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Novel Diagnosis and Treatment Approaches in Pancreatic Cancer

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 13166

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Special Issue Editor

Prof. Dr. Atsushi Masamune

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Guest Editor

Division of Gastroenterology, Graduate School of Medicine Sendai, Tohoku University, Sendai, Japan
Interests: molecular mechanisms of pancreatic diseases; pancreatic fibrosis; biomarkers; genetics of pancreatic diseases; epidemiology
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Special Issue Information

Dear Colleagues,

Pancreatic cancer still remains intractable due to difficulty in early diagnosis, its rapid progression, and its resistance to conventional therapy. To overcome these difficulties, multidisciplinary approaches including the development of novel diagnosis and treatment approaches are urgently needed. Recently, we have seen progress in the early diagnosis of pancreatic cancer such as the risk-factor stratification of new-onset diabetes mellitus, the development of microRNA-based biomarkers and cell-free DNA, and the identification of rather specific imaging findings. Regarding treatments, the efficacy of neoadjuvant chemotherapy has been proven, drugs that disrupt the tumor–stromal compartment might be useful for improved drug delivery, and targeted agents based on genetic testing such as PARP inhibitors for BRCA pathway-deficient pancreatic cancer and immune checkpoint inhibitors have shown promising results.

In this Special Issue, we will share up-to-date research findings in this field. Articles dealing with a wide range of novel diagnosis and treatment approaches in pancreatic cancer are welcome. Examples include, but are not limited to, the early diagnosis of pancreatic cancer based on risk factors, novel biomarkers, and imaging modalities including artificial intelligence. Basic, translational, and clinical research papers are all welcome.

Prof. Dr. Atsushi Masamune
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

pancreatic cancer
pancreatic fibrosis
biomarker
risk factor
genetic testing
artificial intelligence
endoscopic ultrasound
stroma
cancer-associated fibroblasts
familial pancreatic cancer

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Published Papers (6 papers)

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Research

Jump to: Review, Other

15 pages, 1358 KB

Open AccessArticle

Comparison of Comprehensive Serum miRNA Sequencing and Apolipoprotein A2 Isoforms for Early Detection of Pancreatic Cancer

by Hirotaka Kashima, Munenori Kawai, Kei Iimori, Munemasa Nagao, Takamitsu J. Morikawa, Ryo Otomo, Mitsuharu Hirai, Kosuke Minaga, Masanori Asada, Atsushi Umemura, Yoshito Uenoyama, Toshihiro Morita, Shujiro Yazumi, Ryuki Minami, Saiko Marui, Yuki Yamauchi, Yoshitaka Nakai, Yutaka Takada, Seiji Shio, Takuto Yoshioka, Naoki Kanda, Tomonori Masuda, Kazuyuki Nagai, Etsuro Hatano, Akihisa Fukuda and Hiroshi Seno Show full author list Hide full author list

Cancers 2026, 18(7), 1177; https://doi.org/10.3390/cancers18071177 - 7 Apr 2026

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Abstract

Backgrounds and Aim: Pancreatic cancer is frequently diagnosed at advanced stages, highlighting the need for biomarkers that are capable of detecting early-stage disease in asymptomatic individuals. Recently, apolipoprotein A2 isoforms (ApoA2-ATQ/AT) have been reported as a new blood biomarker for pancreatic cancer. We recently developed diagnostic models based on 100 highly expressed serum microRNAs (miRNAs) combined with CA19-9; these models achieved high accuracy in terms of distinguishing individuals with pancreatic cancer from healthy individuals. This study aimed to compare the diagnostic performance of these miRNA-based models with that of the ApoA2-ATQ/AT biomarker. Methods: Comprehensive sequencing of serum miRNAs was conducted using samples from 120 pancreatic cancer patients recruited across 14 hospitals, along with 93 healthy controls without cancer. Serum CA19-9 levels, miRNA index values, miRNA+CA19-9 index values, and ApoA2 index values were assessed. miRNA-based indices were derived from classification models built on an automated machine-learning platform. Results: The miRNA model (AUC 0.94; 95% CI 0.91–0.97) and the miRNA+CA19-9 model (AUC 0.99; 95% CI 0.98–1.00) outperformed ApoA2 (AUC 0.89; 95% CI 0.84–0.93) in terms of distinguishing individuals with pancreatic cancer from healthy controls across all stages. In early-stage disease (stages 0–I and 0–II), both miRNA-based models also demonstrated superior performance. Strong negative correlations were observed between the ApoA2 index and both the miRNA model index (r = −0.62) and the miRNA+CA19-9 index (r = −0.63). Conclusions: These findings suggest that miRNA-based diagnostic models, particularly when combined with CA19-9, could serve as powerful tools for the early detection of pancreatic cancer. Full article

(This article belongs to the Special Issue Novel Diagnosis and Treatment Approaches in Pancreatic Cancer)

