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Old 03-11-2012, 05:01 PM   #1
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Tumors can be more complex than imagined earlier: Study

Researchers speculate that cancers may be more complex that they knew. And that's why a single tissue sample taken from a single tumor may not be the best way to figure out a course of treatment they claim.

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Old 03-12-2012, 01:12 PM   #2
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Intratumor Heterogeneity and Branched Evolution

This "intratumor heterogeneity" issue is not a new revelation to cell function assaysts. As you can see, searching for these genetic predispositions, it is like searching for a needle in a haystack. One can chase all the mutations they want, because if you miss just one, it may be the one that gets through. Or you can look for the drugs that are "sensitive" to killing all of your cancer cells, not theoretical candidates.

Contrary to anlayte-based genomic and proteomic methodologies that yield static measures of gene or protein expression, functional profiling provides a window on the complexity of cellular biology in real-time, gauging tumor cell response to chemotherapies in a laboratory platform. By examining drug induced cell death, functional analyses measure the cumulative result of all of a cell's mechanisms of resistance and response acting in concert. Thus, functional profiling most closely approximates the cancer phenotype.

Testing of one sample of the tumor may well not render an accurate environment, unless you are recognizing the interplay between cells, stroma, vascular elements, cytokines, macrophages, lymphocytes and other environmental factors. The human tumor primary culture microspheroid contains all of these elements. Studying cancer response to drugs within this microenvironment would provide clinically relevant predictions to cancer patients. It is the capacity to study human tumor microenvironments that distinguishes it from other platforms in the field.

They have observed some degree of "genetic drift" where mets tend to be somewhat more resistant to drugs than primaries. Over the years, they have often encouraged physicians to provide nodal, pleural or distant site biopsies to give the "best shot" at the "most defended" of the tumor elements when metastatic disease is found.

The tumor of origin (as in the NEJM study as well) and the associated mets tend to retain consanguinity. That is, the carcinogenic processes that underlie the two populations are related. This is the reason they do not see "mixed responses" (one place in the body getting better and another place in the body getting worse), but instead, generally see response or non-responses.

Heterogeneity likely underlies the recurrences that are seen in almost all patients. This is why they try to re-biopsy and re-evaluate when recurrences are observed. Heterogeneity remains a theoretical issue no matter what platform one uses. Why complicate this fact by using a less biologically relevant method like genomics that only scratches the surface of the tumor biology?

http://robertanagourney.wordpress.co...omic-analysis/
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Old 03-15-2012, 01:50 PM   #3
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Personalized genetic medicine: a bump in the road?

The latest British study on Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing may hinder personalized medicine strategies that depend on results from single tumor biopsy samples.

A reply to a Dr. Robert Nagourney blog posting about this study, brought up the Oncotype DX assay. The woman's breast tumor was early stage 1/grade 1 NO ER/PR positive Her2 negative and her Oncotype DX showed 8% recurrence rate.

After reading her pathology report, three years ago, she raised the question as to why the whole tumor was not looked at after the lumpectomy to make sure the diangosis was the same throughout the tumor. She was told it would be to lengthy, costly and she had nothing to worry about. She was told that they only test a slice of the tumor and throw the rest away. She was taken back by the oncologist's comment. Indeed, so would I.

After she read an article on the British study, is she to assume she may have been right? Or was the pathologist correct in telling her with his assessment of her tumor coupled with the Oncotype DX that things looked good for her and she was not on the Titanic. She was very depressed for someone who was three years out and wondering whether or not the treatment she received was really what she needed.

Indeed, intratumor heterogeneity can lead to underestimation of the tumor genomic landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized medicine and genetic biomarker development. Intratumor heterogeneity, associated with heterogeneous protein function, may foster tumor adaptation and therapeutic failure.

The study is significant because it suggests relying on one sample could overlook important genetic biomarkers that help make tailored treatments effective, explaining perhaps why personalized cancer therapy has been less successful than expected. This does refer to genetic testing and not to functional profiling.

Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

http://cancerfocus.org/forum/showthread.php?t=3640

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Old 03-18-2012, 10:41 PM   #4
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Re: Tumors can be more complex than imagined earlier: Study

Yeah...perhaps typical inability to biopsy multiple locations points to finding a circulating tumor cell tech that can inventory at a more systemic level.
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Old 03-23-2012, 09:12 PM   #5
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Re: Tumors can be more complex than imagined earlier: Study

How do you aggregate a sufficient number of cancer cells to make accurate determinations? Detectable tumor cells in the peripheral blood are present only in extremely small numbers. This precludes allowing a sufficient number of cells to incubate for a few days in the presence of chemotherapeutic agents. Analysis of a relatively small number of isolated cancer cells cannot yield the same quality information as subjecting living cells to chemotherapeutic agents, begging the question of whether or not it can accurately predict which drugs will work and which will not.
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