Aguadé-Gorgorió Guim, Anderson Alexander R A, Solé Ricard
ISEM, Univ Montpellier, CNRS, IRD, Montpellier, France.
Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa, USA.
bioRxiv. 2024 Apr 26:2024.04.22.590504. doi: 10.1101/2024.04.22.590504.
Many advanced cancers resist therapeutic intervention. This process is fundamentally related to intra-tumor heterogeneity: multiple cell populations, each with different mutational and phenotypic signatures, coexist within a tumor and its metastatic nodes. Like species in an ecosystem, many cancer cell populations are intertwined in a complex network of ecological interactions. Most mathematical models of tumor ecology, however, cannot account for such phenotypic diversity nor are able to predict its consequences. Here we propose that the Generalized Lotka-Volterra model (GLV), a standard tool to describe complex, species-rich ecological communities, provides a suitable framework to describe the ecology of heterogeneous tumors. We develop a GLV model of tumor growth and discuss how its emerging properties, such as outgrowth and multistability, provide a new understanding of the disease. Additionally, we discuss potential extensions of the model and their application to three active areas of cancer research, namely phenotypic plasticity, the cancer-immune interplay and the resistance of metastatic tumors to treatment. Our work outlines a set of questions and a tentative road map for further research in cancer ecology.
许多晚期癌症对治疗干预具有抗性。这一过程从根本上与肿瘤内异质性相关：多个细胞群体，每个群体都具有不同的突变和表型特征，共存于肿瘤及其转移节点内。就像生态系统中的物种一样，许多癌细胞群体在复杂的生态相互作用网络中相互交织。然而，大多数肿瘤生态数学模型既无法解释这种表型多样性，也无法预测其后果。在此，我们提出广义Lotka-Volterra模型（GLV），一种描述复杂、物种丰富的生态群落的标准工具，为描述异质性肿瘤的生态学提供了一个合适的框架。我们开发了一个肿瘤生长的GLV模型，并讨论其诸如生长优势和多稳态等新出现的特性如何为该疾病提供新的理解。此外，我们讨论了该模型的潜在扩展及其在癌症研究的三个活跃领域的应用，即表型可塑性、癌症-免疫相互作用以及转移性肿瘤对治疗的抗性。我们的工作概述了一系列问题以及癌症生态学进一步研究的初步路线图。
