Tumor microenvironment in pancreatic ductal adenocarcinoma: Implications in immunotherapy

Smith, Caitlyn; Zheng, Wei; Dong, Jixin; Wang, Yaohong; Lai, Jinping; Liu, Xiuli; Yin, Feng

doi:10.3748/wjg.v28.i27.3297

Cited by 10 publications

(11 citation statements)

References 132 publications

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“…Investigations into the pancreatic tumor microenvironment will pave the way for a new treatment approach that combines immune checkpoint inhibitors and chemotherapy along with cancer vaccines to tackle PDAC. Overcoming current challenges in both preclinical and clinical studies will be crucial to demonstrating the effectiveness of utilizing immune checkpoint inhibitors in treating PDAC [ 11 , 171 ].…”

Section: Targeted Therapeutic Approachesmentioning

confidence: 99%

Clinical and Preclinical Targeting of Oncogenic Pathways in PDAC: Targeted Therapeutic Approaches for the Deadliest Cancer

Jiménez,

Javed,

Rubio-Tomás

et al. 2024

IJMS

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Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. It is commonly diagnosed in advanced stages and therapeutic interventions are typically constrained to systemic chemotherapy, which yields only modest clinical outcomes. In this review, we examine recent developments in targeted therapy tailored to address distinct molecular pathway alteration required for PDAC. Our review delineates the principal signaling pathways and molecular mechanisms implicated in the initiation and progression of PDAC. Subsequently, we provide an overview of prevailing guidelines, ongoing investigations, and prospective research trajectories related to targeted therapeutic interventions, drawing insights from randomized clinical trials and other pertinent studies. This review focus on a comprehensive examination of preclinical and clinical data substantiating the efficacy of these therapeutic modalities, emphasizing the potential of combinatorial regimens and novel therapies to enhance the quality of life for individuals afflicted with PDAC. Lastly, the review delves into the contemporary application and ongoing research endeavors concerning targeted therapy for PDAC. This synthesis serves to bridge the molecular elucidation of PDAC with its clinical implications, the evolution of innovative therapeutic strategies, and the changing landscape of treatment approaches.

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Section: Targeted Therapeutic Approachesmentioning

confidence: 99%

Clinical and Preclinical Targeting of Oncogenic Pathways in PDAC: Targeted Therapeutic Approaches for the Deadliest Cancer

Jiménez,

Javed,

Rubio-Tomás

et al. 2024

IJMS

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“…The baseline immune status predicts PDAC disease course and overall survival in NCT01280058 ( 255 ). Tremelimumab monotherapy is ineffective for metastatic PDAC (NCT02527434) ( 256 ). New therapeutic options are being studied in the clinical trials: NCT02981342, NCT02558894, NCT02178709.…”

Section: Recent Clinical Trialsmentioning

confidence: 99%

Innate and adaptive immune-directed tumour microenvironment in pancreatic ductal adenocarcinoma

Joseph,

Al Aiyan,

Al-Ramadi

et al. 2024

Front. Immunol.

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One of the most deadly and aggressive cancers in the world, pancreatic ductal adenocarcinoma (PDAC), typically manifests at an advanced stage. PDAC is becoming more common, and by the year 2030, it is expected to overtake lung cancer as the second greatest cause of cancer-related death. The poor prognosis can be attributed to a number of factors, including difficulties in early identification, a poor probability of curative radical resection, limited response to chemotherapy and radiotherapy, and its immunotherapy resistance. Furthermore, an extensive desmoplastic stroma that surrounds PDAC forms a mechanical barrier that prevents vascularization and promotes poor immune cell penetration. Phenotypic heterogeneity, drug resistance, and immunosuppressive tumor microenvironment are the main causes of PDAC aggressiveness. There is a complex and dynamic interaction between tumor cells in PDAC with stromal cells within the tumour immune microenvironment. The immune suppressive microenvironment that promotes PDAC aggressiveness is contributed by a range of cellular and humoral factors, which itself are modulated by the cancer. In this review, we describe the role of innate and adaptive immune cells, complex tumor microenvironment in PDAC, humoral factors, innate immune-mediated therapeutic advances, and recent clinical trials in PDAC.

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“…Cancer-associated fibroblasts (CAFs) are one of the important components of tumor stroma. CAFs produce chemokines, cytokines and TME proteins, all of which are required for tumor architecture, growth, invasion and metastasis [ 85 , 86 , 87 ]. CAFs’ morphology and gene expression profiles are similar to those of myofibroblasts [ 86 ].…”

Section: Tumor-derived Sevs Play Vital Roles In the Bc Microenvironmentmentioning

confidence: 99%

Tumor-Derived Small Extracellular Vesicles Involved in Breast Cancer Progression and Drug Resistance

Feng

Guo

Tanaka

et al. 2022

IJMS

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Breast cancer is one of the most serious and terrifying threats to the health of women. Recent studies have demonstrated that interaction among cancer cells themselves and those with other cells, including immune cells, in a tumor microenvironment potentially and intrinsically regulate and determine cancer progression and metastasis. Small extracellular vesicles (sEVs), a type of lipid-bilayer particles derived from cells, with a size of less than 200 nm, are recognized as one form of important mediators in cell-to-cell communication. sEVs can transport a variety of bioactive substances, including proteins, RNAs, and lipids. Accumulating evidence has revealed that sEVs play a crucial role in cancer development and progression, with a significant impact on proliferation, invasion, and metastasis. In addition, sEVs systematically coordinate physiological and pathological processes, such as coagulation, vascular leakage, and stromal cell reprogramming, to bring about premetastatic niche formation and to determine metastatic organ tropism. There are a variety of oncogenic factors in tumor-derived sEVs that mediate cellular communication between local stromal cells and distal microenvironment, both of which are important in cancer progression and metastasis. Tumor-derived sEVs contain substances that are similar to parental tumor cells, and as such, sEVs could be biomarkers in cancer progression and potential therapeutic targets, particularly for predicting and preventing future metastatic development. Here, we review the mechanisms underlying the regulation by tumor-derived sEVs on cancer development and progression, including proliferation, metastasis, drug resistance, and immunosuppression, which coordinately shape the pro-metastatic microenvironment. In addition, we describe the application of sEVs to the development of cancer biomarkers and potential therapeutic modalities and discuss how they can be engineered and translated into clinical practice.

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Tumor microenvironment in pancreatic ductal adenocarcinoma: Implications in immunotherapy

Cited by 10 publications

References 132 publications

Clinical and Preclinical Targeting of Oncogenic Pathways in PDAC: Targeted Therapeutic Approaches for the Deadliest Cancer

Clinical and Preclinical Targeting of Oncogenic Pathways in PDAC: Targeted Therapeutic Approaches for the Deadliest Cancer

Innate and adaptive immune-directed tumour microenvironment in pancreatic ductal adenocarcinoma

Tumor-Derived Small Extracellular Vesicles Involved in Breast Cancer Progression and Drug Resistance

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