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Graphical abstract, Even given recent advances in nanomedicine development of breast cancer treatment in recent years and promising results in pre-clinical models, cancer nanomedicines often fail at the clinical trial stage. Limitations of conventional in vitro models include the lack of representation of the stromal population, the absence of a three-dimensional (3D) structure, and a poor representation of inter-tumor and intra-tumor heterogeneity. Herein, we review those cell culture strategies that aim to overcome these limitations, including cell co-cultures, advanced 3D cell cultures, patient-derived cells, bioprinting, and microfluidics systems. The in vivo evaluation of nanomedicines must consider critical parameters that include the enhanced permeability and retention effect, the host's immune status, and the site of tumor implantation. Here, we critically discuss the advantages and limitations of current in vivo models and report how the improved selection and application of breast cancer models can improve the clinical translation of nanomedicines.

Objective Type 1 diabetes (T1D) is known to be caused by Th1 cell-dependent autoimmunity. Recently, we reported that TYK2 promoter variant serves as a putative virus-induced diabetes susceptibility gene associated with deteriorated interferon-dependent antiviral response. TYK2 is also related to HIES, that is, Th2 cell-dependent. Therefore, TYK2 promoter variant may be also associated with the pathogenesis of T1D, modulating Th1/Th2 balance. Research Design and Methods We assessed the association between anti- GAD Ab, IgE levels, and TYK2 promoter variant among 313 T1D patients, 184 T2D patients, and 264 YH controls in the Japanese. Results T1D patients had elevated IgE (median, 56.7 U/ml; p, Highlights • T1D can be subtyped into 4 groups based on anti-GAD Ab, IgE levels and TYK2 promoter variant. • Only one subtype, without anti-GAD Ab or elevated IgE, was associated with TYK2 promoter variant and flu-like syndrome. • Profiling of T1D by anti-GAD Ab and IgE levels is useful to realize the variable immuno-pathogenesis of T1D. Since TYK2 gene is associated with T1D and HIES, we assessed the association between anti-GAD Ab, IgE levels, and TYK2 promoter variant in patients with T1D. Consequently, T1D can be subtyped into 4 distinct groups based on these clinical laboratory and genetic markers. Only those patients without anti-GAD Ab or elevated IgE were associated with TYK2 promoter variant and with flu-like syndrome at the diabetes onset, suggestive of association with virus-induced diabetes. This study describes the usefulness of subtyping of T1D with variable immunological bases and provides a clue to delineate the pathogenesis of T1D.