イオンチャネルと癌
細胞膜を通過するイオンの輸送は、細胞体積調節、細胞移動、細胞周期の進行、細胞増殖および細胞死などの腫瘍細胞の機能において重要な役割を果たします。これらの機能は腫瘍細胞の生存や転移において重要です。
増殖因子やホルモンによって上方制御され、その結果腫瘍の生存に決定的に重要となるような腫瘍関連のイオンチャネルは、治療方法探索の対象となり得ます。ただし、他の細胞（例えば心臓再分極に関与するチャネル）の機能に重要な影響を与えず、なおかつ腫瘍増殖の抑制に効果的なイオンチャネルのみが、腫瘍治療へ適用可能と考えられます。また、腫瘍治療の標的となり得るイオンチャネルは、腫瘍細胞以外の細胞の、増殖および生存にも関与する可能性があります。
いくつかのイオンチャネルは、現在、腫瘍形成に関与する対象として、もしくは抗癌剤の潜在的標的として研究されています。
腫瘍関連研究の論文例：
Rao et Al 2015. Voltage-Gated Ion Channels in Cancer Cell Proliferation (LINK)
Litan and Langhans 2015. Cancer as a channelopathy: ion channels and pumps in tumor development and progression (LINK)
Dowd et Al 2017 Ion Channels in Breast Cancer: From Signaling to Therapy (LINK)
…or check out a search on ion channel and cancer (HERE)
See below for QPatch and Qube publications on selected cancer relevant ion channels
Calcium Channels
- Cav1.2
- Cav3.2
Potassium channels, Calcium activated
- Kca1.1
- Kca3.1
Potassium channels, voltage-gated
- Kv1.3
- Kv1.5
- Kv11.1 (hERG)
Sodium channels, voltage-gated
- Nav1.5
- Nav1.7
TRP Channels
- TRPC6
- TRPM4
- TRPM8
- TRPV1
- TRPV6
Calcium activated chloride channel
- TMEM16A
Cav
Posters
- 詳細 Qube as a tool for assay optimization of CiPA cells and protocols by using multiple IC, EC solutions and hERG, Nav1.5 and Cav1.2 on the same QChip Year: 2016
Papers
- 詳細 The Snake with the Scorpion’s Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake Year: 2016
Reports
Kca
Posters
- 詳細 Wnt peptides control mammalian cancer cell membrane potential Year: 2018
Papers
- 詳細 Inhibition of the potassium channel KCa3.1 by senicapoc reverses tactile allodynia in rats with peripheral nerve injury Year: 2016
- 詳細 New positive Ca2+-activated K+ channel gating modulators with selectivity for KCa3.1 Year: 2014
- 詳細 Automated Planar Electrode Electrophysiology in Drug Discovery: Examples of the Use of QPatch in Basic Characterization and High Content Screening on Nav, KCa2.3, and Kv11.1 Channels Year: 2009
- 詳細 Development of a QPatch Automated Electrophysiology Assay for Identifying KCa3.1 Inhibitors and Activators Year: 2013
Reports
Kv
Posters
- 詳細 Enhancing throughput with multiple cell lines per well
- 詳細 Enhancing throughput with multiple cell lines per well with the QPatch HTX Year: 2010
- 詳細 Qube as a tool for assay optimization of CiPA cells and protocols by using multiple IC, EC solutions and hERG, Nav1.5 and Cav1.2 on the same QChip Year: 2016
- Simple and Effective Generation of Cell-based Assays for Ion Channels, Transporters, and Kinase Screening in Biologically Relevant Cells Using Scalable Transient Transfection Year: 2014
Papers
- 詳細 A Novel Modulator of Kv3 Potassium Channels Regulates the Firing of Parvalbumin-Positive Cortical Interneurons Year: 2015
- 詳細 A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves that Improves their Impaired Axonal Conduction Year: 2017
- 詳細 Arrangement of Kv1 α subunits dictates sensitivity to tetraethylammonium Year: 2010
- 詳細 Isoindolinone compounds active as Kv1.5 blockers identified using a multicomponent reaction approach Year: 2015
- 詳細 Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brainstem neurons Year: 2016
- 詳細 Porphyrin derivatives as potent and selective blockers of neuronal Kv1 channels Year: 2014
