In vitro cancer models as an approach to identify targetable developmental phenotypes in cancer stem cells.
In vitro cancer models as an approach to identify targetable developmental phenotypes in cancer stem cells.
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DOI：
10.1007/s44164-023-00051-2
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发表时间：
2023
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影响因子：
--
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癌症治疗剂通常对患者具有高度毒性，并且它们通常在肿瘤中引起快速耐药性。最近的进展提出了一种潜在的新方法，我们可以通过两个重要的概念来改进这一点：（1）众多的途径改变集中在有限数量的癌症细胞表型上，以及（2）这些癌症细胞表型依赖于发育过程的重新激活，这些发育过程在成人组织中只有最低限度的活性。这提供了一个理论基础，追求的方法'drugging的表型'专注于靶向重新激活的细胞过程，从胚胎发育。在这篇概念论文中，我们涵盖了这些最新进展及其对开发新的癌症治疗方法的影响，这些方法可以避免患者毒性和获得性耐药性。然后，我们提出体外肿瘤和发育模型可以提供一种实验方法来识别和靶向发挥作用的特定发育过程，重点是重新激活驱动肿瘤进展和扩散的癌症干细胞中的发育过程。最终，目的是确定特定于发育表型的细胞过程，在癌症干细胞中重新激活，并且对肿瘤进展至关重要。治疗靶向这些细胞过程可能代表一种新的方法，即“药物治疗表型”，治疗肿瘤，同时避免患者毒性或获得治疗耐药性。
Cancer therapeutics are often highly toxic to the patient, and they often elicit rapid resistance in the tumour. Recent advances have suggested a potential new way in which we may improve on this, through two important concepts: (1) that multitudinous pathway alterations converge on a limited number of cancer cellular phenotypes, and (2) that these cancer cellular phenotypes depend on reactivation of developmental processes that are only minimally active in adult tissues. This provides a rationale for pursuing an approach of ‘drugging the phenotype’ focussed on targeting reactivated cellular processes from embryonic development. In this concepts paper, we cover these recent developments and their implications for the development of new cancer therapeutics that can avoid patient toxicity and acquired resistance. We then propose that in vitro tumour and developmental models can provide an experimental approach to identify and target the specific developmental processes at play, with a focus on the reactivation of developmental processes in the cancer stem cells that drive tumour progression and spread. Ultimately, the aim is to identify cellular processes that are specific to developmental phenotypes, are reactivated in cancer stem cells, and are essential to tumour progression. Therapeutically targeting these cellular processes could represent a new approach of ‘drugging the phenotype’ that treats the tumour whilst avoiding patient toxicity or the acquisition of therapeutic resistance.
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影响因子：
56.9
作者：
Jang, Wonyul;Puchkov, Dmytro;Haucke, Volker
通讯作者：
Haucke, Volker
影响因子：
11.2
作者：
Biddle, Adrian;Liang, Xiao;Mackenzie, Ian C.
通讯作者：
Mackenzie, Ian C.
影响因子：
4.6
作者：
Lim, Jormay;Thiery, Jean Paul
通讯作者：
Thiery, Jean Paul
影响因子：
64.8
作者：
Piskounova E;Agathocleous M;Murphy MM;Hu Z;Huddlestun SE;Zhao Z;Leitch AM;Johnson TM;DeBerardinis RJ;Morrison SJ
通讯作者：
Morrison SJ
影响因子：
11.1
作者：
Biddle A;Gammon L;Liang X;Costea DE;Mackenzie IC
通讯作者：
Mackenzie IC