Current research in cancer therapy aims to exploit efficient strategies to have long-lasting effects on tumors and to reduce or even revoke the chance of recurrence. Within the tumor stroma, O₂ and nutrients are abnormally distributed between various cells (preferentially for supplying cancer cells), the immune contexture is abnormally positioned (permissive essentially for cells exhibiting tumor-promoting capacity), the fibroblast and fibrotic content is abnormally distributed (presence of both extracellular matrix [ECM] stiffening and ECM-degrading factors both for tumor-promoting purposes), and the tumor vasculature is abnormally orchestrated (for hindering drug delivery and increasing the chance of tumor metastasis). Resistance is actually an adaptive response to an imbalance in the tumor ecosystem; thus, the key consideration for effective cancer therapy is to bring back the normal status in this ecosystem so as to reach the desired durable outcome. Vascular normalization, metabolic modulation (glucose delivery in particular), balancing cellular dispersion, and balancing the pH rate and O₂ delivery within the tumor microenvironment are suggested strategies to reverse abnormality within the tumor stroma.

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肿瘤生态系统的正常化：机遇与挑战

目前的癌症治疗研究旨在利用有效的策略对肿瘤产生持久的影响，并减少甚至消除复发的机会。在肿瘤基质内，O ₂和营养物质在各种细胞之间异常分布（优先供应癌细胞），免疫环境异常定位（基本上允许具有肿瘤促进能力的细胞），成纤维细胞和纤维化成分分布异常（同时存在细胞外基质 [ECM ] 用于促进肿瘤的硬化和 ECM 降解因子），并且肿瘤脉管系统异常协调（用于阻碍药物输送和增加肿瘤转移的机会）。耐药性实际上是对肿瘤生态系统失衡的一种适应性反应。因此，有效癌症治疗的关键考虑因素是使该生态系统恢复正常状态，以达到预期的持久结果。血管正常化，代谢调节（特别是葡萄糖输送），₂肿瘤微环境内的递送是逆转肿瘤基质内异常的建议策略。