- 詳細 Chemoselective tarantula toxins report voltage activation of wild-type ion channels in live cells Year: 2014
- 詳細 Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content Year: 2016
- 詳細 New positive Ca2+-activated K+ channel gating modulators with selectivity for KCa3.1 Year: 2014
- 詳細 Synthesis and biological evaluation of novel 6,11-dihydro-5H-benzo[e]pyrimido- [5,4-b][1,4]diazepine derivatives as potential c-Met inhibitors Year: 2017
- 詳細 Rapid generation of cells for ion channels assays: Efficient, large scale transfection using the MaxCyte STX
- 詳細 Automated Planar Electrode Electrophysiology in Drug Discovery: Examples of the Use of QPatch in Basic Characterization and High Content Screening on Nav, KCa2.3, and Kv11.1 Channels Year: 2009
- 詳細 A dipolar cycloaddition reaction to access 6-methyl-4,5,6,7-tetrahydro-1H-[1,2,3]triazolo[4,5-c]pyridines enables the discovery synthesis and preclinical profiling of a P2X7 antagonist clinical candidate Year: 2017
Reports
Nav1.5, Nav1.7
Posters
- 詳細 CHO-hNav1.7 assay on Qube pharmacology, biophysical characterization and the effect of internal fluoride Year: 2017
- 詳細 Qube as a tool for assay optimization of CiPA cells and protocols by using multiple IC, EC solutions and hERG, Nav1.5 and Cav1.2 on the same QChip Year: 2016
- 詳細 Nav1.5 use-dependent blockers on QPatch X Year: 2012
- 詳細 Use- and state-dependent Nav1.5 blockers on QPatch X and in vivo and in vitro assays Year: 2010
- 詳細 Rapid generation of cells for ion channels assays: Efficient, large scale transfection using the MaxCyte STX
- 詳細 Enhancing throughput with multiple cell lines per well
- 詳細 “Clip Detecting” with series resistance compensation using an automated patch clamp system Year: 2012
- 詳細 Biophysical and pharmacological characterization of multiple Nav subtypes on Qube Year: 2016
- 詳細 Biophysical and pharmacological profiling of multiple Nav subtypes on QPatch HT Year: 2016
Papers
- 詳細 High-Throughput Screening of Nav1.7 Modulators Using a Giga-Seal Automated Patch Clamp Instrument Year: 2016
- 詳細 Rational engineering defines a molecular switch that is essential for activity of spider-venom peptides against the analgesics target Nav1.7 Year: 2015
- 詳細 Engineering Highly Potent and Selective Microproteins Against Nav1.7 Sodium Channel for Treatment of Pain Year: 2016
- 詳細 Automated Planar Electrode Electrophysiology in Drug Discovery: Examples of the Use of QPatch in Basic Characterization and High Content Screening on Nav, KCa2.3, and Kv11.1 Channels Year: 2009
- 詳細 Use- and state-dependent Nav1.5 blockers on QPatch X and in vivo and in vitro assays Year: 2010
- 詳細 MICE Models: Superior to the HERG Model in Predicting Torsade de Pointes Year: 2013
- 詳細 A new classifier-based strategy for in-silico ion-channel cardiac drug safety assessment Year: 2015
- 詳細 Screening system for drug-induced arrhythmogenic risk combining a patch clamp and heart simulator Year: 2015
Reports
TRP
Posters
- 詳細 TRP’ing in multi-hole mode Year: 2010
Papers
Reports
TMEM
Papers
- 詳細 Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling Year: 2013
Reports
- 詳細 TMEM16A on Qube Year: 2017