Colorectal cancer (CRC) is one of the deadliest cancers worldwide, and one of the biggest challenges in treating it is therapy resistance.
Many patients undergo chemotherapy, but in some cases, cancer cells find a way to survive and keep growing.
Now, researchers at The Tisch Cancer Institute at Mount Sinai have discovered a key reason why this happens.
A study published in Nature Genetics reveals that some colorectal cancer cells can revert to a fetal-like state, allowing them to escape chemotherapy. This process, called oncofetal reprogramming, helps the cancer become more adaptable and resistant to treatment.
How Cancer Cells Change to Survive
For years, scientists believed that colorectal cancer was mainly driven by a specific type of cancerous stem cell known as LGR5+ cancer stem cells. Many treatments have tried to target these cells, but the results have been disappointing.
Now, Mount Sinai researchers have found that some LGR5+ cells don’t just die under treatment—they transform into a different state, similar to fetal cells. This change makes them more flexible and resistant to chemotherapy, allowing them to continue growing and spreading.
“This discovery challenges the conventional belief that colorectal cancer is driven by a single, uniform cancer stem cell population,” said Dr. Slim Mzoughi, the study’s lead author and an assistant professor at Icahn School of Medicine at Mount Sinai. “Instead, we found that multiple distinct cancer stem cell states exist, and they work together to help the tumor survive.”
A New Way to Fight Therapy Resistance
The study not only explains why some colorectal cancers resist treatment, but also offers a potential solution. Researchers found that by blocking the oncofetal program, they could make cancer cells more vulnerable to chemotherapy.
Dr. Ernesto Guccione, a co-investigator and professor at Mount Sinai, emphasized that this discovery could lead to new treatment strategies. “Our data suggest that combining inhibitors of the oncofetal program with current treatments could significantly improve survival for CRC patients,” he said.
What’s Next?
Scientists are now working on developing new drugs or repurposing existing FDA-approved drugs to specifically target the oncofetal program. If successful, this approach could:
- Make chemotherapy more effective by preventing cancer cells from becoming resistant.
- Reduce recurrence by eliminating the cells that cause the tumor to grow back.
- Improve survival rates for colorectal cancer patients.
This research provides a major breakthrough in understanding why some colorectal cancers refuse to respond to treatment. With further development, these findings could lead to more effective therapies and offer new hope to CRC patients around the world.
If you care about cancer, please read studies that a low-carb diet could increase overall cancer risk, and vitamin D supplements could strongly reduce cancer death.
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The research findings can be found in Nature Genetics.
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