Neural invasion: a scenic trail for the nervous tumor and hidden therapeutic opportunity

Neural invasion (NI) is the invasion of cancer cells into nerves, influencing the pathological characteristics of malignant tumors. NI promotes metastasis and is associated with reduced survival of affected patients. Although known for decades, its prognostic and therapeutic implications have not been not much appreciated due to the scattered information available on its clinical complications. The use of multiple nomenclatures to describe NI also generated confusions among researchers to understand this pathological process. Here, we discuss the multiple classifications of NI and review its clinical complications. Recent findings of the regulatory roles of nerves on tumor growth have fuelled research in this field, and there has been several attempts to molecularly define the NI interface and the cancer cells involved. Therefore, in this review, we discuss the large datasets available to characterize the cancer cells in NI and also discuss the roles of Schwann cells and macrophages participating in NI.