Cancer Neuroscience of Kinase Inhibitors: On-Target Effects on the Nervous System

Area of Science:

• Cancer neuroscience
• Neuro-oncology
• Pharmacology

Background:

• Cancer neuroscience investigates the complex relationship between tumors and the nervous system.
• Kinase inhibitors are crucial anticancer drugs with known antitumor effects.

Purpose of the Study:

• To review the neurobiological and pharmacological effects of kinase inhibitors.
• To explore how these drugs modulate neural function.
• To highlight the mechanistic intersections between oncogenic and neural signaling.

Main Methods:

• Review of literature on kinase inhibitors targeting Trk, RET, VEGF/VEGFR, EGFR, and ALK pathways.
• Analysis of molecular mechanisms underlying drug effects on neural function.
• Examination of examples like TrkA-mediated pain and GDF15/RET-mediated appetite regulation.

Main Results:

• Certain kinase inhibitors possess significant antitumor activity.
• These inhibitors can modulate neural functions, including pain perception and appetite regulation.
• Specific pathways like TrkA and RET signaling are implicated in these neurobiological effects.

Conclusions:

• Kinase inhibitors can have unintended but significant effects on the nervous system.
• Understanding these off-target effects is crucial for cancer therapy.
• Elucidating tumor-nerve crosstalk through oncogenic and neural signaling advances cancer neuroscience.