Antibodies Targeting K_VPotassium Channels: A Promising Treatment for Cancer

Abstract

Voltage-gated potassium channels are transmembrane proteins that allow flow of potassium across the membrane to regulate ion homeostasis, cell proliferation, migration, cell volume, and specific processes such as muscular contraction. Aberrant function or expression of potassium channels can underlie pathologies ranging from heart arrhythmia to cancer; the expression of potassium channels is altered in many types of cancer and that alteration correlates with malignancy and poor prognosis. Targeting potassium channels therefore constitutes a promising approach for cancer therapy. In this review, we discuss strategies to target a particular family of potassium channels, the voltage-gated potassium channels (K V) where a reasonable structural understanding is available. We also discuss the possible obstacles and advantages of such a strategy.

Overcoming challenges of HERG potassium channel liability through rational design: Eag1 inhibitors for cancer treatment

“…In contrast, the homologous regions of HERG face outward. This could reflect a tilting of that region during gate opening that is inhibited by mAb56 binding 232 . Although it did not show any effects on ionic permeation through Eag1, mAb62 exhibited a promising application as diagnostic tools or/and to deliver drugs as Cy5.5‐labeled mAb62 specifically bound and accumulated at tumor sites in vivo for at least 1 week, also drug‐activating enzyme β‐ d ‐galactosidase conjugated mAb62‐β‐gal bound to the tumor site and the enzyme galactosidase remained active in vivo 233 .…”

Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

“…Antibodies or small molecules that target tumor-specific isoforms may represent a way to increase the sensitivity and specificity of ion channel-targeted therapies in cancer. An example is the highly selective monoclonal antibody against the oncogenic Kv 10.1 potassium channel, which has been demonstrated to inhibit tumor growth both in xenograft models of human melanoma cells and in xenografted human pancreatic cancer [209]. Antibodies or fragments against ion channels might be also useful for cancer diagnosis [210].…”

Potassium Channels as a Potential Target Spot for Drugs

“…The expression pattern depends on the compartment and/or conditions like gravid or not in the uterus and part of lent blood vessels. This heteromultimerization seems to modulate Kv current expression, sensitivity to various substances, as well as biophysical properties of channels such as inactivation [14][15][16][17][18]. Further, research shows that the most important isoforms for the proliferation, activation, migration, and apoptosis of tumor cells are Kv1.3, Kv1.5, Kv2.1, Kv41, Kv9.3, Kv10.1, and Kv11.1 [19].…”

“…In cancer cells, K channel activity regulates cell proliferation, resistance to apoptotic cell death, tumor angiogenesis, invasiveness, and metastatic spread. Moreover, being expressed in cells of the tumor microenvironment, K channels can also modulate the immune/inflammatory response, which contributes to the drive of cancer establishment and progression [18,58]. After many years of studies, some K channels are emerging as novel cancer biomarkers, to be employed to stratify patients for either prognostic or predictive purposes [59].…”