Metastasis in Pancreatic Ductal Adenocarcinoma: Current Standing and Methodologies

Pereira, Marina Ayres; Chio, Iok In Christine

doi:10.3390/genes11010006

Cited by 44 publications

(44 citation statements)

References 180 publications

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“…There are preferential sites for metastases from PDAC, such as liver, lungs, and peritoneum (61). Interestingly, in the last years several works have suggested the possibility that organs-in particular the liver-could be induced in accepting tumor cells through secreted factors released by primary tumor, such as inhibitor of metalloproteinases or exosomes (so called "premetastastic niches") (62,63).…”

Section: Pdac Evolution: From Pancreatic Gland To Metastasismentioning

confidence: 99%

Adjuvant Treatment in Pancreatic Cancer: Shaping the Future of the Curative Setting

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease even in the early stages, despite progresses in surgical and pharmacological treatment in recent years. High potential for metastases is the main cause of therapeutic failure in localized disease, highlighting the current limited knowledge of underlying pathological processes. However, nowadays research is focusing on the search for personalized approaches also in the adjuvant setting for PDAC, by implementing the use of biomarkers and investigating new therapeutic targets. In this context, the aim of this narrative review is to summarize the current treatment scenario and new potential therapeutic approaches in early stage PDAC, from both a preclinical and clinical point of view. Additionally, the review examines the role of target therapies in localized PDAC and the influence of neoadjuvant treatments on survival outcomes.

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Section: Pdac Evolution: From Pancreatic Gland To Metastasismentioning

confidence: 99%

Adjuvant Treatment in Pancreatic Cancer: Shaping the Future of the Curative Setting

et al. 2021

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“…It has been reported that ~50% of patients have been confirmed to possess metastasized cancer cells (3). Despite continuous improvements in diagnosis and treatment, this type of cancer is almost invariably fatal, and the 5-year survival rate of patients is ~8% (4,5). PDAC has a high degree of malignant biological characteristics, including invasion and metastasis, which leads to a poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Huang

2020

Mol Med Rep

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The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is primarily due to the invasive and metastatic behaviors of this disease. Laminin-332 (LM-332) is a key component of the basement membrane barrier, and is associated with tumor metastasis. The present study provides evidence towards the potential function of LM-332 in carcinoma, indicating the distinct roles of the three LM-332 subunits (α3, β3 and γ2) in cell proliferation, migration, invasion, apoptosis and the epithelial-to-mesenchymal transition (EMT) in cancer. The roles of the α3, β3 and γ2 subunits in the malignant biological behavior of PDAC were investigated in the present study. It was revealed that the α3, β3 and γ2 subunits were upregulated in PDAC. Inhibition of all LM-332 subunits abrogated the tumorigenic outcomes, which included cell proliferation, apoptosis, invasion, migration and EMT in vitro. However, the three LM-332 subunits had different degrees of effects on biological behavior. It was observed that LAMA3 (α3) had a stronger effect on cell proliferation, migration and invasion. In addition, LAMB3 (β3) knockdown significantly increased E-cadherin levels and decreased vimentin levels, indicating that LAMB3 was associated with EMT. Likewise, LAMC2 (γ2) mediated proliferation, apoptosis, invasion and migration. However, small interfering (si)-LAMC2 promoted the progression of EMT, which was the opposite effect to that of si-LAMB3. The LM-332 subunits (α3, β3 and γ2) may be novel therapeutic targets of PDAC in the future.

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“…Our ability to mimic such dynamic cues (i.e., mechanical forces, hypoxia, and matrix stiffness) on a chip is crucial in modeling cellular events in cancer. For example, epithelial to mesenchymal transition (EMT), a key event in cancer progression and invasion, responds to such dynamic forces in the tumor [28][29][30][31]. The phenotypic transition of the cancerous epithelium into mesenchymal faith enhances their pro-survival tone, migratory capacity, and metastasis [30,32].…”

Section: Organ-on-a-chip (Ooc) Technology In Cancermentioning

confidence: 99%

Organ-Chip Models: Opportunities for Precision Medicine in Pancreatic Cancer

Haque

Rempert

Al-Hilal

et al. 2021

Cancers

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Pancreatic Ductal Adenocarcinoma (PDAC) is an expeditiously fatal malignancy with a five-year survival rate of 6–8%. Conventional chemotherapeutics fail in many cases due to inadequate primary response and rapidly developing resistance. This treatment failure is particularly challenging in pancreatic cancer because of the high molecular heterogeneity across tumors. Additionally, a rich fibro-inflammatory component within the tumor microenvironment (TME) limits the delivery and effectiveness of anticancer drugs, further contributing to the lack of response or developing resistance to conventional approaches in this cancer. As a result, there is an urgent need to model pancreatic cancer ex vivo to discover effective drug regimens, including those targeting the components of the TME on an individualized basis. Patient-derived three-dimensional (3D) organoid technology has provided a unique opportunity to study patient-specific cancerous epithelium. Patient-derived organoids cultured with the TME components can more accurately reflect the in vivo tumor environment. Here we present the advances in organoid technology and multicellular platforms that could allow for the development of “organ-on-a-chip” approaches to recapitulate the complex cellular interactions in PDAC tumors. We highlight the current advances of the organ-on-a-chip-based cancer models and discuss their potential for the preclinical selection of individualized treatment in PDAC.

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Metastasis in Pancreatic Ductal Adenocarcinoma: Current Standing and Methodologies

Cited by 44 publications

References 180 publications

Adjuvant Treatment in Pancreatic Cancer: Shaping the Future of the Curative Setting

Adjuvant Treatment in Pancreatic Cancer: Shaping the Future of the Curative Setting

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Organ-Chip Models: Opportunities for Precision Medicine in Pancreatic Cancer

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