FIGURE 1.

The experimental design and graphic mechanism. (A) Image‐guided biopsies were used to generate PDOs from liver metastatic colorectal cancers. PDOs were established from biopsies obtained before FO treatment in HA‐Coll sponge. Histopathology, molecular profiling, differentiation state, and protein analysis of PDOs and their parental tissues were characterized and compared. PDOs were used for FO drug screening, and ex vivo response to FO regimen was compared with clinical response. (B) The physical elasticity (E) of HA‐Coll sponge is close to that of the colorectal tissue, so that PDOs in HA‐Coll sponge could keep the similar expression level of lamin‐A as their parental tumor tissues. The lamin‐A protein could modulate the differentiation of colorectal epithelial cell to keep their epithelial state, which is important for their drug‐sensitivity on FO chemotherapeutic regimen. However, PDOs in Matrigel have lower expression level of lamin‐A and acquire mesenchymal characteristics, thereby they gradually form the drug resistance to FO regimen