A new study from researchers at Mount Sinai’s Tisch Cancer Institute, published in Nature Genetics, has uncovered a surprising reason why some colon cancers are hard to treat. Scientists found that certain colon cancer cells can switch back to a fetal-like state, helping them survive even when attacked by strong chemotherapy drugs.This process is called oncofetal reprogramming, and it gives cancer cells a dangerous advantage: they become more flexible, harder to destroy, and more likely to keep growing. This discovery helps explain why some colon cancers come back even after treatment and gives doctors new ideas on how to fight back.
What is oncofetal reprogramming in colon cancer
Oncofetal reprogramming means some cancer stem cells—specifically LGR5+ cells, change their identity and behave more like fetal (early developmental) cells. These “reprogrammed” cells are not mature like normal colon cells. Instead, they go back to a more primitive, less specialized form.Why is this important? Because fetal-like cells grow quickly, adapt easily, and are very resistant to damage. They can hide from treatments designed to kill normal cancer cells. So even if chemotherapy kills most of the tumor, these reprogrammed cells can survive, multiply, and cause the cancer to return.This makes oncofetal reprogramming a key reason why colon cancer can resist treatment and keep coming back.
Why this finding matters for the treatment of colon cancer
Understanding how oncofetal reprogramming works can lead to better treatment strategies for colon cancer. Right now, most cancer treatments are designed to target the “normal” cancer cells. But they may miss the reprogrammed, fetal-like cells, which are stronger and more resistant.The new research suggests that the best approach might be to combine chemotherapy with drugs that stop oncofetal reprogramming. By doing this, doctors could target both the mature cancer cells and the hidden, more dangerous ones, making it harder for the cancer to return.This combined treatment strategy could lead to better long-term results and reduce the risk of relapse in people with colon cancer.
How do these cancer cells resist chemotherapy
Cancer stem cells, especially those that undergo oncofetal reprogramming, have special powers that help them survive even the most aggressive treatments. Here’s how:
- They can quickly remove drugs from their system by pumping them out, reducing the effect of chemotherapy.
- They are better at repairing DNA damage, so even if chemo harms them, they fix themselves fast.
- They avoid apoptosis (cell death), which is how many treatments try to kill cancer cells.
These traits make reprogrammed cancer cells highly resistant, and they often become the seeds of tumor regrowth after treatment ends. That’s why targeting only the regular cancer cells is often not enough.
What’s next in colon cancer treatment
The discovery of oncofetal reprogramming opens up new directions in cancer research. Scientists are now looking into targeted therapies that can block the signals or genes that allow this reprogramming to happen in the first place.If researchers can develop drugs to prevent cancer cells from shifting into this fetal-like state, it could make treatments like chemotherapy much more effective, and reduce the chance of the cancer returning.Clinical trials and further research will be needed, but this finding is a major step forward in understanding and treating chemotherapy-resistant colon cancer.Also read | 5 key reasons colon cancer is rising among young people; and ways to prevent
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