Fibroproliferative conditions: the 3R approach bridging fibrosis and tumors

Soft-tissue fibroproliferative conditions (FPCs) affect many organs. All demonstrate the accumulation of (myo)fibroblasts and extracellular matrix. Currently, FPCs are classified according to the affected body site/organ. To promote research into the etiological mechanisms that drive pathological FPCs, we propose a new, more clinically grounded, FPC classification that is based on the intent and severity of the fibroproliferation. There are three categories: responsive, replacement, and reconstructive FPCs. Reconstructive FPCs (e.g., keloids) have quasi-neoplastic behaviors, including local invasiveness, and serve as a bridge between fibrosis and cancers. Comparisons of reconstructive FPCs to both cancers and the other FPC categories may help elucidate their pathogenic cellular properties, microenvironmental components, and intracellular-signaling mechanisms. Thus, the new FPC classification may promote research in the fibrosis field.