Targeting Tumor-Associated Fibroblasts for Therapeutic Delivery in Desmoplastic Tumors

Miao, Lei; Liu, Qi; Lin, Chii M.; Luo, Cong; Wang, Yuhua; Liu, Lina; Yin, Weiyan; Hu, Shihao; Kim, William Y.; Huang, Leaf

doi:10.1158/0008-5472.can-16-0866

Cited by 182 publications

(157 citation statements)

References 48 publications

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“…Several recent studies have aimed to design NPs to target CAFs [144][145][146]. Wnt16 secreted by CAFs has been reported to be critical for the treatment resistance [144].…”

Section: Nanoparticle-based Strategiesmentioning

confidence: 99%

Complex interplay between tumor microenvironment and cancer therapy

Shen

Kang

2018

Front. Med.

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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.

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“…Several recent studies have aimed to design NPs to target CAFs [144][145][146]. Wnt16 secreted by CAFs has been reported to be critical for the treatment resistance [144].…”

Section: Nanoparticle-based Strategiesmentioning

confidence: 99%

Complex interplay between tumor microenvironment and cancer therapy

Shen

Kang

2018

Front. Med.

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“…We have also combined the method of reprogramming TAFs with the engineering of TAFs. Recently, the binding site barrier effect of fibroblasts was used to deliver plasmids encoding secretable TNF-related apoptosis-inducing ligand (TRAIL) to fibroblasts [216]. The anisamide targeted NP showed enhanced accumulation in fibroblasts due to overexpression of the sigma receptor.…”

Section: Tumor Microenvironment and Sequential/cascade Or Separatementioning

confidence: 99%

Nanoformulations for combination or cascade anticancer therapy

Miao

Guo

Lin

et al. 2017

Advanced Drug Delivery Reviews

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152

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Nanoparticle drug formulations have been extensively investigated, developed, and in some cases, approved by the Food and Drug Administration (FDA). Synergistic combinations of drugs having distinct tumor-inhibiting mechanisms and non-overlapping toxicity can circumvent the issue of treatment resistance and may be essential for effective anti-cancer therapy. At the same time, co-delivery of a combined regimen by a single nanocarrier presents a challenge due to differences in solubility, molecular weight, functional groups and encapsulation conditions between the two drugs. This review discusses cellular and microenvironment mechanisms behind treatment resistance and nanotechnology-based solutions for effective anti-cancer therapy. Co-loading or cascade delivery of multiple drugs using of polymeric nanoparticles, polymer-drug conjugates and lipid nanoparticles will be discussed along with lipid-coated drug nanoparticles developed by our lab and perspectives on combination therapy.

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“…As a result, the protein is more deeply diffused within hypovascular pancreatic cancers. 22–26 The advantages of NP-mediated, in situ expression of small proteins stretch far beyond simply enhancing transport in the tumor interstitium. PEGylated steric NP delivery vectors can also decrease systemic toxicity and improve the pharmacokinetic profiles of the encapsulated therapeutic agents.…”

mentioning

confidence: 99%

Transient and Local Expression of Chemokine and Immune Checkpoint Traps To Treat Pancreatic Cancer

et al. 2017

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Pancreatic tumors are known to be resistant to immunotherapy due to the extensive immune suppressive tumor microenvironment (TME). We hypothesized that CXCL12 and PD-L1 are two key molecules controlling the immunosuppressive TME. Fusion proteins, called traps, designed to bind with these two molecules with high affinity (Kd = 4.1 and 0.22 nM, respectively) were manufactured and tested for specific binding with the targets. Plasmid DNA encoding for each trap was formulated in nanoparticles and intravenously injected to mice bearing orthotopic pancreatic cancer. Expression of traps was mainly seen in the tumor, and secondarily, accumulations were primarily in the liver. Combination trap therapy shrunk the tumor and significantly prolonged the host survival. Either trap alone only brought in a partial therapeutic effect. We also found that CXCL12 trap allowed T-cell penetration into the tumor, and PD-L1 trap allowed the infiltrated T-cells to kill the tumor cells. Combo trap therapy also significantly reduced metastasis of the tumor cells to other organs. We conclude that the trap therapy significantly modified the immunosuppressive TME to allow the host immune system to kill the tumor cells. This can be an effective therapy in clinical settings.

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Targeting Tumor-Associated Fibroblasts for Therapeutic Delivery in Desmoplastic Tumors

Cited by 182 publications

References 48 publications

Complex interplay between tumor microenvironment and cancer therapy

Complex interplay between tumor microenvironment and cancer therapy

Nanoformulations for combination or cascade anticancer therapy

Transient and Local Expression of Chemokine and Immune Checkpoint Traps To Treat Pancreatic Cancer

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