Rethinking sympathetic regulation in cancer: From uniform signaling to context-dependent precision targeting

Accumulating evidence has established the sympathetic nervous system (SNS) as a critical regulator of tumor progression, making adrenergic signaling an attractive therapeutic target in oncology. Consequently, β-adrenergic blockade has been widely investigated as a strategy to inhibit cancer progression. However, recent advances in cancer neuroscience indicate that sympathetic regulation is considerably more complex than previously appreciated. Distinct adrenergic receptor subtypes, direct target cells, and tissue niches generate diverse biological outcomes, suggesting that indiscriminate inhibition of sympathetic signaling may not represent the optimal therapeutic approach. Here, we propose that the next challenge in cancer neuroscience is not whether sympathetic signaling should be targeted, but how it should be targeted. We introduce a context-dependent framework in which therapeutic strategies are guided by receptor subtype, direct target cell, and tissue-specific neural circuits rather than global sympathetic suppression. Finally, we discuss a future roadmap toward precision targeting and speculate that programmable neuromodulation may ultimately complement pharmacological intervention by enabling spatially and temporally selective control of tumor-associated neural circuits without influencing physiological functions.