Chapter 08: The Largest Sarcoma Tissue Bank in the World
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Description
In an important collaboration, Drs. Pollock and Yu created what would become the largest sarcoma tissue bank in the world, with fifty different cell lines and twenty-five animal models for studying the disease. In this Chapter, Dr. Pollock sketches the value of understanding the molecules the drive nearly 100 sarcoma subtypes and notes the possibility for therapy that come from this research. (He gives an example of how understanding molecular processes in the tumor can lead to physicians to reduce chemotherapy in sarcoma patients, and notes that the Bank has collaborations with several industrial concerns. The research group is made up of about twenty faculty, fellows, and students from the Graduate School of Biomedical Sciences who focus on investigating the basic biology of sarcoma. He underscores the need for such groups, as sarcoma is underfunded even in relation to its incidence in the population and understanding how it works can contribute greatly to the understanding of cancer in general.
Identifier
PollokRE_02_20121010-C08
Publication Date
10-10-2012
Publisher
The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center
City
Houston, Texas
Interview Session
Raphael Pollock, MD, Oral History Interview, October 10, 2012
Topics Covered
The University of Texas MD Anderson Cancer Center - Building the InstitutionThe Researcher Professional Practice The Professional at Work Collaborations Overview Definitions, Explanations, Translations Understanding Cancer, the History of Science, Cancer Research Discovery and Success Multi-disciplinary Approaches Building/Transforming the Institution MD Anderson Impact Understanding Cancer, the History of Science, Cancer Research The History of Health Care, Patient Care
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Disciplines
History of Science, Technology, and Medicine | Oncology | Oral History
Transcript
Well, sure. We created a tissue bank that was derived from patients that I and my colleague operated on, which is now the largest sarcoma tissue bank in the world. And from that we were able to create a number of cell lines as well as small-animal models of transplanting sarcoma from patients into immunocompromised animals and then being able to see how metastases took place and developing different types of manipulations that one might use in those types of models. So it took us closer to therapeutic applications than what I had been able to examine at an earlier point.
Tacey Ann Rosolowski, PhD:
Could you give me an example of how one of these came close to therapeutic implications?
Raphael Pollock, MD:
Well, by understanding the unique molecules that drive specific sarcoma subtypes—and there’s more than at least fifty and maybe as many as 100 different distinct sarcoma subtypes, and each has their own unique biology—so by understanding the unique molecules driving the biology underlying each of these specific subtypes, you come closer and closer to an application that may be useful in patients. So there is a broad class of drugs, for example, that we’re studying now called HDAC inhibitors, and these are important drugs from the point of view that how proteins are manufactured are under control of the substances that these drugs can inhibit. So in inhibiting the production of certain proteins, it enables you to get equivalent tumor control with much smaller doses of traditional chemotherapy and therefore much less toxicity. So these types of combinatorial approaches are the way that we’re thinking about trying to develop new therapies for sarcoma. But the reality is we have, oh, probably at this point about twenty animal models and fifty different cell lines, all of which are being used to fuel collaborations throughout the world, and a number of pre-clinical drug discovery applications working with industrial concerns outside of Anderson. So it’s become a much larger enterprise. Currently we have approximately twenty people in the research group. That includes pre-doctoral students at the Graduate School of Biological Sciences, postdoctoral fellows, clinician investigators, including faculty from five different departments, so it’s a very large group of people. And much of what we’re focusing on is actually discovery of basic biology—why certain subtypes of sarcoma behave in certain ways. We’re trying to learn more about the genes that may be ultimately controlling the production of proteins that drive these types of aberrant behaviors.
Tacey Ann Rosolowski, PhD:
Is this project in any way linked to that work you were describing to me the other day where you were quite involved with a multi-institution collaboration to start defining the staging of sarcoma?
Raphael Pollock, MD:
No, that’s a whole totally different process.
Tacey Ann Rosolowski, PhD:
Yeah, I’m just sort of investigating the sort of basic nature of these different types of sarcomas. It seemed a little bit linked, but I understand.
