Chapter 08: Brain Tumor Research: Translational Studies in Progress and the NCI Study Section

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Chapter 08: Brain Tumor Research: Translational Studies in Progress and the NCI Study Section

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In this chapter, Dr. Yung sketches his other research activities on glioblastoma. He first talks about his activities with the NCI and other groups focused on developing clinical, translational studies of brain cancer. He talks about the challenges of setting up such studies. Dr. Yung next talks about his clinical trials with the drug, BKM 120. He explains how this study also demonstrates the difficultly of attracting attention to a "small cancer" and how MD Anderson can partner with drug companies.

Identifier

YungWKA_02_20140507_C08

Publication Date

5-7-2014

Publisher

The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Interview Subject's Story - The Researcher; The Researcher; Overview; Definitions, Explanations, Translations; Activities Outside Institution; Understanding Cancer, the History of Science, Cancer Research; On Research and Researchers; On Pharmaceutical Companies and Industry; Industry Partnerships; Leadership; On Research and Researchers

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 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

Tacey Ann Rosolowski, PhD:

What are some of the other research projects that you worked on?

Wai-Kwan Alfred Yung, MD:

Well, besides the laboratory stuff, I --- I --- you know sort of --- I mean I said I am translational guy then I take --- I also, you know, led several teams in terms of developing clinical trials. Clinical research, you know, in the clinic, you know, in the clinic. So I was ver --- I was very involved in the --- in Ni --- NCI --- with NCI in st --- study section for research and then I was involved in the study section that is awarding clinical research, you know. And I was involved --- I was involved in our TOG designing clinical trials for brain tumor. I lead a consortium. You know, NCI developed a --- a --- in the mid ‘90s and late ‘90s NCI wanted to develop several groups of centers to do brain tumor research in a Phase 1 and Phase 2 setting. So I led one of those consortiums, put a field center together

Tacey Ann Rosolowski, PhD:

Hmm.

Wai-Kwan Alfred Yung, MD:

to develop clinical trials in the ea --- you know, early phase, clinical trial. Phase 1 and Phase 2 clinical trials studying new drugs. And that’s when we study these EGF receptor, inhibitors and new --- new drugs like temozolomide and other drugs.

Tacey Ann Rosolowski, PhD:

What were some of the challen ---

Wai-Kwan Alfred Yung, MD:

And then actually I led to --- led the big group of people doing st --- clinical trial on temozolomide that led to registration of temozolomide.

Tacey Ann Rosolowski, PhD:

Temozolomide

Wai-Kwan Alfred Yung, MD:

Yeah. T-E-M-O-Z-O-L-O-M-I-D-E and the trade name is Temodar, T-E-M-O-D-A-R.

Tacey Ann Rosolowski, PhD:

Hmm.

Wai-Kwan Alfred Yung, MD:

And that’s they’re approved --- the drug tests approve of TVM (4) in 1997.

Tacey Ann Rosolowski, PhD:

So it was the trials that you put together that confirmed the --- the usefulness of this drug.

Wai-Kwan Alfred Yung, MD:

___ ____ ___ (4) Yeah.

Tacey Ann Rosolowski, PhD:

Wow. I was going to ask you with your involvement of putting together these consortia, you know, working with different institutions, have there been some special or unique challenges that arose with setting up these translational projects?

Wai-Kwan Alfred Yung, MD:

In --- It --- It is always a challenge in trying to really get a group of, you know, highly intelligent, highly driven people together to march to the same drum or to move in the same direction. So that is always a challenge --- that’s a challenge. That is also a, you know, rate limiting factor for move --- for --- for advance. So, I mean, my observation in working with, you know, dif --- different consortium is that we really need to be able to enable and encourage, you know, people who are willing to work together and work together. I don’t think we can please everybody and I don’t think that we can force unwilling participants to participate in the same level. So --- So --- I --- I --- think the challenge for us really is for us to build a team with people willing to work together. And we al --- we --- we need to build teams with different focus.

Tacey Ann Rosolowski, PhD:

Uh-hmm.

Wai-Kwan Alfred Yung, MD:

You know, so that we can divide up the tasks into the multiple teams.

Tacey Ann Rosolowski, PhD:

Are you observing that younger generations of people are maybe more willing to work on teams than older generations? Is --- I mean is there any trend like that that you’re noticing?

Wai-Kwan Alfred Yung, MD:

Well I think the younger generation is more willing because I think the younger generation is, you know, is more cognizant of the interdependence of --- of --- the research arena that we are. I mean, we are --- in --- in --- in the --- in the --- in the new, you know, world of research is that --- is such a complex problem we’re faced with that if --- without working with each other with a larger --- larger group of people you cannot make anything happen.

Tacey Ann Rosolowski, PhD:

Uh-hmm.

Wai-Kwan Alfred Yung, MD:

As opposed to in the past when we’re just in the beginning, I can just focus on my own world and I really don’t need a whole lot of help to know how this protein works if I am smart enough to figure out some of the new techniques of doing it I can do it all myself. But now is a new --- the technology is so advanced. A lot of technology developed that one --- one group or one person is going to master the various areas and it’s just not possible. And also in terms of looking at a bigger picture of understanding how cells grow, understanding how cells move, understanding the --- the effect of the environment versus the effect of the cell itself. I mean the --- these are big questions. And it --- it really required a whole team of people to work together. And I think that realization brings people looking (5) So I think the team science is better recognized and --- and by nature you have to work in a team.

