How Chemotherapy May Trigger Tumors’ Resistance

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Some 90% of cancer patients with metastatic breast, prostate, lung or colon cancers develop resistance to chemotherapy, and now scientists may have a clue as to why.

In a recent study published in the journal Nature Medicine, researchers report that an excess of a protein called WNT16B, which is produced by fibroblast cells near tumors, may spur cancer cells to grow and invade surrounding tissue.

What goes awry? Under normal conditions, fibroblast cells, which are the main component of connective tissue like tendons, work to heal wounds and produce collagen to maintain cells’ structure. But when fibroblasts are doused with chemotherapy, it damages their DNA causing them to overproduce WNT16B — up to 30 times as much of the protein as they should, a finding that the study’s authors called “completely unexpected.”

While WNT16B has been previously implicated in the development of normal cells and in some cancers, it hasn’t been identified as a source of treatment resistance until now.

The researchers, from Fred Hutchinson Cancer Research Center, characterized the protein as an unfriendly “neighbor” that lives in the same environment as cancer cells. “Cancer cells inside the body live in a very complex environment or neighborhood. Where the tumor cell resides and who its neighbors are influence its response and resistance to therapy,” said senior author Dr. Peter Nelson in a statement.

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Chemotherapy treatments are given in cycles in order to allow normal cells — and the patient — to recover from the toxic drugs. But the approach doesn’t always eradicate all tumors, allowing some to survive and evolve to become resistant to future rounds of treatment. “In the laboratory we can ‘cure’ most any cancer simply by giving very high doses of toxic therapies to cancer cells in a petri dish. However, in people, these high doses would not only kill the cancer cells but also normal cells and the host,” said Nelson.

The new research falls squarely in line with the idea that chemotherapy doesn’t just affect cancer cells, but also other cells, particularly those in and around tumors. “Sometimes this can be good — for instance, chemotherapy can stimulate surrounding healthy immune cells to attack tumors,” Fran Balkwill, a Cancer Research UK expert on the microenvironment of tumors, told BBC News. “But this work confirms that healthy cells surrounding the tumor can also help the tumor to become resistant to treatment.”

The researchers hope that by identifying the role of WNT16B, they can counter its effect and improve the effectiveness of chemotherapy.

“Cancer therapies are increasingly evolving to be very specific, targeting key molecular engines that drive the cancer rather than more generic vulnerabilities, such as damaging DNA,” said Nelson. “Our findings indicate that the tumor microenvironment also can influence the success or failure of these more precise therapies.

The findings are published in the August 5 issue of Nature Medicine.

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3 comments
hempangle
hempangle

I have a couple of people i work with that was diagnosed with certain cancers at one hospital,but they decided to get another opinion at two other hospitals and it looks like the first hospital lied to them,because the last to hospitals said they don't have cancer.I realise some people can't afford to get two or three opinions,but you have a good chance of dieing just from a lie.Now you see how some of these cancer wings stay open.I wonder where Dr Assad got his education.Is there a hidden cult involved in true greed.Human life means nothing i guess.What in the world is good about chemo and radiation.If they give you a year or less to live why do they give you twenty five treatments of chemo.And who is to say you have cancer in the first place.I here about people treating their own cancers with a different diet of enriched smoothies,or baking soda,and even hemp oil and are winning the battle with no side affects.Joanna Budwig cured people with cancer that were sent home to die and they got rid of her,but not until she cured a thousand or so people.She did it with flaxseed oil.Remember the Hoxey clinic?Their in Mexico and still in business.Rick Simpson from Canada was helping people cure their cancers until the US told Canada to put a stop to him.He cured or should i say helped people cure their own cancers.He had to move to another country.He is still getting patients from all over the world and he's not even a doctor and he is doing it with cannabis oil.Why do all the cures with no side affects get sanctioned and chemo and radiation still killing people.Is it the money?Greed vs life.Greed wins every time.