Susanna Greer: Outsmarting liver cancer with a double whammy

Susanna Greer, Chief Scientific Officer at the V Foundation for Cancer Research, published the following newsletter on LinkedIn:

”For this week’s Cool Cancer Find, we dive into an incredible paper from the V Foundation grantee Nabeel El-Bardeesy and his lab Mass General Hospital. To understand this study, imagine your body is like a city, busy, with different roads guiding city traffic. In our body the roads are our metabolic processes. But sometimes, a malfunctioning traffic signal interrupts the flow of traffic – in this case our troublemaker is a protein called FGFR2. It’s like a traffic light gone haywire, this time in the liver, telling the cells there (called hepatic bile ducts) to keep going, to grow uncontrollably, leading to a type of cancer called intrahepatic cholangiocarcinoma (ICC).

About 12-15% of ICC cases have this troublemaker FGFR2, which means they’re particularly sensitive to certain medications called FGFR inhibitors. These medications act like traffic cops, trying to stop FGFR2 from causing chaos in the liver cells.

However, there’s a catch, while these medications can slow down the troublemaker, they don’t always completely stop it. So, Nabeel El-Bardeesy and his team decided to dig deeper into how FGFR2 wreaks havoc and how these medications work. They found that FGFR2 not only encourages the liver cells to grow but also changes how they get their energy TO GROW. It’s like FGFR2 is whispering in the cells’ ears, telling them to gobble up lots of sugar (glucose) to fuel their rapid growth.

When they blocked FGFR2, they noticed something interesting: the liver cells couldn’t use as much sugar anymore. But instead of giving up, the cells found another way to get their energy. It’s like when your favorite pizza place closes, so you go to the smash burger joint next door instead.

This change in energy supply made the liver cells vulnerable in a different way. Nabeel El-Bardeesy and his team realized they could target this vulnerability by combining one drug with another treatment that focuses on the cancer cells’ energy factories, called mitochondria. Basically like hitting FGFR2 with a double whammy, blocking its signals and shutting down its backup energy source.

And here’s where this study gets even more fascinating. It’s possible that by making similar changes to our diets, changes like intermittent fasting (taking breaks from eating), could make some cancer treatments even more effective. Overall, this study uncovered some crucial insights into how FGFR2 causes trouble in liver cells and how we can outsmart it with targeted treatments and clever dietary tricks. If these strategies work as well as researchers translate them from the lab to the clinic, they will offer hope for patients battling this type of cancer, improving outcomes and quality of life.

Read Nabeel El-Bardeesy paper here: FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma | Nature Communications and follow his lab.”

Source: Susanna Greer/LinkedIn