A promising, yet still under development approach to cancer treatment is based on the idea of differentiation therapy (DTH). Most tumours are characterized by poorly differentiated cell populations exhibiting a marked loss of traits associated to communication and tissue homeostasis. DTH has been suggested as an alternative (or complement) to cytotoxic-based approaches, and has proven successful in some specific types of cancer such as acute promyelocytic leukemia (APL). While novel drugs favouring the activation of differentiation therapies are being tested, several open problems emerge in relation to its effectiveness on solid tumors. Here we present a mathematical framework to DTH based on a well-known ecological model used to describe habitat loss. The models presented here account for some of the observed clinical and in vitro outcomes of DTH, providing relevant insight into potential therapy design. Furthermore, the same ecological approach is tested in a hierarchical model that accounts for cancer stem cells, highlighting the role of niche specificity in CSC therapy resistance. We show that the lessons learnt from metapopulation ecology can help guide future developments and potential difficulties of DTH.

一种有前途但仍在发展中的癌症治疗方法是基于分化治疗（DTH）的思想。大多数肿瘤的特点是分化程度低的细胞群表现出与通讯和组织动态平衡有关的特征明显丧失。有人建议将DTH替代（或补充）基于细胞毒性的方法，并已证明在某些特定类型的癌症（例如急性早幼粒细胞白血病（APL））中是成功的。尽管正在测试有利于激活分化疗法的新药，但有关其对实体瘤的有效性方面出现了一些开放性问题。在这里，我们基于用于描述栖息地丧失的著名生态模型，为DTH提出了数学框架。这里介绍的模型解释了DTH在临床和体外观察到的一些结果，提供有关潜在疗法设计的相关见解。此外，在解释癌症干细胞的分层模型中测试了相同的生态方法，强调了利基特异性在CSC治疗耐药性中的作用。我们表明，从种群生态学中吸取的教训可以帮助指导DTH的未来发展和潜在困难。