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Review
. 2025 Mar 18:6:1002299.
doi: 10.37349/etat.2025.1002299. eCollection 2025.

Pancreatic cancer: failures and hopes-a review of new promising treatment approaches

Affiliations
Review

Pancreatic cancer: failures and hopes-a review of new promising treatment approaches

Vittore Cereda et al. Explor Target Antitumor Ther. .

Abstract

Pancreatic cancer is a challenging disease with limited treatment options and a high mortality rate. Just few therapy advances have been made in recent years. Tumor microenvironment, immunosuppressive features and mutational status represent important obstacles in the improvement of survival outcomes. Up to now, first-line therapy did achieve a median overall survival of less than 12 months and this discouraging data lead clinicians all over the world to focus their efforts on various fields of investigation: 1) sequential cycling of different systemic therapy in order to overcome mechanisms of resistance; 2) discovery of new predictive bio-markers, in order to target specific patient population; 3) combination treatment, in order to modulate the tumor microenvironment of pancreatic cancer; 4) new modalities of the delivery of drugs in order to pass the physical barrier of desmoplasia and tumor stroma. This review shows future directions of treatment strategies in advanced pancreatic cancer through a deep analysis of these recent macro areas of research.

Keywords: KRAS; Pancreatic cancer; immunotherapy; tumor microenvironment.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Tumor microenvironment (TME) in pancreatic cancer and resistance to systemic therapy. The figure shows the interplay between TME, tumor cells and immunogenic cells, which induces the increase of metastatic potential and immunosuppressive behavior of pancreatic cancer. Pancreatic cancer cells (PCA cells) with KRAS mutations lead the establishment of immunosuppression within the TME, modulating MHC class I levels and expression of CD47 and PD-L1; promoting myeloid-derived suppressor cells (MDSCs) infiltration, through the production of GM-CSF and CXCL1; increasing the levels of COX2, IL-6 and MMP7 with the expansion of fibro-inflammatory stroma (desmoplastic reaction). Carcinoma-associated fibroblasts (CAFs), derived from the activation of pancreatic stellate cells (PSCs), produce a variety of extracellular matrix proteins, forming a “barrier” against the release of chemotherapeutic agents and immunotherapies, and increase the levels of cytokines, inducing the migration of altered vascular endothelial cells and immunogenic cells with immunosuppressive properties. Infiltrated immunogenic cells are MDSCs; tumor-associated macrophages (TAMs) and Tregs, that are able to inhibit T-lymphocyte responses; tumor-infiltrating lymphocytes (TILs), that are presented in a smaller numbers and trapped within the TME. In this context the role of collapsed blood vessels should not be underestimated, because they increase hypoxia and the levels of free radicals, promoting cancer cells development and aggressiveness and helping to induce an immunosuppressive environment

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References

    1. Cancer Stat Facts: Pancreatic Cancer [Internet] [Cited 2023 Mar 12]. Available from: https://seer.cancer.gov/statfacts/html/pancreas.html .
    1. Survival Rates for Pancreatic Cancer [Internet] American Cancer Society, Inc; c2025 [cited 2023 Mar 12]. Available from: https://www.cancer.org/cancer/types/pancreatic-cancer/detection-diagnosi... .
    1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74:12–49. doi: 10.3322/caac.21820. - DOI - PubMed
    1. Hernández-Blanquisett A, Quintero-Carreño V, Martínez-Ávila MC, Porto M, Manzur-Barbur MC, Buendía E. Metastatic Pancreatic Cancer: Where Are We? Oncol Rev. 2024;17:11364. doi: 10.3389/or.2023.11364. - DOI - PMC - PubMed
    1. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13. doi: 10.1200/JCO.1997.15.6.2403. - DOI - PubMed

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