Tacey Ann Rosolowski, PhD:

Hmm. I --- in my background research I noted a couple of studies. And I don’t know if these are very significant --- significant enough to spend time on today. One of those, the Phase 2 study for BKM --- BKM 120 for patients with recurrent glioblastoma. That was part of the P13K pathway. Was that worth

Wai-Kwan Alfred Yung, MD:

Well, that, I mean

Tacey Ann Rosolowski, PhD:

talking about or ---

Wai-Kwan Alfred Yung, MD:

That --- that clinical trial is --- is pretty unique because, you know, that clinical trial is developed based on a lot of laboratory data that was generated in my lab as well as --- as with --- with --- with the company in Nevada who developed the drug BKM 120 and it also illustrates the difficulty for a small cancer like GBM, glioblastoma or for _____ other small cancer like thyroid cancers or sarcoma to get attention from Biotech or ____ (5) whose main goal is to really make sure they have a --- a drug that makes money.

Tacey Ann Rosolowski, PhD:

Right. Yep.

Wai-Kwan Alfred Yung, MD:

Right. So the pharmaceutical companies are really almost always focused on big cancer so that they --- they can have a big market.

Tacey Ann Rosolowski, PhD:

Uh-hmm.

Wai-Kwan Alfred Yung, MD:

Small cancer is --- never --- always ---, but you know, people --- you know --- they’re so --- so we work very hard to develop in the clinic --- the preclinical data and work with a company you know to get a drug in the lab to do some preclinical study and our lab is very interested in PTEN and PI3 kinase so --- so I established some relationship with --- with Nevada and was able to get some of their, you know, new drug early on to --- to --- work in the lab

Tacey Ann Rosolowski, PhD:

So

Wai-Kwan Alfred Yung, MD:

____ ___ (5) the PI3 kinase. So we develop those preclinical data for this drug BKM 120.

Tacey Ann Rosolowski, PhD:

So how did you convince then that it was worth their effort to do

Wai-Kwan Alfred Yung, MD:

Well we

Tacey Ann Rosolowski, PhD:

This study?

Wai-Kwan Alfred Yung, MD:

--- we generate the dat and lo --- and --- and --- and --- and we show them that this drug had a level --- a certain level activity in this --- in cell line that we generated as well as seeing mouse and --- and we worked with them, you know, work with the company, you know to compare data with their own in-house data snd, you know, then they would --- you know, after we have enough data generated we said okay so --- the --- the --- there is something there that we can we can --- we can take --- take a stab at this.

Tacey Ann Rosolowski, PhD:

Uh-hmm. So is ---

Wai-Kwan Alfred Yung, MD:

So we develop a f --- a clinical trial after they finish their Phase 1 all solid tumor trial knowing how much drug to use and then we develop a Phase 2 trial. But thi --- the --- we can only get that Phase 2 trial, you know, approved by them because we have pre-clinical data to convince them that it is a worthwhile attempt.

Tacey Ann Rosolowski, PhD:

Great. Yep.

Wai-Kwan Alfred Yung, MD:

You know --- you know.

Tacey Ann Rosolowski, PhD:

Yep. So is the assumption --- I mean I’m kind of thinking about your description of this in parallel with what you were saying earlier about the growth factor research that --- is Novartis and are you assuming that even though this is a small cancer what you will you will learn will have implications well beyond.

Wai-Kwan Alfred Yung, MD:

Definitely. I think, what you learn ---I th --- and this is one of the emphasis’ that actually Anderson, you know, is driving and can be --- is --- is to --- to tell the pharmaceutical industry that we have enough expertise here that we can partner with them early on in development of drugs for different cancer types used. You know, we can work with them early one to get the drug from them and utilize our laboratory and preclinical, you know expertise to generate the --- the --- what we call the pre-clinical data to --- to --- what work, what does not work and how it works and how it did not work. And --- and w --- with those knowledge we can, you know, have a m --- a --- a more careful way of designing the clinical trial and speed up the clinical trial development. I mean, this is exactly the --- the line of thinking that Dr. DePinho is, you know, is advancing, you know. And --- And I think for a small cancer like brain tumor it is even more important for us to really be able to have established relationship early, you know to --- to get those data because those data can be --- can be used to really convince the --- the --- the industry to say this drug may pay a little for this cancer and this cancer has a critical need for new drug.

Tacey Ann Rosolowski, PhD:

Uh-hmm.

Wai-Kwan Alfred Yung, MD:

And there may be a --- a small --- it’s just a --- it is a small investment that may have very important implications.

Tacey Ann Rosolowski, PhD:

Uh-hmm.

Wai-Kwan Alfred Yung, MD:

While you are investing in breast cancer well invest a little to brain tumor. There is --- you know.

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Chapter 08: Brain Tumor Research: Translational Studies in Progress and the NCI Study Section

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