Precision health for breast cancer metastasis: biomaterial scaffolds as an engineered metastatic niche to define, study, and monitor metastatic progression

Bushnell, Grace G.; Wicha, Max S.; Jeruss, Jacqueline S.; Shea, Lonnie D.

doi:10.18632/oncoscience.493

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…This site would then be sampled and the tissue molecularly profiled and results stratified akin to OncotypeDX or MammaPrint, which could then inform clinician decisions regarding treatments at early time points in the metastatic setting. Molecular staging may impact the understanding of disease subtypes and serve as a powerful tool for precision medicine that can be harnessed prior to substantial distant disease burden (91).…”

Section: Immune Cell Detection and Analysismentioning

confidence: 99%

Engineered Niches to Analyze Mechanisms of Metastasis and Guide Precision Medicine

et al. 2020

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◥Cancer metastasis poses a challenging problem both clinically and scientifically, as the stochastic nature of metastatic lesion formation introduces complexity for both early detection and the study of metastasis in preclinical models. Engineered metastatic niches represent an emerging approach to address this stochasticity by creating bioengineered sites where cancer can preferentially metastasize. As the engineered niche captures the earliest metastatic cells at a nonvital location, both noninvasive and biopsy-based monitoring of these sites can be performed routinely to detect metastasis early and monitor alterations in the forming metastatic niche. The engineered metastatic niche also provides a new platform technology that serves as a tunable site to molecularly dissect metastatic disease mechanisms. Ultimately, linking the engineered niches with advances in sensor development and synthetic biology can provide enabling tools for preclinical cancer models and fosters the potential to impact the future of clinical cancer care.

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Section: Immune Cell Detection and Analysismentioning

confidence: 99%

Engineered Niches to Analyze Mechanisms of Metastasis and Guide Precision Medicine

et al. 2020

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“…Crucially, the 3D scaffold facilitates the implantation of these dormant microenvironments into the subcutaneous space of mice, resulting in development of an inhibitory (i.e., dormant) or a supportive niche in vivo. The second of these models was developed by the Shea lab and utilized a microporous polymer scaffold and implantation into tumor-bearing mice to generate a niche in vivo to which metastatic tumor cells home 113 – 115 . This approach facilitates the development and study of the metastatic niche in vivo and can be expanded via explantation of the engineered niche and subsequent culture in vitro 116 , 117 .…”

Section: The Clinical Problem Of Breast Cancer Dormancymentioning

confidence: 99%

Breast cancer dormancy: need for clinically relevant models to address current gaps in knowledge

et al. 2021

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Breast cancer is the most commonly diagnosed cancer in the USA. Although advances in treatment over the past several decades have significantly improved the outlook for this disease, most women who are diagnosed with estrogen receptor positive disease remain at risk of metastatic relapse for the remainder of their life. The cellular source of late relapse in these patients is thought to be disseminated tumor cells that reactivate after a long period of dormancy. The biology of these dormant cells and their natural history over a patient’s lifetime is largely unclear. We posit that research on tumor dormancy has been significantly limited by the lack of clinically relevant models. This review will discuss existing dormancy models, gaps in biological understanding, and propose criteria for future models to enhance their clinical relevance.

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Inflammation drives tumor growth in an immunocompetent implantable metastasis model

Giles,

Lee

2024

Preprint

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Nearly 90% of cancer deaths are due to metastasis. Conventional cancer therapeutics including chemotherapy, surgery, and radiotherapy, are effective in treating primary tumors, but may aggravate disseminated tumor cells (DTCs) into regaining a proliferative state. Models isolating the post dissemination environment are needed to address the potential risks of these therapies, however modeling post dissemination environments is challenging. Often, host organisms become moribund due to primary tumor mass before native metastatic niches can evolve. Implantable tissue engineered niches have been used to attract circulating tumor cells independent of the primary tumor. Here, we serially transplant such tissue engineered niches with recruited DTCs in order to isolate the post dissemination environment. After transplantaion, 69% of scaffolds developed overt post-dissemination cancer growth, however 100% of scaffolds did not grow to a life-threatening critical size within twelve weeks. Adjuvant chemotherapy, while initially effective, did not prevent long-term DTC growth in scaffolds. Subjecting these transplanted niches to surgical resection via biopsy punch enhanced CD31, MMP9, Ly6G, and tumor burden compared to control scaffolds. Biopsy punching was able to rescue tumor incidence from prior chemotherapy. This model of serial transplantation of engineered DTC niches is a highly controllable and flexible method of establishing and systematically investigating the post-dissemination niche.

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Precision health for breast cancer metastasis: biomaterial scaffolds as an engineered metastatic niche to define, study, and monitor metastatic progression

Cited by 3 publications

References 9 publications

Engineered Niches to Analyze Mechanisms of Metastasis and Guide Precision Medicine

Engineered Niches to Analyze Mechanisms of Metastasis and Guide Precision Medicine

Breast cancer dormancy: need for clinically relevant models to address current gaps in knowledge

Inflammation drives tumor growth in an immunocompetent implantable metastasis model

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