Harnessing the Membrane Potential to Combat Cancer Progression

Area of Science:

• Cellular Electrophysiology
• Cancer Biology
• Tumor Microenvironment (TME)

Background:

• Plasma membrane potential (V_m) is essential for electrically excitable cells but also plays a functional role in nonexcitable cells, including cancer cells.
• Ion channels critically regulate V_m in cancer and stromal cells within the TME, suggesting V_m as a therapeutic target.
• V_m influences critical cancer hallmarks such as cell cycle progression, migration, invasion, immune infiltration, and pH regulation.

Purpose of the Study:

• To review recent advancements in understanding V_m regulation in tumors.
• To highlight the functional significance of V_m in cancer development and progression.
• To discuss the therapeutic potential of targeting V_m in cancer treatment.

Main Methods:

• Literature review focusing on V_m regulation in cancer.
• Analysis of the impact of V_m on small GTPase signaling (K-Ras, Rac1).
• Examination of V_m changes in the TME and their effect on immune cells.

Main Results:

• V_m alterations impact tumor development through small GTPase signaling.
• Changes in V_m within the TME affect immune cell function and cancer progression.
• Emerging evidence supports V_m as a viable therapeutic target, with compounds in clinical trials.

Conclusions:

• V_m is a significant regulator of cancer cell behavior and the TME.
• Targeting V_m via ion channel modulation or pulsed electric fields presents a promising therapeutic avenue.
• Further research is needed to fully elucidate V_m's role and optimize therapeutic strategies.