The establishment of tumor microenvironment using biomimetic in vitro models that recapitulate key tumor hallmarks including the tumor supporting extracellular matrix (ECM) is in high demand for accelerating the discovery and preclinical validation of more effective anticancer therapeutics. To date, ECM‐mimetic hydrogels have been widely explored for 3D in vitro disease modeling owing to their bioactive properties that can be further adapted to the biochemical and biophysical properties of native tumors. Gathering on this momentum, herein the current landscape of intrinsically bioactive protein and peptide hydrogels that have been employed for 3D tumor modeling are discussed. Initially, the importance of recreating such microenvironment and the main considerations for generating ECM‐mimetic 3D hydrogel in vitro tumor models are showcased. A comprehensive discussion focusing protein, peptide, or hybrid ECM‐mimetic platforms employed for modeling cancer cells/stroma cross‐talk and for the preclinical evaluation of candidate anticancer therapies is also provided. Further development of tumor‐tunable, proteinaceous or peptide 3D microtesting platforms with microenvironment‐specific biophysical and biomolecular cues will contribute to better mimic the in vivo scenario, and improve the predictability of preclinical screening of generalized or personalized therapeutics.

中文翻译：

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用于生物工程高级 3D 肿瘤模型的蛋白质水凝胶

使用仿生体外模型建立肿瘤微环境，概括关键肿瘤特征，包括肿瘤支持细胞外基质（ECM），对于加速更有效的抗癌疗法的发现和临床前验证有很高的要求。迄今为止，ECM 模拟水凝胶已被广泛探索用于 3D 体外疾病模型，因为其生物活性特性可以进一步适应天然肿瘤的生化和生物物理特性。借助这一势头，本文讨论了已用于 3D 肿瘤建模的本质生物活性蛋白质和肽水凝胶的现状。首先，展示了重建此类微环境的重要性以及生成 ECM 模拟 3D 水凝胶体外肿瘤模型的主要考虑因素。还提供了针对用于建模癌细胞/基质串扰以及候选抗癌疗法的临床前评估的蛋白质、肽或混合 ECM 模拟平台的全面讨论。进一步开发具有微环境特异性生物物理和生物分子线索的肿瘤可调、蛋白质或肽 3D 微测试平台将有助于更好地模拟体内场景，并提高通用或个性化治疗的临床前筛选的可预测性。