Stroma-Targeting Therapy in Pancreatic Cancer: One Coin With Two Sides?

Jiang, Bolun; Zhou, Li; Lü, Jun; Wang, Yizhi; Liu, Chengxi; You, Lei; Guo, Junchao

doi:10.3389/fonc.2020.576399

Cited by 65 publications

(54 citation statements)

References 99 publications

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“…Thus, Sonic HedgeHog (SHH), Fibroblast Growth Factor-2 (FGF-2) and Platelet-derived Growth Factor (PDGF) are overexpressed during PDAC and interfering with their signaling corresponds to valuable strategies for PDAC treatment (40,82). However, clinical trials using IPI-926, vismodegib and sonidegib that target the hedgehog pathway have so far been disappointing (123). PDAC cells also overexpress several CXC ligands, which are involved in desmoplastic reaction, immune modulation and tumor angiogenesis (36,124).…”

Section: Matrisome-associated Proteins Secreted Factorsmentioning

confidence: 99%

Stroma Involvement in Pancreatic Ductal Adenocarcinoma: An Overview Focusing on Extracellular Matrix Proteins

et al. 2021

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Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide and is predicted to become second in 2030 in industrialized countries if no therapeutic progress is made. Among the different types of pancreatic cancers, Pancreatic Ductal Adenocarcinoma (PDAC) is by far the most represented one with an occurrence of more than 90%. This specific cancer is a devastating malignancy with an extremely poor prognosis, as shown by the 5-years survival rate of 2–9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Pancreatic tumors progress with few specific symptoms and are thus at an advanced stage at diagnosis in most patients. This malignancy is characterized by an extremely dense stroma deposition around lesions, accompanied by tissue hypovascularization and a profound immune suppression. Altogether, these combined features make access to cancer cells almost impossible for conventional chemotherapeutics and new immunotherapeutic agents, thus contributing to the fatal outcomes of the disease. Initially ignored, the Tumor MicroEnvironment (TME) is now the subject of intensive research related to PDAC treatment and could contain new therapeutic targets. In this review, we will summarize the current state of knowledge in the field by focusing on TME composition to understand how this specific compartment could influence tumor progression and resistance to therapies. Attention will be paid to Tenascin-C, a matrix glycoprotein commonly upregulated during cancer that participates to PDAC progression and thus contributes to poor prognosis.

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Section: Matrisome-associated Proteins Secreted Factorsmentioning

confidence: 99%

Stroma Involvement in Pancreatic Ductal Adenocarcinoma: An Overview Focusing on Extracellular Matrix Proteins

et al. 2021

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“…However, PDAC in Sonic Hedgehog knockout mice show earlier metastasis and thus poorer prognosis [ 16 , 27 ]. Furthermore, several clinical trials targeting stroma in PDAC have shown limited efficacy [ 28 ]. These—in part contradictory—findings indicate the need for further research in this area.…”

Section: Discussionmentioning

confidence: 99%

“…Further prospective studies validating such an approach are required. The impact of tumor cellularity on the response to chemotherapeutic drugs is still subject to research, as promising results of pre-clinical studies investigating stroma-targeted therapy were not fully reproducible in humans so far [ 28 ]. However, in the course of development of personalized medicine techniques, non-invasive prediction of tumor cell content and thus better tumor characterization may contribute to improved individual therapy for PDAC patients.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Tumor Cellularity in Resectable PDAC from Preoperative Computed Tomography Imaging

Jungmann

Kaissis

Ziegelmayer

et al. 2021

Cancers

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Background: PDAC remains a tumor entity with poor prognosis and a 5-year survival rate below 10%. Recent research has revealed invasive biomarkers, such as distinct molecular subtypes, predictive for therapy response and patient survival. Non-invasive prediction of individual patient outcome however remains an unresolved task. Methods: Discrete cellularity regions of PDAC resection specimen (n = 43) were analyzed by routine histopathological work up. Regional tumor cellularity and CT-derived Hounsfield Units (HU, n = 66) as well as iodine concentrations were regionally matched. One-way ANOVA and pairwise t-tests were performed to assess the relationship between different cellularity level in conventional, virtual monoenergetic 40 keV (monoE 40 keV) and iodine map reconstructions. Results: A statistically significant negative correlation between regional tumor cellularity in histopathology and CT-derived HU from corresponding image regions was identified. Radiological differentiation was best possible in monoE 40 keV CT images. However, HU values differed significantly in conventional reconstructions as well, indicating the possibility of a broad clinical application of this finding. Conclusion: In this study we establish a novel method for CT-based prediction of tumor cellularity for in-vivo tumor characterization in PDAC patients.

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“…Pancreatic ductal adenocarcinoma (PDAC) is known for its abundant immunosuppressive stroma, reaching up to 70% of the tumor volume [ 108 ]. Hence, most in vivo studies of adoptive cell therapies reported unsatisfactory outcomes, with the stroma responsible for suppressing ACTs’ anti-PDAC potential.…”

Section: Preclinical Data On Car-nk Cells In Solid Tumorsmentioning

confidence: 99%

CAR-NK Cells in the Treatment of Solid Tumors

Wrona

Borowiec

Potemski

2021

IJMS

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CAR-T (chimeric antigen receptor T) cells have emerged as a milestone in the treatment of patients with refractory B-cell neoplasms. However, despite having unprecedented efficacy against hematological malignancies, the treatment is far from flawless. Its greatest drawbacks arise from a challenging and expensive production process, strict patient eligibility criteria and serious toxicity profile. One possible solution, supported by robust research, is the replacement of T lymphocytes with NK cells for CAR expression. NK cells seem to be an attractive vehicle for CAR expression as they can be derived from multiple sources and safely infused regardless of donor–patient matching, which greatly reduces the cost of the treatment. CAR-NK cells are known to be effective against hematological malignancies, and a growing number of preclinical findings indicate that they have activity against non-hematological neoplasms. Here, we present a thorough overview of the current state of knowledge regarding the use of CAR-NK cells in treating various solid tumors.

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Stroma-Targeting Therapy in Pancreatic Cancer: One Coin With Two Sides?

Cited by 65 publications

References 99 publications

Stroma Involvement in Pancreatic Ductal Adenocarcinoma: An Overview Focusing on Extracellular Matrix Proteins

Stroma Involvement in Pancreatic Ductal Adenocarcinoma: An Overview Focusing on Extracellular Matrix Proteins

Prediction of Tumor Cellularity in Resectable PDAC from Preoperative Computed Tomography Imaging

CAR-NK Cells in the Treatment of Solid Tumors

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