Thursday, March 8, 2012

A Challenge for Personalized Medicine

Personalized medicine is the new Holy Grail of cancer therapy.  The drugs we currently use are stupid.  They don't actually target cancer cells, they target rapidly dividing cells.  Cancer cells divide rapidly, which is why chemotherapy works, but plenty of other cells in our bodies divide rapidly, and that is why chemotherapy causes so many side effects.

Not only that, but not every tumor of the same type responds similarly to the same chemotherapy.  For breast cancer, some tumors respond well to cyclophosphamide and doxorubicin, but others do not.

Cancer is, at its root, a genetic disease... meaning that changes in the genes within a cell cause it to transform from normal to cancer.  A lot of recent work has gone into identifying the specific mutations that lead to a particular tumor type, and using this information to gauge risk and make treatment decisions.

A by-product of this work has been the development of so-called targeted therapies... drugs that interfere with the abnormal function of a mutated enzyme, for example.  Because these drugs act only in cells that have that particular mutation, which presumably only happens in tumor cells, they are thought to be more specific and less prone to side effects.  The ultimate goal, then, of personalize cancer medicine would be to identify mutations in an individual's tumor and prescribe a regimen of targeted therapies that are specific for that tumor.  Not for the type of tumor... for the individual tumor.

An article in today's issue of the New England Journal of Medicine makes it clear that this approach is going to be more difficult than previously believed.

Most work aimed at identifying mutations in a specific tumor is based on a single biopsy of the tumor, the idea being that the important mutations will be present in every cell in the tumor.  Today's article addressed this issue directly by comparing the mutations found in multiple different biopsies from the same tumor.  What they found raises serious concerns.  Only about 1/3 of the mutations this group identified were present in every biopsy specimen from the same tumor.  The other 2/3 were found in only a subset of the biopsies.

At one level, this is not news.  Cancer scientists have been aware for years that tumors are heterogeneous... that is, not all of the cells are the same.  It stands to reason, then, that not every cell will have all of the mutations.  That there will be some cells with fewer mutations, and some with more.  And today's article does suggest that some mutations, probably the ones important for the original development of the tumor, are found throughout the mass.  However, if only a single biopsy is performed and used as the basis for making treatment decisions, most of the identified mutations will NOT be common throughout the tumor.

It's not the end of the world, but it does mean that developing and testing this kind of treatment approach is going to be a lot messier than people have previously believed.

Related Posts:

A Smarter War on Cancer
Is the Medical Community Complicit?
Genomic Medicine -- The Hope and The Hype


debwitter said...

Dear Doc,

No one is talking about ionizing radiation as the basic mutagen behind cancer. This history starts at the end of WWII. Actually earlier from Dr. H.J. Mueller who studied 40,000 generations of fruit flies to ascertain what was THE most mutagenic- chemical or radiation. He proved radiation in 1927.

Per government studies with bomb tests from 1950 - 1974 and using military staff as guinea pigs, all radioactive side effects are thoroughly known while at the same time thoroughly suppressed.

Just type in atomic bomb tests on google and you will see photos of bombs with thousands of military in close proximity to these tests. For further enlightenment there are several books such at Killing Our Own by Wasserman. That is the best but there are many others.

The sad fact of these bombs and power facilities is that they expose the population to energized particles which do not go away. They emit dangerous radiation for many, many years. Since this has been going on for over half a century the resultant current plague of cancer is now in full swing.

Most people will not accept truth on this subject due to effective lies surrounding this topic.

Thought you might be interested in this suppressed information and finding out the truth for yourself.


Unknown said...

I've been just starting to follow the idea of targeted therapy. I hope this doesn't sound geeky, but it's really cool that we're even be able to do it, even if we do have to take multiple biopsies.

I would venture to say that except in some geographical areas, the primary source of radiation which causes cancer is the sun. I've heard it said that if we did't die of old age, we'd all eventually get cancer. But the ironic thing is, for some cancers radiation is also the cure. Hopefully targeted therapies can stop the need for that, too.

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Keelytm said...

I didn't realize, before this blog, that the side effects of cancer treatments are caused because it targets all rapidly dividing cells. I think that personalized treatments are definitely the way to go. Are some targeted therapies already in use or on the market? Or is this still an emerging field? I want to talk to my Dad's cancer physicians about maybe changing his treatment, to see if there are targeted therapies for him.

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We'll cancer therapy is indeed not that 100% efficient. It is in fact far from perfect. Especially if the victim is not knowledgeable about its causes and what can further make it worst. Further studies such as this one is a stepping stone to improve the treatment regimen for cancer patients.

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Thank you for spelling this out! Our second home was a hospital for years as my son fought leukemia and then a gleosarcoma. I look forward to the day that no other parents lose their children to cancer.

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I wonder how this would be implemented in a large scale. The idea is cool but probably needs a lot of time to be developed for masses.

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Anonymous said...

I have had the opportunity to work on the breast cancer genome sequencing project going on in St. Louis and it has been amazing but initially disheartening. Like you mentioned, we have seen over 70 patients who were diagnosed with the same "type" of breast cancer but genetically they look like 70 different types. It is a lot of data to muddle through but this genetically targeted approach seems the logical next step based on what we're learning.

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Your ideas were interesting! I would like to agree that cancer cells usually divides really fast and chemotherapy is effective because of it's style. But I truly believe that alternative treatments to cancer are also effective depending on a cancer patient's body frame.

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