A new study reveals that the liver’s cannabinoid receptors could be targeted tofight liver cancer in some patients; and it offers a way to predict whattreatments have the best chance of working.
Published in Cell Reports, the study reveals the metabolic processes by whichthe most common form of liver cancer, Hepatocellular carcinoma, is able togrow in oxygen-deprived, or hypoxic, conditions.
The researchers show how metabolic processes can be modeled to predict whichpatients will respond to drugs that block CB1 receptors, says Adil Mardinoglu, asystems biologist at Stockholm’s KTH Royal Institute of Technology.
“Our study explains why some cancer drugs are not effective in all patients, andwhat should be done before the treatment of a cancer,” Mardinoglu says.
“Even though it is the same cancer – in this case, liver cancer – it is vital tocharacterize the tumor before its treatment. Only 30 percent of patientsrespond to most clinically-used cancer drug available for the treatment of HCCdue in part to a lack of patient stratification.” Cancer cells have to modify theirmetabolism in order to meet the requirements for cellular proliferation.
One of those requirements is a constant supply of acetyl-CoA – a molecule thatplays a key role in many biochemical reactions and one of the main precursorsfor the building blocks of the cancer cells.
The research team found that these oxygen-deprived HCC cells thrive insteadon carbon produced by mitochondria – a double-membrane sub-unit of mostcells – which is where cellular respiration and energy production takes place.
Mathias Uhlén, Professor of Microbiology at KTH and the director of the HumanProtein Atlas program, says that the purpose of the open source researchdatabase is to “Drive the development of new diagnostics and drugs, but also toprovide basic insights in normal human biology. The current study is anexcellent example of the use of the open tsource information to explore humandiseases, such as liver cancer.” The body’s own marijuana-like substances, –called endocannabinoids – are known to increase the biosynthesis of fatty acidsin the liver by activating cannabinoid type 1 receptors.
CB1 receptors can be found in the brain, lungs, liver and kidney, and they areinvolved in a number of physiological processes, including mood, appetite, painsensation and memory.
The study found that the expression of these receptors increased in cancerousliver samples, when compared with cancer-free samples.