CCS) is a very uncommon, aggressive soft-tissue sarcoma (STS) with a dismal prognosis. In the current literature, there are very limited data focused on the radiological features of CCS. Our study’s objective was to describe CCS pre-treatment’s peculiar imaging characteristics (MRI above all) and to assess if some radiologic features may predict patients’ outcomes with regard to the occurrence of distant metastases. Methods: Our single-center experience includes all the patients with a histological diagnosis of CCS and available radiological and clinical data: 14 patients (8M, 6F, mean age 39.4 years old) were included. The available pre-treatment MRI or contrast-enhanced computed tomography (CECT) studies were examined using an analytical grid that incorporated characteristics from the most recent STS research. The occurrence of metastatic disease was matched with radiological features from baseline imaging studies. Results: MRI was available in 13 patients and CECT in 1 patient. The mean longest diameter (LD) was 50.5 mm ± 29.2. In 10 cases (71.4%), the tumor was deeply seated. MRI revealed a slightly high signal intensity (SI) on T1-WI and a high SI on T2-WI in every subject. At baseline, metastases were already present in 5/14 (35.7%) patients, 3 more developed metastases during the following 5 years (8/14, 57.1%), and 2 additional developed late-onset metastasis after more than 5 years from the diagnosis (total of 10/14 metastatic patients 71.4%). LD and metastasis at diagnosis were significantly correlated (Pearson correlation = 72%, p-value = 0.004). A pre-treatment LD > 4 cm was significantly associated with the development of distant metastases within 5 years from diagnosis and in subsequent follow-up (p = 0.0003). LD > 4 cm represents an increase in risk of metastatic disease within 5 years and during the course of follow-up (OR = 195.00, 95%CI: 3.36–11285.55, p = 0.01). The presence of MRI signs of macroscopic necrosis represented an increase in risk of metastatic disease within 5 years (OR = 15.00, 95%CI: 1.03–218.31—p = 0.04). Conclusions: The identification of MRI features of aggressive biology is a key element for an early referral to sarcoma centers. In our study, a LD > 4 cm and the presence of MRI signs of macroscopic necrosis at the baseline images resulted in being a predictor of metastatic disease. Full article

Background: Primary malignant bone tumors are exceedingly rare, with an incidence of 0.5 to 1 per million, and sacral localization is even more uncommon, representing only 1–3.5% of these tumors. These malignancies are often diagnosed late due to their asymptomatic nature until they present as large, advanced intrapelvic tumors. Management is complicated by the need for precise surgical intervention and the consideration of adjuvant therapies based on tumor histology and patient factors. Methods: We conducted a single-center, retrospective analysis of patients who underwent complete, partial, or hemisacrectomy for primary malignant bone tumors or recurrent sacral metastases. Excluded were patients with metastatic disease not necessitating sacrectomy. Data collected included demographics, clinical characteristics, tumor types, resection status, adjuvant therapies, recurrence, metastasis, and complications. Surgical approaches were categorized as posterior, anterior, or combined anterior–posterior. The primary outcomes were overall survival and disease-free survival, while the secondary outcomes focused on complication rates and functional outcomes. Results: The study included 19 patients (7 females, 12 males) with a mean age of 48.9 years at the time of surgery. Primary malignancies were present in 90% of patients. Surgical approaches varied: 20% underwent double access and 5% anterior access only, and the remainder had posterior approaches. High partial sacrectomy (above S3) was performed in 20%, while low sacrectomy (at or below S3) was performed in 80%. Complete resection with clean margins (R0) was achieved in 65% of cases, while 35% had R1 resections with microscopic tumor remnants. Root resection was necessary in 25% of patients. Local recurrence occurred in 25% of patients, with two requiring reoperation and neurological sacrifice. Distant metastases were observed in 20% of cases. Postoperative complications affected 60% of patients. The most common issues were surgical wound dehiscence with delayed healing (35%) and visceral changes affecting the bowel and urination (25%). No mechanical complications were reported. Conclusions: Sacrectomy remains a challenging procedure with substantial morbidity and variability in outcomes. The choice of surgical approach—posterior, anterior, or combined—depends on tumor location and extent. While posterior-only approaches are often preferred for lower sacral lesions, combined approaches may be necessary for more extensive tumors. Survival and disease-free survival rates are influenced by resection margins and the biological behavior of the tumor. Wide-margin resections (R0) are associated with lower local recurrence rates but do not eliminate the risk of distant metastases. Full article

Background: The heterogeneity of sarcomas and resulting distinct sub-type specific characteristics, their high recurrence rates, and tendency for distant metastasis, continue to present significant challenges to providing optimal treatments. Objective: To provide a comprehensive review of current literature and clinical trials in gene and cell therapies for sarcomas. Methods: A comprehensive literature search was conducted utilizing the following databases: PubMed, Medline, Google Scholar and clinicaltrials.gov. Search terms included “gene therapy”, “cell therapy”, “NK cell therapy, “CAR-T therapy”, “virotherapy”, “sarcoma”, “gene therapy”, and “solid tumors”. Additional sources were identified through manual searching for references of relevant studies. No language restrictions were set. The NCT number, study status, condition, and phase were noted for clinical trials. Results: There are only three gene and cell therapies for sarcomas that have been approved by a federal regulatory agency. Rexin-G: the first tumor-targeted gene therapy vector designed to target all advanced solid malignancies, including chemo-refractory osteosarcomas and soft tissue sarcomas, was approved by the Philippine FDA in 2007. Gendicine was the first oncolytic virus approved for intratumoral delivery in China in 2003. Afami-cel, an innovative chimeric antigen receptor (CAR) T cell therapy, was approved for synovial sarcoma in the United States in 2024. Other promising therapies are discussed in the text. Conclusions: The future of gene and cell therapy for sarcomas holds great promise, as research moves to late-stage clinical development. The integration of gene and cell therapies into standard sarcoma treatment protocols has the potential to significantly improve the quality of life and outcomes for patients with this rare and challenging group of cancers. Full article

