Chemotherapy and tumor microenvironment of pancreatic cancer

Liu, Qiaofei; Liao, Quan; Zhao, Yupei

doi:10.1186/s12935-017-0437-3

Cited by 105 publications

(91 citation statements)

References 216 publications

(238 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These observations support targeting the TME through therapeutic intervention to decrease tumor-cell growth and motility (87,88). A dense TME has been shown in previous studies to limit therapeutic efficacy, and many dense tumors are resistant to chemotherapy (87)(88)(89)(90). It has been proposed that this is because of decreased delivery of drug to the tumor site due to transport barriers to drug delivery.…”

Section: Discussionmentioning

confidence: 59%

Crosshatch nanofiber networks of tunable interfiber spacing induce plasticity in cell migration and cytoskeletal response

Jana¹,

Nookaew

Singh³

et al. 2019

FASEB j.

View full text Add to dashboard Cite

Biomechanical cues within tissue microenvironments are critical for maintaining homeostasis, and their disruption can contribute to malignant transformation and metastasis. Once transformed, metastatic cancer cells can migrate persistently by adapting (plasticity) to changes in the local fibrous extracellular matrix, and current strategies to recapitulate persistent migration rely exclusively on the use of aligned geometries. Here, the controlled interfiber spacing in suspended Crosshatch networks of nanofibers induces cells to exhibit plasticity in migratory behavior (persistent and random) and the associated cytoskeletal arrangement. At dense spacing (3 and 6 µm), unexpectedly, elongated cells migrate persistently (in 1 dimension) at high speeds in 3‐dimensional shapes with thick nuclei, and short focal adhesion cluster (FAC) lengths. With increased spacing (18 and 36 µm), cells attain 2‐dimensional morphologies, have flattened nuclei and longer FACs, and migrate randomly by rapidly detaching their trailing edges that strain the nuclei by ∼35%. At 54‐µm spacing, kite‐shaped cells become near stationary. Poorly developed filamentous actin stress fibers are found only in cells on 3‐µm networks. Gene‐expression profiling shows a decrease in transcriptional potential and a differential up‐regulation of metabolic pathways. The consistency in observed phenotypes across cell lines supports using this platform to dissect hallmarks of plasticity in migration in vitro.—Jana, A., Nookaew, I., Singh, J., Behkam, B., Franco, A. T., Nain, A. S. Crosshatch nanofiber networks of tunable interfiber spacing induce plasticity in cell migration and cytoskeletal response. FA8EB J. 33, 10618–10632 (2019). http://www.fasebj.org

show abstract

Section: Discussionmentioning

confidence: 59%

Crosshatch nanofiber networks of tunable interfiber spacing induce plasticity in cell migration and cytoskeletal response

Jana¹,

Nookaew

Singh³

et al. 2019

FASEB j.

View full text Add to dashboard Cite

show abstract

“…In some cases, chemo-and radiotherapies could foster anti-tumor activity by changing the TME. Gemcitabine and 5-fluorouracil (5FU) treatments were selectively cytotoxic on MDSCs and the elimination of MDSCs increased the activity of CD8 + cells [6]. Treatment of eribulin mesylate, which is a tubulin binding drug, inhibits tumor progression by increasing the vessels density and NK cell infiltration in TME [8].…”

Section: Chemo-and Radiotherapiesmentioning

confidence: 99%

“…Given the profound crosstalk that exists between malignant cells and TME, therapies that aim to eliminate cancer cells often stimulate the remodeling of TME. Studies suggest that chemo-and radiotherapies could modulate TME to be more immunogenic and result in a synergistic tumor killing effect [6][7][8]. In contrast, during treatments, TME could protect tumor cells by creating "barriers" to prevent drug penetration or immune effector cell infiltration [9,10].…”

Section: Introductionmentioning

confidence: 99%

Complex interplay between tumor microenvironment and cancer therapy

Shen

Kang

2018

Front. Med.

View full text Add to dashboard Cite

Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist within and around the tumor mass. The TME is highly dynamic and its importance in different stages of cancer progression has been well recognized. A growing body of evidence suggests that TME also plays pivotal roles in cancer treatment responses. TME is significantly remodeled upon cancer therapies, and such change either enhances the responses or induces drug resistance. Given the importance of TME in tumor progression and therapy resistance, strategies that remodel TME to improve therapeutic responses are under developing. In this review, we provide an overview of the essential components in TME and the remodeling of TME in response to anti-cancer treatments. We also summarize the strategies that aim to enhance therapeutic efficacy by modulating TME.

show abstract

“…PaCa microenvironment is composed of a highly heterogeneous collection of cancer cells, extracellular matrix and various stromal, endothelial cells, inflammatory cells, immune cells (T cells, tumor-associated macrophages) and cancer stem cells that have tumor-promoting functions (25,26). Extreme desmoplastic reaction and excess stroma formation is an important charasteristic of PDAC, promoting tumor growth, progression and drug resistance (27). There is a dynamic bi-directional crosstalk between stromal and cancer cells, leading to activation of oncogenic signaling pathways and immune suppression.…”

Section: Etiology Genetics and Biology Of Pancreatic Ductal Adenocarmentioning

confidence: 99%

Targeted Therapies for Pancreatic Cancer and Hurdles Ahead

et al. 2018

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers with a median survival of 6 months after diagnosis. Intrinsic resistance to chemotherapeutics and lack of effective targeted therapies are the major factors contributing to dismal prognosis. Several important genetic alterations (i.e., mutations, deletions) have been identified to be involved in the initiation and progression of pancreatic cancer, including KRAS and inactivation of tumor suppressors, such as TP53, SMAD4 and CDKN2A. Unique tumor microenvironment with excessive stroma due to desmoplastic reaction is one of the major characteristics of PDAC, promoting tumor growth and leading to treatment failures. In addition, tumor stroma represents an important biological barrier for drug delivery and successful treatment of PDAC. Small interfering RNA (siRNA) has recently emerged as a potential and targeted therapeutic approach which is now evaluated in clinical trials. However, siRNAbased therapeutics face important challenges, including rapid serum degradation, poor tumor cell uptake and cellular uptake, leading to off-target effects. Therefore, there is a great need for the development of safe and effective nanoparticles for better tumor-specific delivery of anti-cancer therapeutics. In this article, the main challenges in the treatment of pancreatic cancer and recent advancements on nano delivery systems of chemotherapeutics and gene-targeted agents, used both in preclinical and clinical trials are reviewed.

show abstract

Chemotherapy and tumor microenvironment of pancreatic cancer

Cited by 105 publications

References 216 publications

Crosshatch nanofiber networks of tunable interfiber spacing induce plasticity in cell migration and cytoskeletal response

Crosshatch nanofiber networks of tunable interfiber spacing induce plasticity in cell migration and cytoskeletal response

Complex interplay between tumor microenvironment and cancer therapy

Targeted Therapies for Pancreatic Cancer and Hurdles Ahead

Contact Info

Product

Resources

About