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Review

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15 pages, 776 KB

Open AccessReview

Liquid Biopsy for Early Pancreatic Cancer Detection: Why Has It Not Yet Worked?

by Kenji Takahashi, Yusuke Ono, Kenzui Taniue, Krushna C. Patra, Takuya Yamamoto, Mikihiro Fujiya and Yusuke Mizukami

Cancers 2026, 18(3), 525; https://doi.org/10.3390/cancers18030525 - 5 Feb 2026

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Abstract

Despite extensive technological advances and an ever-growing body of literature, liquid biopsy has yet to achieve reliable early detection of pancreatic ductal adenocarcinoma (PDA). Numerous studies have investigated circulating tumor-derived components, including cell-free DNA (cfDNA), cell-free RNA (cfRNA), extracellular vesicles (EVs), and circulating tumor cells (CTCs), primarily using peripheral blood samples; however, their clinical utility for early-stage disease remains limited. The fundamental obstacles are biological rather than purely technical: early PDA and its precursor lesions, such as pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMN), are characterized by minimal tumor burden, low levels of nucleic acid shedding, and substantial background signals from non-neoplastic tissues. Increasing analytical complexity through multilayered liquid biopsy approaches, including analyses from pancreas-associated fluid, has not consistently translated into improved diagnostic performance and, in some cases, has amplified issues related to specificity, reproducibility, and interpretability. Moreover, molecular alterations detected in body fluids may reflect clonal expansion without inevitable malignant progression, raising concerns regarding overdiagnosis and clinical decision-making. Pre-analytical variability, lack of standardization, and limited access to tumor-adjacent fluids further hinder clinical implementation. Liquid biopsy should therefore be regarded as a complementary modality rather than a substitute for histopathological diagnosis, with its precise clinical role in early detection still ill-defined. In this review, we critically examine why liquid biopsy has not yet succeeded in early PDA detection, highlighting the key biological, technical, and clinical barriers that must be addressed to move the field beyond exploratory research toward meaningful clinical application. Full article

(This article belongs to the Special Issue Novel Diagnosis and Treatment Approaches in Pancreatic Cancer)

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16 pages, 1316 KB

Open AccessReview

Emergent Role of Intra-Tumor Radioactive Implantation in Pancreatic Cancer

by Pathipat Durongpongkasem, Amanda H. Lim and Nam Q. Nguyen

Cancers 2026, 18(2), 302; https://doi.org/10.3390/cancers18020302 - 19 Jan 2026

Viewed by 756

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited treatment options for patients with locally advanced or metastatic disease. Endoscopic ultrasound (EUS)-guided intra-tumoral radioactive implantation has emerged as a minimally invasive approach to enhance local tumor control while minimizing systemic toxicity. Among the available isotopes, phosphorus-32 (³²P) microparticle brachytherapy has demonstrated promising outcomes, including significant tumor regression, reductions in CA 19-9, and higher rates of tumor downstaging and surgical conversion when combined with systemic chemotherapy. Compared with stereotactic body radiotherapy (SBRT), ³²P delivers higher intratumoral radiation doses, spares adjacent healthy tissues, and can be administered during ongoing chemotherapy without treatment interruption. Additionally, preliminary evidence suggests that ³²P may modulate the tumor microenvironment, improving vascularity and enhancing chemotherapy efficacy. The procedure shows high technical success and a favorable safety profile, with minimal serious adverse events. Future directions include prospective randomized trials to validate its impact on survival, optimize dosing, and establish treatment protocols. EUS-guided intra-tumoral ³²P brachytherapy holds potential as a key component of multimodal therapy, bridging local tumor control and systemic disease management in PDAC. Full article

(This article belongs to the Special Issue Novel Diagnosis and Treatment Approaches in Pancreatic Cancer)

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22 pages, 1524 KB

Open AccessReview

Strategies to Target the Tumor-Associated Macrophages in the Immunosuppressive Microenvironment of Pancreatic Ductal Adenocarcinoma

by Ryu Matsumoto, Kiyonori Tanoue, Chieri Nakayama, Masashi Okawa, Yuto Hozaka, Tetsuya Idichi, Yuko Mataki and Takao Ohtsuka

Cancers 2025, 17(18), 3090; https://doi.org/10.3390/cancers17183090 - 22 Sep 2025

Viewed by 3350

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a critical disease requiring the development of novel effective therapeutic approaches due to its increasing global incidence and associated low survival rates. While immunotherapy, including immune checkpoint inhibitors, has shown efficacy against various tumors, developing an effective treatment approach for PDAC poses a challenge. This is primarily attributed to the complex and distinctive immune evasion mechanisms of PDAC. Recent studies have revealed that tumor-associated macrophages (TAMs) play a crucial role in enhancing immune evasion in PDAC. This role is mediated through multiple pathways, including cytokine secretion and the activation or suppression of diverse immune cells. A clear understanding of how macrophages contribute to PDAC proliferation could lead to the development of novel immune therapy approaches targeting TAMs. In this review, we summarized the multifaceted activities and roles of TAMs in PDAC and explored the potential effect of immunotherapeutic approaches on PDAC, with a particular focus on chimeric antigen receptor (CAR) macrophages. This review was based on promising findings from recent studies on CAR macrophage-based immunotherapy for solid tumors. Full article

