HER2-Targeted PET Imaging and Therapy of Hyaluronan-Masked HER2-Overexpressing Breast Cancer

Pereira, Patrícia M. R.; Ragupathi, Ashwin; Shmuel, Shayla; Mandleywala, Komal; Viola, Nerissa T.; Lewis, Jason S.

doi:10.1021/acs.molpharmaceut.9b01091

Cited by 19 publications

(19 citation statements)

References 61 publications

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“…All five of these pathways are differentially active between the breast cancer cells and both epithelial and redirected cells further indicating that redirected cells are adopting a normal epithelial phenotype. CD44 is known to co-localize with HER2 preventing the binding of the anti-HER2 cancer treatment trastuzumab through steric hinderance [20,21]. CD44 expression is reduced in redirected cells and redirected cells lose tumor forming ability.…”

Section: Discussionmentioning

confidence: 99%

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

et al. 2020

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The influence of breast cancer cells on normal cells of the microenvironment, such as fibroblasts and macrophages, has been heavily studied but the influence of normal epithelial cells on breast cancer cells has not. Here using in vivo and in vitro models we demonstrate the impact epithelial cells and the mammary microenvironment can exert on breast cancer cells. Under specific conditions, signals that originate in epithelial cells can induce phenotypic and genotypic changes in cancer cells. We have termed this phenomenon "cancer cell redirection." Once breast cancer cells are redirected, either in vivo or in vitro, they lose their tumor forming capacity and undergo a genetic expression profile shift away from one that supports a cancer profile towards one that supports a non-tumorigenic epithelial profile. These findings indicate that epithelial cells and the normal microenvironment influence breast cancer cells and that under certain circumstances restrict proliferation of tumorigenic cells.

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Section: Discussionmentioning

confidence: 99%

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

et al. 2020

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“…Metabolic imaging for monitoring HER2-targeted therapy response Despite successful HER2-directed therapies, drug resistance inevitably develops in patients with HER2 + breast cancer [25,64,65]. ImmunoPET using isotope-labeled HER2 affibody-like ( 89 Zr)labeled trastuzumab [66] could non-invasively reflect the HER2 expression level to select patients who could benefit from HER2-targeted therapy. However, the diversity of the resistance mechanism to HER2-targeted therapy requires more monitoring methods.…”

Section: Diagnostic Methods To Detect Early Response To Pi3k Pathway Inhibitorsmentioning

confidence: 99%

Integrating metabolic reprogramming and metabolic imaging to predict breast cancer therapeutic responses

Liu

Zhou

Song

2021

Trends in Endocrinology & Metabolism

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Metabolic reprogramming is not only an emerging hallmark of cancer, but also an essential regulator of cancer cell adaptation to the microenvironment. Metabolic imaging targeting metabolic signatures has been widely used for breast cancer diagnosis. However, limited implications have been explored for monitoring breast cancer therapy response, although metabolic plasticity is notably associated with therapy resistance. In this review, we focus on the metabolic alterations upon breast cancer therapy and their potential for evaluating breast cancer therapeutic responses. We summarize the metabolic network and regulatory changes upon breast cancer therapy in terms of cancer pathological and genetic differences and discuss the implications of metabolic imaging with various probes in selecting target beneficiaries for precision treatment. Key metabolic reprogramming of breast cancer in response to therapyReprogramming of glucose metabolism upon breast cancer therapy Drug-resistant breast cancer cells are able to reprogram glucose metabolism to adapt to the stress induced by drug treatment (Figure 1). For example, breast cancer cells resistant to lapatinib, a dual inhibitor of dermal growth factor receptor (EGFR) and HER2, recover the Highlights Reprogramming of metabolic pathways is pivotal for the adaptation and resistance to antitumor treatments in breast cancer.Metabolic changes upon treatment are superior to single timepoint metabolic signals in monitoring breast cancer therapeutic response.Cancer genetic and metabolic heterogeneity need to be fully integrated to precisely predict breast cancer response to different treatments.Metabolic imaging guided usage of anticancer drugs is critical for precise treatment in breast cancer.

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“…Trastuzumab-resistant JIMT1 breast cancer cells were treated with hyaluronidase and 4-methylumbelliferone Degradation of hyaluronan and inhibition of its synthesis were achieved by treating trastuzumab-resistant JIMT1 breast cancer cells with hyaluronidase and 4-methylumbelliferone to degrade hyaluronan and inhibit its synthesis. This combined treatment resulted in the increased uptake of a radiolabelled trastuzumab conjugate ([ 89 Zr]Zr-trastuzumab) and the enhanced efficacy of trastuzumab in JIMT1 xenografts ( Pereira et al, 2020 ).…”

Section: Extracellular Barriersmentioning

confidence: 99%

Therapeutic antibodies – natural and pathological barriers and strategies to overcome them

Ojaimi

Blin

Lamamy

et al. 2022

Pharmacology & Therapeutics

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Antibody-based therapeutics have become a major class of therapeutics with over 120 recombinant antibodies approved or under review in the EU or US. This therapeutic class has experienced a remarkable expansion with an expected acceleration in 2021–2022 due to the extraordinary global response to SARS-CoV2 pandemic and the public disclosure of over a hundred anti-SARS-CoV2 antibodies. Mainly delivered intravenously, alternative delivery routes have emerged to improve antibody therapeutic index and patient comfort. A major hurdle for antibody delivery and efficacy as well as the development of alternative administration routes, is to understand the different natural and pathological barriers that antibodies face as soon as they enter the body up to the moment they bind to their target antigen. In this review, we discuss the well-known and more under-investigated extracellular and cellular barriers faced by antibodies. We also discuss some of the strategies developed in the recent years to overcome these barriers and increase antibody delivery to its site of action. A better understanding of the biological barriers that antibodies have to face will allow the optimization of antibody delivery near its target. This opens the way to the development of improved therapy with less systemic side effects and increased patients’ adherence to the treatment.

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HER2-Targeted PET Imaging and Therapy of Hyaluronan-Masked HER2-Overexpressing Breast Cancer

Cited by 19 publications

References 61 publications

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

Induction of phenotypic changes in HER2-postive breast cancer cells in vivo and in vitro

Integrating metabolic reprogramming and metabolic imaging to predict breast cancer therapeutic responses

Therapeutic antibodies – natural and pathological barriers and strategies to overcome them

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