Complex interplay between tumor microenvironment and cancer therapy

Shen, Minhong; Kang, Yibin

doi:10.1007/s11684-018-0663-7

Cited by 44 publications

(41 citation statements)

References 149 publications

(132 reference statements)

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“…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: 60%

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

Jana¹,

Nookaew

Singh³

et al. 2019

FASEB j.

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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

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Section: Discussionmentioning

confidence: 60%

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

Jana¹,

Nookaew

Singh³

et al. 2019

FASEB j.

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“…CRCs require interaction with many different host immune cell populations for their growth and survival, including regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC), mast cells, and tumor associated macrophages (TAM) [55]. Recent studies suggest that a substantial portion of the effects attributed to EGFR antagonist treatment may be based on indirect effects beyond cancer cells [40,41,42,55,56,57,58,59,60,61,62].…”

Section: Contribution Of Tumor Microenvironment To Acquired Resistmentioning

confidence: 99%

Immune Resistance and EGFR Antagonists in Colorectal Cancer

Giordano

Remo²,

Porrás

et al. 2019

Cancers

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: Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy in patients with RAS wild type metastatic colorectal cancer (mCRC) has revolutionized the treatment of CRC, but with less results than initially envisaged. In recent years, the discovery of multiple pathways leading to the escape from anti-EGFR therapy has revealed an enormous complexity and heterogeneity of human CRC due to the intrinsic genomic instability and immune/cancer cell interaction. Therefore, understanding the mechanistic basis of acquired resistance to targeted therapies represents a major challenge to improve the clinical outcomes of patients with CRC. The latest findings strongly suggest that complex molecular alterations coupled with changes of the immune tumor microenvironment may substantially contribute to the clinical efficacy of EGFR antagonist. In this review, we discuss the most recent findings that contribute to both primary and acquired anti-EGFR therapy resistance. In addition, we analyze how strategies aiming to enhance the favorable effects in the tumor microenvironment may contribute to overcome resistance to EGFR therapies.

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“…Another reason to pay attention to Notch-Wnt interactions is that both pathways are activated by tumor therapy, and this activation contributes to therapy resistance. Thus, both chemo- and radiotherapy lead to enhanced production of Notch and Wnt ligands in the tumor stroma (for review see [112]). Paclitaxel and cisplatin remodel the tumor microenvironment leading to enhanced Jagged1 expression in the tumor stroma, which may elicit increased Notch activation in the tumor proper [113].…”

Section: Notch and Wnt Signaling In Breast Cancermentioning

confidence: 99%

Notch and Wnt Dysregulation and Its Relevance for Breast Cancer and Tumor Initiation

2018

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Breast cancer is the second leading cause of cancer deaths among women in the world. Treatment has been improved and, in combination with early detection, this has resulted in reduced mortality rates. Further improvement in therapy development is however warranted. This will be particularly important for certain sub-classes of breast cancer, such as triple-negative breast cancer, where currently no specific therapies are available. An important therapy development focus emerges from the notion that dysregulation of two major signaling pathways, Notch and Wnt signaling, are major drivers for breast cancer development. In this review, we discuss recent insights into the Notch and Wnt signaling pathways and into how they act synergistically both in normal development and cancer. We also discuss how dysregulation of the two pathways contributes to breast cancer and strategies to develop novel breast cancer therapies starting from a Notch and Wnt dysregulation perspective.

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Complex interplay between tumor microenvironment and cancer therapy

Cited by 44 publications

References 149 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

Immune Resistance and EGFR Antagonists in Colorectal Cancer

Notch and Wnt Dysregulation and Its Relevance for Breast Cancer and Tumor Initiation

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