Abstract Cancer-associated fibroblasts (CAFs) fundamentally impact on characteristics of tumor cells and are concerned with therapy resistance via extensive interplay with cancer cells and other stromal components. In addition, inherent plasticity and multifunctionality of CAFs enable cancer cells to cultivate them, leading to dynamic changes in the population of CAFs in a context-dependent manner. Despite CAFs have long been regarded as a key participant in cancer development and therefore an appealing therapeutic target, most clinical trials targeting CAFs end in failure, and even accelerate progression of cancers, indicating that dynamic complicated identity and function of CAFs far exceed the current view. Accordingly, analyzing the heterogeneous subgroups and different functions of CAFs in a context dependent mode is of great significance. To ascertain the functional interactions between CAFs and cancer cells, various three-dimensional co-culture models of organoid with CAFs and cancer cells from murine or human have been successfully established. In the review, we recapitulate the proposed methods for cultivating organoids consisted of tumor cells and CAFs as well as molecular mechanisms involving in regulating variety of CAF subgroups. Current strategies targeting tumor-promoting CAFs selectively are also discussed, offering perception and perspectives for scientific investigation and clinical trials concerning various methods targeting CAFs.
Wang et al. (2026) studied this question.