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Article: Controlling cancer rather than killing it

by JimNY on Tue Sep 09, 2014 1:49 pm

I came across this article this afternoon and thought many people here might find it interesting. It's from the New Yorker magazine, and it discusses techniques to treat people with cancer that focus on transforming cancer cells, or otherwise controlling them, rather than killing cancer cells.

Here's a link to the article:

Jerome Groopman, "The Transformation: Is it possible to control cancer without killing it?", The New Yorker, September 15, 2014.

It's a LONG article, but it's written by a physician, so it has some particularly interesting insights. Here are a few quotes that give a flavor of the things discussed in the article:

In discussing AG-221, a drug being developed by Agios to treat acute myeloid leukemia (AML),

The breakthrough is notable in part for the unconventional manner in which the drug attacks its target. There are many kinds of cancer, but treatments have typically combatted them in one way only: by attempting to destroy the cancerous cells. Surgery aims to remove the entire growth from the body; chemotherapy drugs are toxic to the cancer cells; radiation generates toxic molecules that break up the cancer cells’ DNA and proteins, causing their demise. A more recent approach, immunotherapy, coöpts the body’s immune system into attacking and eradicating the tumor.

The Agios drug, instead of killing the leukemic cells -- immature blood cells gone haywire --coaxes them into maturing into functioning blood cells. Cancerous cells traditionally have been viewed as a lost cause, fit only for destruction. The emerging research on AML suggests that at least some cancer cells might be redeemable: they still carry their original programming and can be pressed back onto a pathway to health.

In a discussion of how bone marrow samples look under the microscope, as it relates to studies being done of another Agios drug,

That afternoon, I examined microscope images of the bone marrow of a patient who had not been treated with the drug. As a hematologist, I often dread taking in this view. Up close, healthy marrow looks like an Impressionist painting -- a variegated landscape of cell types and colors. Leukemic marrow is a monotonous canvas of cancer cells; the images I was looking at showed hardly any normal blood cells being made. Then I examined images from a patient who had received the Agios drug. Typically, when a patient with AML is treated with high doses of chemotherapy, the marrow is emptied of all living cells; what’s left is a moonscape of fat globules and fibrous tissue. The images at Agios showed robust marrow: the leukemic cells had been forced to mature and had reverted to functioning white blood cells, red blood cells, and platelets. They were transformed.

On cancer cells in general:

In medical school, we were taught that although cancer comes in many forms, it has one immutable characteristic: it is composed of immature cells. The research on these blood cancers, however, suggests that this trait may be reversible after all, and that the cancer cells, when prompted to mature, become susceptible to therapies to which they would otherwise remain resistant.

On the concept of "cancer stem cells":

“I understand full well the attractiveness and the seduction of the cancer-stem-cell model,” William Kaelin, a cancer biologist at Harvard’s Dana-Farber Cancer Institute, told me. “But so far it hasn’t made any predictions that I wouldn’t have otherwise made. I think we already knew that cancers tended to coöpt stem-cell pathways that are important for normal stem cells. And I think we already knew that many genes that are involved with stem-cell biology were occasionally mutated in cancers.”

As I said, it's a long read, and it's also not directly related to myeloma. But there's some interesting stuff there.

JimNY

Re: Article: Controlling cancer rather than killing it

by Eric Hofacket on Tue Sep 09, 2014 2:53 pm

Very interesting approach to cancer treatment -- one that I hope sees more success. I am all for whatever works, conventional chemo and surgery, novel agents, this emerging approach, or even things people call “alternative medicine,” if there is science based evidence it works.

The link is not working for me on my work computer so I cannot read it now and will have to try it at home. I have seen some other publishing’s related to this topic before.

“The Agios drug, instead of killing the leukemic cells -- immature blood cells gone haywire --coaxes them into maturing into functioning blood cells. Cancerous cells traditionally have been viewed as a lost cause, fit only for destruction. The emerging research on A.M.L. suggests that at least some cancer cells might be redeemable: they still carry their original programming and can be pressed back onto a pathway to health.”

A question in my mind is what does that mean to “[coax] them into maturing into function blood cells”.

I understand there are several core characteristics and behaviors of cancer cells that define them. One of these is that cancer cells are immortal and never die. Does the Agios drug reverse the cells back to being mortal again with limited number of divisions that can occur before cell death occurs? That would be significant.

But another is that cancer cells metastasize to other regions of the body where they should not be found and take root. Another is cells that normally do not form solid tissue masses, like plasma cells, do.

Does the Agios drug reverse these cell characteristics too?

It would be remarkable to find a drug that reverses the cancer characteristics and reverts cells to normal functioning non-cancer cells and, for some types of cancers, maybe this is a possibility. But from my readings with myeloma and the large number of genetic defects that are found in plasma cancer cells -- deletions, translocations, including some that are seemingly major such as extra chromosomes, that lead to all these cancer traits -- I am having trouble seeing how a drug is going to coax a cancerous plasma cell to correct all these defines and go back to being a normal cell.

In my readings I see there is some natural ability for a cell to repair DNA damage, but there comes a point where, if that damage is too significant to be repaired, the normal response for the body is to program cell death for the defective cell, which does not happen with cancer cells and is another one of their core characteristics.

If the body cannot repair these cells naturally on their own, it would be remarkable if the Agios drug can make that happen given the complexity of the task.

Eric Hofacket
Name: Eric H
When were you/they diagnosed?: 01 April 2011
Age at diagnosis: 44

Re: Article: Controlling cancer rather than killing it

by Mijji on Fri Sep 12, 2014 11:54 am

This is a fascinating line of research and, although so far it is related to leukaemia, I hope that there is a sister drug that will be found to have similar effects for myeloma.

Does anyone know more about this?

Another inspiring development is the use of anti-angiogenic drugs for cancer. Although this is primarily related to tumour-type cancers, one of the effects of Revlimid is anti-angiogenic, so it would be interesting to know what relevance anti-angtiogenics have to myeloma.

With time it could be that medication will be developed that sustains the body's autoimmune response to myeloma with fewer and lesser undesirable effects.

Mijji
When were you/they diagnosed?: 2011


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