Recognizing the significance of cancer-nerve crosstalk in advanced prostate cancer.

Advanced prostate cancer is one of the leading causes of cancer mortality in men and is often characterized by disease progression through therapeutic evasion followed by metastasis. Emerging evidence suggests that cancer-nerve crosstalk can influence the tumor microenvironment and promotes aggressive disease behavior. Neural infiltration within prostate tumors favors cancer-nerve crosstalk and therefore can establish a reciprocal exchange of growth factors, chemokines, neurotransmitters, and neurotrophic clues, which leads to tumor growth, therapy resistance, and the development of neuropathic symptoms. In advanced prostate cancer, neural infiltration mediated aberrant signaling within the cancer cells associated with poor clinical prognosis. Therapeutic intervention of locally advanced prostate cancer generates various neurological complications associated with peripheral neuropathy. Conversely, prolonged androgen receptor inhibition or chemotherapies in late-stage prostate cancer are associated with central nervous system complications such as altered neuronal activity, cognitive impairment, mood disturbances, and reduced quality of life. Therefore, preservation of neural integrity during prostate cancer therapy is in high demand to minimize nerve-related complications. However, conventional systemic therapies failed to prevent treatment-associated neural damage. Therefore, targeted therapies are in high demand to mitigate drug-related adverse effects. In this aspect, oncolytic viral therapy could represent a promising approach to aid selective killing of cancer cells. In the future, these could be emerging as viable candidates for first-line therapeutic intervention.