Cancer remains a significant global health challenge, necessitating novel therapeutic interventions. Clerodendrum chinense leaf extract (CCL) has gained interest for its potential anticancer properties due to its bioactive composition. This study aims to evaluate the cytotoxic effects of CCL against MCF-7 breast cancer and HeLa cervical cancer cells and elucidate its mechanisms of action. High-performance liquid chromatography identified verbascoside, isoverbascoside, and hispidulin as the major bioactive compounds. CCL exhibited time- and dose-dependent cytotoxicity, with MCF-7 cells showing greater sensitivity (IC₅₀ = 126.8 µg/mL, 72 h) than HeLa cells (216.1 µg/mL, 72 h). Flow cytometry confirmed apoptotic induction, with late apoptosis increasing at moderate concentrations (16.03–23.55%) and necrosis prevailing at higher doses (50.80–63.68%). Reactive oxygen species generation was significantly elevated in MCF-7 (70.2%) and HeLa (60.4%) cells at 250 µg/mL. CCL effectively suppressed colony formation and cell migration in a dose-dependent manner. Molecular docking studies demonstrated that apoptosis induction of CCL bioactive compounds may mediate through the pro-apoptotic BCL2 associated X, apoptosis regulator (BAX) regulator. These findings highlight the potential of CCL as a natural anticancer agent with multiple mechanisms, including reactive oxygen species (ROS)-induced apoptosis, BAX activation, and inhibition of proliferation and metastasis. Full article

Background/Objectives: Immunotherapy has shown promising results in some cancers, but its efficacy remains limited in pancreatic ductal adenocarcinoma (PDAC). Vaccines in nanoparticle form (nanovaccines) can incorporate immunostimulating components to induce a potent immune response. As mesothelin (MSLN) is a tumor-associated antigen overexpressed in PDAC, we evaluated the effect of MSLN nanovaccine in a syngeneic orthotopic KPC-PDAC mouse model. Methods: An MSLN peptide combining three MSLN epitopes and two adjuvants, poly I:C and R848, was encapsulated in PLGA–chitosan nanoparticles to generate the nanovaccine. Results: The MSLN nanovaccine was successfully taken up by dendritic cells in vitro and was found in inguinal lymph nodes 24 h after subcutaneous injection into C57BL/6 mice. Nanovaccine re-stimulation of splenocytes from vaccinated mice led to increased levels of interferon-γ in vitro compared to unstimulated splenocytes. Higher levels of MSLN-specific IgM and IgG antibodies were detected in the serum of vaccinated mice compared to that of control mice. Three vaccination regimens were tested: a prophylactic scheme that included vaccination before tumor induction and two therapeutic schemes involving early and late vaccination after tumor cell inoculation. MSLN nanovaccination inhibited KPC tumor progression and metastasis and induced higher CD8⁺ T cell infiltration in the tumor that developed in response to prophylactic and early therapeutic schedules but not in response to a later vaccination approach. Although the nanovaccine treatment elicited higher humoral and cellular antigen-specific responses in tumor-bearing mice for both vaccination strategies, the therapeutic vaccination also increased the expression of exhaustion markers in CD8⁺ T cells. Conclusions: Our results support the relevance of an MSLN-based nanovaccine as a new immunotherapy treatment for PDAC and propose an innovative method of vaccine delivery using NPs. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is diagnosed at a late stage with distant metastasis in an overwhelming 50% of cases, and the prognosis is poor. Treating this extremely aggressive disease with standard-of-care therapies has led to modest benefits in overall survival, mainly due to a lack of targeted early treatment modalities, as early detection has not yet been possible. Mucin-16 (MUC16) is a glycoprotein overexpressed in more than 60% of patients with PDAC and is a tumor-specific biomarker. Methods: In this study, a magnetic resonance imaging (MRI) probe to facilitate the detection of early and late lesions of PDAC is developed by conjugating a MUC16-targeted humanized antibody (huAR9.6) with gadolinium. Results: In preclinical mouse models, this MUC16-targeted MRI probe demonstrates effective contrast enhancement in early lesions of PDAC in the subcutaneous setting and allows for the detection of late-stage pancreatic cancer tumors in an orthotopic model. The probe did not induce any toxicity in vital organs at the administered doses. Conclusions: This study establishes that synthesizing a MUC16-targeted MRI probe is feasible and allows for the better high-resolution contrast enhancement of MUC16+ PDAC lesions to facilitate detection and possibly better treatment strategies. Full article