In silico cancer models have demonstrated great potential as a tool to improve drug design, optimise the delivery of drugs to target sites in the host tissue and, hence, improve therapeutic efficacy and patient outcome. However, there are significant barriers to the successful translation of in silicotechnology from bench to bedside. More precisely, the specification of unknown model parameters, the necessity for models to adequately reflectin vivoconditions, and the limited amount of pertinent validation data to evaluate models' accuracy and assess their reliability, pose major obstacles in the path towards their clinical translation. This review aims to capture the state-of-the-art in in silico cancer modelling of vascularised solid tumour growth, and identify the important advances and barriers to success of these models in clinical oncology. Particular emphasis has been put on continuum-based models of cancer since they - amongst the class of mechanistic spatio-temporal modelling approaches - are well-established in simulating transport phenomena and the biomechanics of tissues, and have demonstrated potential for clinical translation. Three important avenues in in silico modelling are considered in this contribution: first, since systemic therapy is a major cancer treatment approach, we start with an overview of the tumour perfusion and angiogenesis in silico models. Next, we present the state-of-the-art in silico work encompassing the delivery of chemotherapeutic agents to cancer nanomedicines through the bloodstream, and then review continuum-based modelling approaches that demonstrate great promise for successful clinical translation. We conclude with a discussion of what we view to be the key challenges and opportunities for in silico modelling in personalised and precision medicine.

中文翻译：

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从肿瘤灌注到药物输送和计算机模拟癌症模型的临床转化

计算机模拟癌症模型已显示出作为改进药物设计、优化药物向宿主组织中的靶位点的递送并因此提高治疗效果和患者结果的工具的巨大潜力。然而，硅技术从工作台到床边的成功转化存在重大障碍。更准确地说，未知模型参数的规范、模型充分反映体内条件的必要性以及评估模型准确性和评估其可靠性的相关验证数据数量有限，在其临床转化的道路上构成了主要障碍。本综述旨在捕捉血管化实体瘤生长的计算机模拟癌症模型的最新技术，并确定这些模型在临床肿瘤学中取得成功的重要进展和障碍。特别强调了基于连续介质的癌症模型，因为它们 - 在机械时空建模方法类别中 - 在模拟运输现象和组织的生物力学方面已经很好地建立起来，并且已经证明了临床转化的潜力。本贡献考虑了计算机模拟中的三个重要途径：首先，由于全身治疗是一种主要的癌症治疗方法，我们首先概述了计算机模型中的肿瘤灌注和血管生成。接下来，我们展示了最先进的计算机工作，包括通过血液将化学治疗剂输送到癌症纳米药物，然后回顾基于连续统的建模方法，这些方法展示了成功临床转化的巨大希望。最后，我们讨论了我们认为在个性化和精准医学中进行计算机建模的主要挑战和机遇。