Role of the tumor microenvironment in cancer hallmarks and targeted therapy (Review)

Genetic alterations drive tumor onset and progression. However, the cross‑talk between tumor cells and the benign components of the surrounding stroma can also promote the initiation, progression and metastasis of solid tumors. These cellular and non‑cellular stromal components form the tumor microenvironment (TME), which co‑evolves with tumor cells. Their dynamic and mutualistic interactions are currently considered to be among the distinctive hallmarks of cancer. Biochemical and physical cues from the TME serve an essential role in regulating tumor onset and progression. They are also associated with resistance to treatment and poor prognosis in patients with cancer. Therefore, a deep understanding of the TME is vital for developing potent anticancer therapeutics and improving patient outcomes. The present review aims to review the biology of both cellular and non‑cellular constituents of the TME and novel findings regarding their contribution to core as well as emerging cancer hallmarks. The present review also describes key TME markers that are either targeted in interventional clinical trials or serve as promising potential anticancer therapies. Understanding TME components and their intercellular interactions is key toward identifying the mechanisms of progression and treatment resistance. Such understanding is of utmost significance for personalized and effective cancer therapy strategies.