The importance of fibrotic signaling in diseases beyond tissue fibrosis has been recognized. For examples, a well-documented phenomenon “Macrophage-Myofibroblast Transition” has been widely reported in kidney fibrosis (3), its implications in solid cancer has been started to be investigated nowadays (4). In this Research Topic, the clinical implications of fibrotic signaling in clinical solid cancers have been examined, where Chen et al. observed that intratumorally fibrosis and pseudo-capsule fibrosis are positively correlated to the disease progression of renal cell. While Shan et al. observed 10 fibrotic signaling (e.g. TLR4, Hedgehog, TGF-β, etc) are closely related to the biological activities of hepatocellular carcinoma cells after reviewing 264 related studies. Qin et al. has developed a new prognostic nomogram combined with desmoplastic reaction for predicting the progression of synchronous peritoneal metastasis in colorectal cancer patients.

Fibrotic signaling may contribute to pathogenesis that are beyond the end stage organ diseases. Myofibroblast formation is one of the critical steps for tissue scarring (5, 6) as well as tumor formation (4). Zhang et al. reported a pathogenic role of cancer-associated fibroblasts in the irradiation driven cancer progression. Cheng et al. further summarized the clinical implications of a myofibroblast-based targeting strategies for pancreatic cancer treatment. Besides, by transcriptome profiling of patient biopsies, Tulalamba et al. identified a Wnt signaling mediator FZD10 as potential biomarker for nasopharyngeal carcinoma recurrence and Chen et al. examined the clinical relevance of FGFR signaling in head and neck carcinoma. Sukphokkit et al. demonstrated a 3-dimensional culture system which can reformed the phenotype of cholangiocarcinoma cells compared to the conventional 2D system, may serve as an ideal platform for elucidating the underlying mechanisms as well as clinical potential of fibrotic signaling in cancer in vitro.

Indeed, a new study demonstrated that targeting of TGF-β/Smads signaling with a natural compound formula effectively overcome drug resistance of liver cancer cells via suppressing a multidrug resistant gene MDR1 (7). Here, Gao et al. reported Icaritin, an active component of the traditional Chinese herb Epimedium genus can inhibit cancer migration via targeting Akt/mTOR signaling of the cisplatin-resistant ovarian cancer cells in vitro. Ji et al. summarized the dynamics and therapeutic potentials of tumor-associated macrophages in solid cancer, such as a novel neuron type derived from “Macrophage to Neuron-like Cell Transition” in lung cancer ( Figure 1 ) (8). Single-cell RNA-sequencing allows researchers to dissect the TME in a cell-type specific manner, therefore the contributions of fibrotic signaling in the cancer immunity which was hidden in the conventional bulk sequencing at population level can be unmasked (9).

In conclusion, this Research Topic gathered the latest findings about fibrotic signaling in solid cancer, highlighting their clinical relevance and translational potential beyond fibrosis. We hope the collected articles can inspire both pre-clinical and translational researchers, clinical strategy targeting fibrotic signaling may eventually be developed for cancer therapy.

PT: Conceptualization, Funding acquisition, Resources, Visualization, Writing – original draft, Writing – review & editing. EL: Validation, Writing – review & editing. FM: Writing – review & editing. DZ: Writing – review & editing. CL: Writing – review & editing.