THBS1 and neoplasm: Since, altered extracellular binding proteins are known to modulate the TME, facilitating tumor invasion and migration (Insua-Rodríguez and Oskarsson, 2016; Gleissner et al., 2019), proteins like thrombospondin-1 (THBS1), which is a cytokine, and extracellular matrix proteins like EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1), fibulin-1 (FBLN1), and fibromodulin (FMOD) have well-known roles in tumor metastasis and drug resistance.