Grantee: Christopher Maher, PhD
Institution: Washington University School of Medicine in St. Louis
Area of Focus: RNA Mechanisms in Cancer
Term: 07/01/2017 to 06/30/2021
“For decades, researchers focused on how genes that make proteins contribute to cancer. More recently, we identified a long non-coding RNA, which carries genetic code that doesn’t result in a protein, that has the potential to help doctors diagnosis and treat metastatic colon cancer. Our lab is dedicated to understanding how these RNAs contribute to metastatic colon cancer to help guide the development of new treatments for this most deadly stage of the disease.”–Christopher Maher, PhD
The Challenge: Approximately 50% of people with colorectal cancer (CRC) develop metastatic disease, meaning the cancer becomes advanced because it spreads from the colon to other places in the body, often to the liver or brain. While there are numerous ways to treat metastatic CRC, little is known about how to predict which treatment will work best for each patient. That lack of knowledge contributes to the low 5-year survival rate of 14% for this advanced type of CRC.
In order to develop more effective treatments, researchers need to better understand what drives CRC metastasis—how the original colorectal cancer (primary tumor) spreads. One thing they’re searching for are biological predictors (known as biomarkers) for metastasis.
The Research: Christopher Maher, PhD, and his lab team are looking for such biomarkers by studying molecules called long non-coding RNAs (lncRNAs). His lab collaborated with another ACS grantee, Ryan Fields, MD, who also works at Washington University School of Medicine.
In colorectal cancer, IncRNAs have been shown to promote a tumor’s progression. Maher’s team recently published a study about the identification of a specific lncRNA in a CRC primary tumor that shows changes in metastatic tumors. This lncRNA is called RAMS11 (RAMS stands for RNAs Associated with MetastasiS).
They found RAMS11 at high levels in both primary CRC tumors and metastasized tumors, meaning it can possibly be used as a biomarker in certain cases to help diagnose metastatic CRC. This knowledge may help cancer doctors move from a one-size-fits-all treatment approach to a personalized and precision-based approach. It will help them more reliably predict which patients have the highest risk for developing metastatic cancer while allowing them to spare lower-risk patients from aggressive treatments.
Maher’s team also showed that RAMS11 triggers some tumors to metastasize and become resistant to some chemotherapy drugs.
Why it Matters: Maher’s identification of RAMS11 as a potential biomarker for CRC tumors that have metastasized is the first step toward the development of a new drug that could target RAMS11 to treat aggressive, metastatic forms of colorectal cancer.
Maher’s and Field’s work may also have a broader impact: they found high levels of RAMS11 in tumors for other types of cancer, and the chemotherapy drug they studied is also used for other cancer types.