Breast cancer organoids model treatment response of HER2 targeted therapy in HER2-mutant breast cancer

Li, X.; Pan, Baishen; Ma, Jia; Zhao, Zihan; Li, M.

doi:10.1093/annonc/mdz268.022

Cited by 1 publication

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“…For instance, triple negative breast cancers grow in immunodeficient mouse models, but most luminal estrogen receptor positive and human epidermal growth factor receptor 2 positive breast xenografts cannot grow (Sflomos et al, 2016, Dobrolecki et al, 2016. However, there are reports of growing 7 these subtypes in three-dimensional cell culture as organoids (Li et al, 2019, Campaner et al, 2020 which is important since organoids have been shown to more closely mimic in vivo responses compared to 2D cell culture (Bleijs et al, 2019, Yang et al, 2020. In addition, tumor organoids can accurately recapitulate in vivo drug responses, simplify experiments, and save time and money (Bleijs et al, 2019, Fan et al, 2019, Sasmita and Wong 2018.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Assessment of Hydroxychloroquine in Breast Cancer

Eaton

Gustafson

2021

J Pharmacol Exp Ther

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Hydroxychloroquine (HCQ) is being tested in a number of human clinical trials to determine the role of autophagy in response to standard anticancer therapies. However, HCQ pharmacodynamic responses are difficult to assess in patients and preclinical studies in mouse models are equivocal with regard to HCQ exposure and inhibition of autophagy. Here, pharmacokinetic (PK) assessment of HCQ in non-tumor bearing mice following intraperitoneal (IP) dosing established 60 mg/kg as the human equivalent dose of HCQ in mice. Autophagy inhibition, cell proliferation, and cell death were assessed in 2D cell culture and 3D tumor organoids in breast cancer. Mice challenged with breast cancer xenografts were then treated with 60 mg/kg HCQ via IP dosing and subsequent PK and pharmacodynamic (PD) responses were assessed. Although autophagic flux was significantly inhibited in cells irrespective of autophagy dependency status, autophagy dependent tumors had decreased cell proliferation and increased cell death at earlier time points compared to autophagy independent tumors. Overall, this study shows that 2D cell culture, 3D tumor organoids, and in vivo studies produce similar results and in vitro studies can be used as surrogates to recapitulate in vivo antitumor responses of HCQ.

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