Frontiers in Molecular Biosciences |21 March 2023, Volume 10 - 2023 | doi.org/10.3389/fmolb.2023.1178488
Subramanyam Dasari, Prabhakar Pitta Venkata,Uday Pratap, Ram Mohan Ram Kumar
More than 90% of cancer mortality is due to metastasis; however, the essential mechanisms driving this multistep process, from the primary site to the development of metastatic cells at the secondary sites, remain tenuous. The communication between the cancer cells and the associated stromal cells starts at the stages of tumor formation and continues during growth, invasion, intravasation, and establishment at the secondary site called metastasis. This cross-talk between the cancer cells and stromal cells establishes a tumor microenvironment (TME). TME dynamically regulates cancer progression, promotes immune evasion, and influences the therapeutic outcome. Hence, strategies to therapeutically target the TME have emerged as a promising approach for standard-of-care therapies. The TME comprises the extracellular matrix (ECM); secreted molecules (growth factors, cytokines, chemokines, and extracellular vesicles); stromal cells such as cancer-associated fibroblasts (CAF), pericytes, endothelial cells, adipose cells, and mesenchymal cells; immune cells, including T and B lymphocytes; tumor-associated macrophages (TAM); dendritic cells (DC); natural killer (NK) cells; neutrophils; and the blood and lymphatic vascular networks, which are collectively enmeshed and in communication with each other and with the heterogeneous cancer cells themselves. Because of this complexity, various strategies have been developed to therapeutically target the TME. Despite the excellent advances that were made in the last decade, some improvements are still required at each stage of TME development and metastasis.
