CA IX

Elevated CA IX expression has been associated with poor prognosis, tumor progression and aggressiveness. The plasma membrane associated dimeric glycoprotein catalyzes the reversible hydration of carbon dioxide to bicarbonate and a proton. CA IX is therefore an important component of the pH regulation systems, which are activated upon anaerobic glycolysis. Its main function during hypoxia is to preserve a neutral intracellular pH favorable for tumor growth and survival, while contributing to an acidic extracellular tumor micro-environment favorable for invasiveness.

 

Since CA IX is implicated in both extra – and intracellular pH regulation, we believe it is a potential therapeutic target.

Context

  • 13% of deaths in world due to cancer
  • Most cancers form solid tumors in tissues (e.g. head, neck, colon, breast, lung, liver, stomach)
  • Characteristics of tumors:
    low oxygen regions (hypoxia), heterogeneously spread within the tumor's acidification micro-environment
  • Poor response to radiotherapy, surgery and/or anticancer chemotherapy due to  large heterogeneity of tumor micro-evironment
 

Challenge

How to treat patients affected by solid tumors in a more effective way, without toxicity?
 
The solution: « Dual CA IX inhibitor »
 
An innovative anticancer drug, bifunctional, and targeting CA IX (receptor only present in tumors and hypoxia).
 
Bifunctional « CA IX inhibitor » drug
  •  CA IX specific (CA IX is a receptor present only in solid tumors, which eliminates acidity from the cell)
     
  •  Dual drug with two functional units, both having a therapeutic effect
    • one unit is CA IX specific 
    • the other unit sensitize tumors to radiations or other conventional drugs
       
  •  Targeted therapy
  •  Not toxic for normal tissues 

CAIX