Too Much MicroRNA Linked to Herceptin Resistance

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When cancer is resistant to a treatment it means the cancer cells aren't weakened or destroyed by the treatment any more. A study suggests that too much microRNA-21 (miRNA-21) in HER2-positive breast cancer cells is linked to Herceptin resistance. These results were reported at the 2010 American Association of Cancer Research annual meeting.

miRNA are small pieces of genes that can control how cells behave by making certain genes turn on and off. When there is too much of a certain gene or piece of gene, researchers call it "overexpression."

HER2-positive cancers make too much of the HER2 protein. The HER2 protein sits on the surface of cancer cells and receives signals that encourage breast cancer cells to grow and spread. About one out of every four breast cancers is HER2-positive. The targeted therapies Herceptin and Tykerb (chemical name: lapatinib) work by blocking the HER2 protein's ability to make HER2-positive breast cancers grow.

This study was done in a lab on cells, not in people. The researchers found that the PTEN gene wasn't as active when the cells had too much miRNA-21. The PTEN gene can help stop the growth of cancer cells. When miRNA-21 reduces the activity of the PTEN gene, cancer cells may grow more rapidly.

The researchers also found that exposing Herceptin-resistant, HER2-positive breast cancer cells that had too much miRNA-21 to molecules that lowered miRNA-21 levels made the cancer cells respond to Herceptin. While this research is very preliminary, the results suggest that lowering miRNA-21 levels might help treat breast cancer.

The researchers wanted to know if the lab results on too much miRNA-21 were linked to how breast cancer behaves in people. So they measured miRNA-21 levels in tumor samples from 37 women diagnosed with HER2-positive breast cancer treated with Herceptin:

  • 7 women had high miRNA-21 levels and 6 of them had the cancer grow while being treated with Herceptin
  • 30 women had low or medium miRNA-21 levels
    • 22 had the cancer shrink or remain stable while getting Herceptin
    • 8 had the cancer grow

So there seems to be a link between high miRNA-21 levels and poor response to Herceptin in women diagnosed with HER2-positive breast cancer, which agrees with the results in the lab.

Much more research is needed so doctors can understand how high miRNA-21 levels can help breast cancers grow, as well as how knowing miRNA-21 levels might help plan breast cancer treatment and if miRNA-21 could be a target for new breast cancer treatments.

Stay tuned to Breastcancer.org's Research News to learn about new results that might help doctors develop new breast cancer treatments and better use the treatments we have now.

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