English: Stromal cell types in early and late-stage tumors: (A) Initial tumor stages are characterized by the presence of inactive, non-invasive fibroblasts within the tumor microenvironment (TME). (B) Conditions like hypoxia initiate tumor-related inflammation and set off environmental signals that are involved in the paracrine communication cycle (including cytokines, chemokines, and growth factors) along with angiogenesis triggers (VEGF, PDGF-b, FGF, and EGF), leading to the alteration or transformation of stromal cells. These elements collectively contribute to the variation in stromal cell populations as the cancer progresses. (C) The release of cytokines and growth factors such as TGF-b, IL-6 by tumor cells leads to the activation of dormant fibroblasts. (D) These activated fibroblasts then evolve into secretory types that are adept at remodeling the extracellular matrix (ECM) and influencing the immune environment. These fibroblasts display increased growth and ECM production abilities (known as desmoplasia). Various aggressive subtypes of cancer-associated fibroblasts (CAF) identified in numerous cancers include antigen-presenting CAFs (apCAFs), inflammatory CAFs (iCAFs), and myofibroblastic CAFs (myCAFs). These subtypes are identified using single-cell RNA sequencing transcriptomics, named for their secreted factors and their functions within the TME. (E) Diverse endothelial cell types in tumor tissue: typical endothelial cells in central or peripheral tumor regions are referred to as tumor endothelial cells. Beyond the usual tip and stalk cells, several subgroups have been found that show genetic markers linked to breaking through the basement membrane (initiating metastasis), attracting immune cells, and creating an immunosuppressive TME. The discovery of such angiogenic entities with active angiogenic transcription factors and enzymes critical for angiogenesis presents a promising avenue for developing anti-angiogenic treatments.