Raphael Pollock, MD:
Although, in an indirect way it is linked in that we’re very optimistic that some of these molecular factors that we are identifying in the laboratory will ultimately be useful as biomarkers for disease—perhaps as therapeutic targets. But as biomarkers, they may be pertinent to describing the stage of the tumor, and so the idea of developing these as molecular staging characteristics will ultimately, I think, prove possible with sarcoma, as is already being done in other disease, like melanoma and breast.
Tacey Ann Rosolowski, PhD:
So it’s possible to have— It’s possible to visualize a test that would tell you what stage it was at, or would there be another kind of—?
Raphael Pollock, MD:
Well, perhaps a test or at least an identifiable factor that would give you a more refined understanding about a prognosis and may, in turn, inform therapeutic decisions. So those would be the types of things that we would expect this knowledge to be able to be applied in a practical fashion. In a disease that is exceedingly rare, for which there are very few research resources available, as compared to more common cancers.
Tacey Ann Rosolowski, PhD:
Yeah, I was going to ask you about that yesterday—if it was difficult because of the rarity of the disease to get funding.
Raphael Pollock, MD:
It certainly is underfunded relative even to its rare incidence, but I think that the problem is compounded by the fact that, given that it is rare, it means that most institutions will not have sufficient patient tumor tissue resources to actually undergird a research program. And that being the case, it’s hard to attract young people, particularly clinician investigators or pre-doctoral PhD students, to study these diseases, because in some ways these, as rare or orphan illnesses, are not going to receive the same type of attention.
Tacey Ann Rosolowski, PhD:
Yeah, so it’s a—
Raphael Pollock, MD:
So it becomes a vicious cycle.
Tacey Ann Rosolowski, PhD:
Exactly. Is there something—?
Raphael Pollock, MD:
But on the other hand, almost anything that you learn is going to be publishable because it’s novel information that has not been discovered or reported out yet.
Tacey Ann Rosolowski, PhD:
And I was going to ask, too; is there something about studying sarcoma that could allow you to learn more about cancer in general?
Raphael Pollock, MD:
Absolutely. As a matter of fact, sarcoma has been a very powerful level in that regard. There are 3 aspects: This is the first disease in which the use of neoadjuvant chemotherapy before surgery was attempted. This is the first disease in which genuine outcome prospective randomized clinical trials to define the differences or equivalents of outcome in organ and limb-sparing approaches, as compared to more radical surgical approaches, was done. And this is the first disease system in which personalized therapeutics were ever developed. So here are three key themes in contemporary oncology, all of which ultimately emanated from individual investigations in this very, very rare form of cancer.
Tacey Ann Rosolowski, PhD:
Do you have—? What is your view of why that’s the case?
Raphael Pollock, MD:
Each of these discoveries in some ways was somewhat serendipitous. The use of neoadjuvant chemotherapy, for example, was first demonstrated by pediatric oncologists at Sloan-Kettering in the early 1960s, when a decision was made to no longer treat pediatric osteosarcoma with radical amputation up front and instead try to do limb-sparing surgery, which would require the production of prostheses—metal, shaped replacements for bone, because osteosarcoma is a sarcoma of bone. And the problem at the time was that extruding these custom-made prostheses was a twelve-to-eighteen-week proposition. They had to be manufactured in Switzerland and then imported. So it was perceived by Gerald Rosen and others that instead of just waiting for eighteen weeks, at which time the tumor could spread, that they should do something, like use chemotherapy to try to control it—what, at the time, was a radical departure. And, lo and behold, they were able to observe that the patients who received chemotherapy while waiting for their prosthesis to show up ultimately had lower rates of metastasis. And from that, the entire neoadjuvant was extrapolated.
Recommended Citation
Pollock, Raphael E. MD and Rosolowski, Tacey A. PhD, "Chapter 08: The Largest Sarcoma Tissue Bank in the World" (2012). Interview Chapters. 1320.
https://openworks.mdanderson.org/mchv_interviewchapters/1320
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