イオンチャネルと癌

Ion channels involved in cancer (click on image to enlarge)

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 First author: Schupp et al., 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 First author: Yang et al., 2016

Reports

  • 詳細 Cav1.2 on Qube 384
    Year: 2017 First author: Schupp, M
  • 詳細 CHO Cav1.2 on QPatch (ChanTest)
    Year: 2011 First author: Friis et al., 2011

Kca

Papers

  • 詳細 Inhibition of the potassium channel KCa3.1 by senicapoc reverses tactile allodynia in rats with peripheral nerve injury
    Year: 2016 First author: Staala et al., 2016
  • 詳細 New positive Ca2+-activated K+ channel gating modulators with selectivity for KCa3.1
    Year: 2014 First author: Coleman et al., 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 First author: Korsgaard et al., 2009
  • 詳細 Development of a QPatch Automated Electrophysiology Assay for Identifying KCa3.1 Inhibitors and Activators
    Year: 2013 First author: Jenkins et al., 2013

Reports

  • 詳細 HEK293-KCa on QPatch
    Year: 2008 First author: Jacobsen et al., 2008
  • 詳細 The intermediate conductance Ca2+ – activated K+ channel on Qube 384
    Year: 2017 First author: Sauter

Kv

Posters

  • 詳細 Enhancing throughput with multiple cell lines per well
    First author: Olsen et al., 2006
  • 詳細 Enhancing throughput with multiple cell lines per well with the QPatch HTX
    Year: 2010 First author: Olsen et al., 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 First author: Schupp et al., 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 First author: Chen, Q

Papers

  • 詳細 A Novel Modulator of Kv3 Potassium Channels Regulates the Firing of Parvalbumin-Positive Cortical Interneurons
    Year: 2015 First author: Rosata-Siri et al., 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 First author: Al-Sabi et al., 2017
  • 詳細 Arrangement of Kv1 α subunits dictates sensitivity to tetraethylammonium
    Year: 2010 First author: Al-Sabi et Al
  • 詳細 Isoindolinone compounds active as Kv1.5 blockers identified using a multicomponent reaction approach
    Year: 2015 First author: Kajanus et al.
  • 詳細 Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brainstem neurons
    Year: 2016 First author: Brown et al., 2016
  • 詳細 Porphyrin derivatives as potent and selective blockers of neuronal Kv1 channels
    Year: 2014 First author: Daly et al., 2014
  • 詳細 Chemoselective tarantula toxins report voltage activation of wild-type ion channels in live cells
    Year: 2014 First author: Tilleya et al., 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 First author: Ariasa et al., 2016
  • 詳細 New positive Ca2+-activated K+ channel gating modulators with selectivity for KCa3.1
    Year: 2014 First author: Coleman et al., 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 First author: Huang
  • 詳細 Rapid generation of cells for ion channels assays: Efficient, large scale transfection using the MaxCyte STX
    First author: Brady et al.
  • 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 First author: Korsgaard et al., 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 First author: Chrovian et Al.

Reports

  • 詳細 CHO-Kv1.5 Voltage-gated potassium channels on QPatch
    Year: 2009 First author: Jensen et al., 2009
  • 詳細 CHO-KvLQT1 minK on QPatch
    Year: 2011 First author: Olsen et al., 2011

Nav1.5, Nav1.7

Posters

  • 詳細 CHO-hNav1.7 assay on Qube pharmacology, biophysical characterization and the effect of internal fluoride
    Year: 2017 First author: Sauter et al., 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 First author: Schupp et al., 2016
  • 詳細 Nav1.5 use-dependent blockers on QPatch X
    Year: 2012 First author: Jacobsen et al., 2012
  • 詳細 Use- and state-dependent Nav1.5 blockers on QPatch X and in vivo and in vitro assays
    Year: 2010 First author: Jensen et al., 010
  • 詳細 Rapid generation of cells for ion channels assays: Efficient, large scale transfection using the MaxCyte STX
    First author: Brady et al.
  • 詳細 Enhancing throughput with multiple cell lines per well
    First author: Olsen et al., 2006
  • 詳細 “Clip Detecting” with series resistance compensation using an automated patch clamp system
    Year: 2012 First author: Løjkner et al., 2012
  • 詳細 Biophysical and pharmacological characterization of multiple Nav subtypes on Qube
    Year: 2016 First author: Lindqvist et Al
  • 詳細 Biophysical and pharmacological profiling of multiple Nav subtypes on QPatch HT
    Year: 2016 First author: Lindqvist et al., 2016

Papers

  • 詳細 High-Throughput Screening of Nav1.7 Modulators Using a Giga-Seal Automated Patch Clamp Instrument
    Year: 2016 First author: Chambers et al., 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 First author: Klint et al., 2015
  • 詳細 Engineering Highly Potent and Selective Microproteins Against Nav1.7 Sodium Channel for Treatment of Pain
    Year: 2016 First author: Shcherbatko et al., 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 First author: Korsgaard et al., 2009
  • 詳細 Use- and state-dependent Nav1.5 blockers on QPatch X and in vivo and in vitro assays
    Year: 2010 First author: Jensen et al., 010
  • 詳細 MICE Models: Superior to the HERG Model in Predicting Torsade de Pointes
    Year: 2013 First author: Kramer et al., 2013
  • 詳細 A new classifier-based strategy for in-silico ion-channel cardiac drug safety assessment
    Year: 2015 First author: Mistry et al., 2015
  • 詳細 Screening system for drug-induced arrhythmogenic risk combining a patch clamp and heart simulator
    Year: 2015 First author: Okada et al., 2015

Reports

  • 詳細 CHO-Nav1.5 on QPatch
    Year: 2012 First author: Olsen
  • 詳細 Use- and state-dependent Nav1.5 blockers on QPatch X and in vivo and in vitro assays
    Year: 2010 First author: Jensen et al., 010
  • 詳細 Voltage-gated sodium channels on QPatch 16
    Year: 2012 First author: Olsen 2012
  • 詳細 Cor.At cells embryonic stem cell derived cardiomyocytes on QPatch
    Year: 2009 First author: Schrøder et al., 2009

TRP

Posters

  • 詳細 TRP’ing in multi-hole mode
    Year: 2010 First author: Jacobsen et al., 2010

Papers

  • 詳細 The development of automated patch clamp assays for canonical transient receptor potential channels TRPC3, 6, and 7
    Year: 2014 First author: McPate et Al.
  • 詳細 QPatch: the missing link between HTS and ion channel drug discovery.
    Year: 2009 First author: Mathes
  • 詳細 Study of TRP Channels by Automated Patch Clamp Systems
    Year: 2010 First author: Sunesen et al., 2010

Reports

  • 詳細 HEK293-TRPV1 on QPatch
    Year: 2011 First author: Jacobsen et al., 2011
  • 詳細 TRPM8 cold sensitive ion channels
    Year: 2012 First author: Jensen

TMEM

Papers

  • 詳細 Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling
    Year: 2013 First author: Britschgi, A

Reports

  • 詳細 TMEM16A on Qube
    Year: 2017 First author: Sauter, D
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