Testing a Tiny Sensor in Mice to Find Colon Cancer Before it Spreads

Grantee: Liangliang Hao, PhD 
Institution: Massachusetts Institute of Technology
Area of Focus: Clinical Cancer Research, Nutrition, and Epidemiology
Grant Term: 2/1/2019 to 1/31/2021

The Challenge:
 Most deaths related to colorectal cancer (CRC) happen because the cancer spreads (metastasizes) from where it started to other places in the body. But commonly used diagnostic tests aren’t always able to find small tumors that are outside the colon or rectum (metastatic tumors). 

The Research: When tumor cells “want” to spread, they carve a path to a new location by trying to change the area around them (called the microenvironment). Liangliang Hao, PhD, hypothesized that the ideal time to find and treat the cancer is when the tumor cells are working to change their microenvironment.

She's developing a tiny tool that acts like a burglar alarm that may help diagnose CRC in mice early, before the cancer spreads. It’s called PRISM, and it includes sensors designed to detect changes in urine that could be related to the spread of cancer.

Hao injects this teeny probe into the mouse’s blood. Then, this is how it should work:

  • A protein in the tumor environment splits the probe, releasing a molecule called a reporter. 
  • If tumor cells start making more of that same protein, the environment becomes “looser,” meaning it’s easier for a cancer cell to move through and spread. 
  • That loosening “trips the alarm.” As a result, the reporter goes into the urine. A urine test identifies the presence of the reporter, showing that cancer is trying to spread.
  • The other molecule in PRISM senses the changed environment and builds up in tumor cells. Their increased numbers act like a beacon during a scan of the body, allowing researchers to easily see where the cancer is trying to grow.

The final piece of Hao’s project is working to find a treatment in mice that acts like police responding to a burglar alarm. The hope is that such a treatment will go only to where new cancer is trying to grow and stop it without affecting other parts of the body.  

Why Does It Matter? PRISM might make it possible to find cancer that’s trying to spread—before it’s spread. PRISM could also become an early player in precision diagnostics, which involves using diagnostic tests on patients to identify treatment options most likely to kill the cancer. 

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Last Revised: March 4, 2021