(This article belongs to the Special Issue Novel Diagnosis and Treatment Approaches in Pancreatic Cancer)

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21 pages, 561 KB

Open AccessReview

Postoperative Acute Pancreatitis After Pancreatic Resections—A Narrative Review and a Diagnostic Algorithm

by Ewa Grudzińska and Magdalena Gajda

Cancers 2025, 17(17), 2773; https://doi.org/10.3390/cancers17172773 - 26 Aug 2025

Viewed by 3711

Abstract

Pancreatic cancer is one of the deadliest tumors, and surgery is, for now, the only potentially curative treatment. However, pancreatic surgery is burdened with severe complications, of which postoperative pancreatic fistula (POPF) is one of the most dangerous. Recent publications show that there is a strong connection between POPF and postoperative acute pancreatitis (POAP). In this review, we present the available literature on PPAP, summarizing the available diagnostic, prophylactic, and treatment tools. We identify POAP as a specific postoperative complication where a lack of unified definitions and treatment guidelines makes both research and clinical decisions more difficult. Based on the available studies, we also propose an algorithm for early POAP detection. Full article

(This article belongs to the Special Issue Novel Diagnosis and Treatment Approaches in Pancreatic Cancer)

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Other

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36 pages, 606 KB

Open AccessSystematic Review

Failure to Rescue After Surgery for Pancreatic Cancer: A Systematic Review and Narrative Synthesis of Risk Factors and Safety Strategies

by Masashi Uramatsu, Yoshikazu Fujisawa, Paul Barach, Hiroaki Osakabe, Moe Matsumoto and Yuichi Nagakawa

Cancers 2025, 17(19), 3259; https://doi.org/10.3390/cancers17193259 - 8 Oct 2025

Cited by 3 | Viewed by 2724

Abstract

Background: Failure to rescue (FTR), defined as death after major postoperative complications, is a critical quality indicator in pancreatic cancer surgery. Despite advances in surgical techniques and perioperative care, FTR rates remain high and vary across institutions. Methods: This systematic review uses a narrative synthesis followed by PRISMA 2020. A PubMed search (1992–2025) identified 83 studies; after screening, 52 studies (2010–2025) were included. Eligible designs were registry-based, multicenter, single-center, or prospective audits. Given substantial heterogeneity in study designs, FTR definitions, and outcome measures, a narrative synthesis was performed; no formal risk-of-bias assessment or meta-analysis was conducted. Results: Definitions of FTR varied (in-hospital, 30-day, 90-day, severity-based, and complication-specific cases). Reported rates differed by definition: average reported rates were 13.2% for 90-day CD ≥ III (G1); 10.3% for in-hospital/30-day CD ≥ III (G3); and 7.4% for 30-day “serious/major” morbidity (G8). Absolute differences were +3.0 and +2.9 percentage points (exploratory, descriptive comparisons). Five domains were consistently associated with lower FTR: (i) centralization to high-volume centers; (ii) safe adoption/refinement of surgical techniques; (iii) optimized perioperative management including early imaging and structured escalation pathways; (iv) patient-level risk stratification and prehabilitation; and (v) non-technical skills (NTSs) such as decision-making, situational awareness, communication, teamwork, and leadership. Among NTS domains, stress and fatigue management were not addressed in any included study. Limitations: Evidence is predominantly observational with substantial heterogeneity in study designs and FTR definitions; the search was limited to PubMed; and no formal risk-of-bias, publication-bias assessment, or meta-analysis was performed. Consequently, estimates and associations are descriptive/associative with limited certainty and generalizability. Conclusions: NTSs were rarely used or measured across the included studies, with validated instruments; quantitative assessment was uncommon, and no study evaluated stress or fatigue management. Reducing the FTR after pancreatic surgery will require standardized, pancreas-specific definitions of FTR, process-level rescue metrics, and deliberate strengthening of NTS. We recommend a pancreas-specific operational definition with an explicit numerator/denominator: numerator = all-cause mortality within 90 days of surgery; denominator = patients who experience major complications (Clavien–Dindo grade III–V, often labeled “CD ≥ 3”). Addressing the gaps in stress and fatigue management and embedding behavioral metrics into quality improvement programs are critical next steps to reduce preventable mortality after complex pancreatic cancer procedures. Full article

(This article belongs to the Special Issue Novel Diagnosis and Treatment Approaches in Pancreatic Cancer)

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