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Cancers
Special Issues
Targeted Therapies in Pancreatic Cancer—Current Landscape and Future Directions
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Targeted Therapies in Pancreatic Cancer—Current Landscape and Future Directions

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

Deadline for manuscript submissions: 30 November 2025 | Viewed by 3444

Special Issue Editor

Dr. Yongwoo Dave Seo

E-Mail Website
Guest Editor
Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Interests: pancreatic neoplasms

Special Issue Information

Dear Colleagues,

Pancreatic cancer remains one of the most challenging malignancies to treat, with a notoriously low survival rate and often late-stage diagnosis. Recent advancements in targeted therapies offer new hope and opportunities for improved outcomes in this aggressive cancer. By honing in on specific molecular and genetic abnormalities, targeted therapies aim to disrupt cancer progression while minimizing the impact on healthy tissues. This Special Issue, titled "Targeted Therapies in Pancreatic Cancer—Current Landscape and Future Directions", seeks to explore the latest breakthroughs and ongoing research in this dynamic field. We will focus on novel therapeutic targets, including advancements in the inhibitors of KRAS and other oncogenic pathways; the role of immunotherapy; artificial intelligence and its ability to predict sensitivity to targeted agents; and personalized medicine approaches that promise to transform the landscape of pancreatic cancer treatment. Our aim is to bring together insights from leading researchers and clinicians to propel our understanding and treatment of pancreatic cancer in this rapidly evolving landscape of targeted therapies. We invite contributions that discuss innovative therapeutic strategies, novel translational research, breaking clinical trial results, and thoughtful perspectives on the future of pancreatic cancer care.

Dr. Yongwoo Dave Seo
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 100 words) can be sent to the Editorial Office for announcement on this website.

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
  • precision oncology
  • targeted therapies
  • immunotherapy
  • KRAS inhibitors
  • novel clinical trial design

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (2 papers)

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Review

21 pages, 1557 KB  
Review
Neoadjuvant Therapy or Upfront Surgery for Pancreatic Cancer—To Whom, When, and How?
by Daria Kwaśniewska, Marta Fudalej, Anna Maria Badowska-Kozakiewicz, Aleksandra Czerw and Andrzej Deptała
Cancers 2025, 17(15), 2584; https://doi.org/10.3390/cancers17152584 - 6 Aug 2025
Viewed by 1121
Abstract
The management of resectable pancreatic ductal adenocarcinoma (R-PDAC) and borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) remains a topic of active debate. Although neoadjuvant therapy (NAT) has shown clinical benefits in BR-PDAC, especially in increasing resectability and achieving higher rates of margin-negative (R0) resections, [...] Read more.
The management of resectable pancreatic ductal adenocarcinoma (R-PDAC) and borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) remains a topic of active debate. Although neoadjuvant therapy (NAT) has shown clinical benefits in BR-PDAC, especially in increasing resectability and achieving higher rates of margin-negative (R0) resections, its role in R-PDAC is less clearly defined. Additionally, the role of immunotherapy in PDAC is still being explored, with ongoing trials investigating new combinations to overcome the tumor’s immune-resistant microenvironment. This article provides a comprehensive narrative review of the current evidence comparing NAT with upfront surgery in pancreatic cancer management, focusing on randomized controlled trials and meta-analyses that assess outcomes in R-PDAC and BR-PDAC. The review aims to determine whether NAT offers a significant survival advantage over traditional post-operative strategies and to clarify which clinical scenarios may benefit most from NAT. The literature was identified through a systematic search of PubMed, Scopus, and Google Scholar databases up to March 2025. Article selection adhered to the PRISMA guidelines. Our review of existing evidence supports NAT as the standard of care for BR-PDAC. Meanwhile, management of R-PDAC should be tailored individually, guided by risk stratification that considers both clinical parameters and molecular features. Immunotherapy and targeted therapies are still in early research phases, and their further integration as NAT remains controversial. Full article
(This article belongs to the Special Issue Targeted Therapies in Pancreatic Cancer—Current Landscape and Future Directions)
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34 pages, 2332 KB  
Review
Treatment of KRAS-Mutated Pancreatic Cancer: New Hope for the Patients?
by Kamila Krupa, Marta Fudalej, Emilia Włoszek, Hanna Miski, Anna M. Badowska-Kozakiewicz, Dominika Mękal, Michał P. Budzik, Aleksandra Czerw and Andrzej Deptała
Cancers 2025, 17(15), 2453; https://doi.org/10.3390/cancers17152453 - 24 Jul 2025
Viewed by 1934
Abstract
Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), ranks among the most lethal malignancies, with a 5-year survival rate of under 10%. The most prevalent KRAS mutations occur in three hotspot residues: glycine-12 (G12), glycine-13 (G13), and glutamine-61 (Q61), leading to the constant activation [...] Read more.
Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), ranks among the most lethal malignancies, with a 5-year survival rate of under 10%. The most prevalent KRAS mutations occur in three hotspot residues: glycine-12 (G12), glycine-13 (G13), and glutamine-61 (Q61), leading to the constant activation of the Ras pathway, making them the primary focus in oncologic drug development. Selective KRAS G12C inhibitors (e.g., sotorasib, adagrasib) have demonstrated moderate efficacy in clinical trials; however, this mutation is infrequent in PDAC. Emerging therapies targeting KRAS G12D and G12V mutations, such as MRTX1133, PROTACs, and active-state inhibitors, show promise in preclinical studies. Pan-RAS inhibitors like ADT-007, RMC-9805, and RMC-6236 compounds provide broader coverage of mutations. Their efficacy and safety are currently being investigated in several clinical trials. A major challenge is the development of resistance mechanisms, including secondary mutations and pathway reactivation. Combination therapies targeting the RAS/MAPK axis, SHP2, mTOR, or SOS1 are under clinical investigation. Immunotherapy alone has demonstrated limited effectiveness, attributed to an immunosuppressive tumor microenvironment, although synergistic effects are noted when paired with KRAS-targeted agents. Furthermore, KRAS mutations reprogram cancer metabolism, enhancing glycolysis, macropinocytosis, and autophagy, which are being explored therapeutically. RNA interference technologies have also shown potential in silencing mutant KRAS and reducing tumorigenicity. Future strategies should emphasize the combination of targeted therapies with metabolic or immunomodulatory agents to overcome resistance and enhance survival in KRAS-mutated PDAC. Full article
(This article belongs to the Special Issue Targeted Therapies in Pancreatic Cancer—Current Landscape and Future Directions)
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