Dataset Information

Nanoparticle-Based Therapeutic Strategies for Enhanced Pancreatic Ductal Adenocarcinoma Immunotherapy.

ABSTRACT: Immunotherapy has dramatically changed prognosis for patients with malignant tumors. However, as a non-immunogenic tumor, pancreatic ductal adenocarcinoma (PDAC) has a low response to immunotherapy. Factors that contribute to the inefficiency of PDAC immunotherapy include the tumor microenvironment (TME) and its dense stroma, which acts as a barrier for drug delivery and immune cell infiltration. Recent studies have shown that nanoparticle-based therapeutic strategies have more promising applications in improving drug delivery and reversing the immunosuppressive TME for PDAC. Therefore, nanomaterial-based therapeutic approaches are expected to enhance the effectiveness of immunotherapy and improve prognosis of patients with PDAC. Here, we outline the status and dilemma of PDAC immunotherapy, and summarize the latest advances in nanoparticle-based treatment strategies to enhance the efficacy of PDAC immunotherapy.

SUBMITTER: Hou W

PROVIDER: S-EPMC9607590 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Nanoparticle-Based Therapeutic Strategies for Enhanced Pancreatic Ductal Adenocarcinoma Immunotherapy.

Hou Wanting W Yang Biao B Zhu Hong H

Pharmaceutics 20220924 10

Immunotherapy has dramatically changed prognosis for patients with malignant tumors. However, as a non-immunogenic tumor, pancreatic ductal adenocarcinoma (PDAC) has a low response to immunotherapy. Factors that contribute to the inefficiency of PDAC immunotherapy include the tumor microenvironment (TME) and its dense stroma, which acts as a barrier for drug delivery and immune cell infiltration. Recent studies have shown that nanoparticle-based therapeutic strategies have more promising applica ...[more]

PMID: 36297467

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced stage, with systemic therapy being the mainstay of treatment. Survival continues to be limited, typically less than 1 year. The PDAC microenvironment is characterized by a paucity of malignant epithelial cells, abundant stroma with predominantly immunosuppressive T cells and myelosuppressive-type macrophages (M2), and hypovascularity. The current treatment options for metastatic PDAC are modified (m)FOLFIRINOX /FOLFIRINOX or nab-paclitaxel and gemcitabine in patients with good performance status (PS) (ECOG 0-1/KPS 70-100%) and gemcitabine with or without a second agent for those with ECOG PS 2-3. New therapies are emerging, and the current guidelines endorse both germline and somatic testing in PDAC to evaluate actionable findings. Important themes related to new therapeutic approaches include DNA damage repair strategies, immunotherapy, targeting the stroma, and cancer-cell metabolism. Targeted therapy alone (outside small genomically defined subsets) or in combination with standard cytotoxic therapy, thus far, has proven disappointing in PDAC; however, novel therapies are evolving with increased integration of genomic profiling along with a better understanding of the tumor microenvironment and immunology. A small but important sub-group of patients have some of these agents available in the clinics for use. Olaparib was recently approved by the US Food and Drug Administration for maintenance therapy in germline BRCA1/2 mutated PDAC following demonstration of survival benefit in a phase 3 trial. Pembrolizumab is approved for patients with defects in mismatch repair/microsatellite instability. PDAC with wild-type KRAS represents a unique subgroup who have enrichment of potentially targetable oncogenic drivers. Small-molecule inhibitors including ERBB inhibitors (e.g., afatinib, MCLA-128), TRK inhibitors (e.g., larotrectinib, entrectinib), ALK/ROS inhibitor (e.g., crizotinib), and BRAF/MEK inhibitors are in development. In a small subset of patients with the KRASG12C mutation, a KRASG12C inhibitor, AMG510, and other agents are being investigated. Major efforts are underway to effectively target the tumor microenvironment and to integrate immunotherapy into the treatment of PDAC, and although thus far the impact has been modest to ineffective, nonetheless, there is optimism that some of the challenges will be overcome.

Dataset Information

Nanoparticle-Based Therapeutic Strategies for Enhanced Pancreatic Ductal Adenocarcinoma Immunotherapy.

Publications

Nanoparticle-Based Therapeutic Strategies for Enhanced Pancreatic Ductal Adenocarcinoma Immunotherapy.

Similar Datasets

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