Chapter 07: Bold Research: Opening the Field of Personalized Therapy

Chapter 07: Bold Research: Opening the Field of Personalized Therapy

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[Note: At the beginning of this Chapter Dr. Hong refers to “my file”: this is a PowerPoint presentation that is available as a supplement to this interview.]

In response to a question about his strategy of asking “bold” research questions, Dr. Hong speaks in detail about his third area of bold research –personalized, targeted therapy. He defines personalized therapy and returns to a discussion of the BATTLE trials discussed in Chapter 7 (Biomarker Based Approaches of Targeted Therapy for Lung Cancer Elimination Project). Dr. Hong describes the trials’ central hypothesis: by acquiring genetic information about a tumor, one can identify what drives the cancer and then hijack it, therefore blocking cancer. He notes that colleagues were very skeptical when he developed the study, but the published results opened up the new field of personalized therapy at an institutional, national, and global level. Dr. Hong notes that he takes a lot of pride in taking this approach from an idea to a force that galvanized an entire field. He believes that this approach can make an impact on cancer science and treatment of cancer at all stages of the disease.

Dr. Hong then notes that as the Institute for Personalized Therapy was being founded, the results of the BATTLE trial gave confirmation that the approach was sound. Dr. Hong explains that personalized therapy requires a different paradigm of treatment and new research modalities based in genomic medicine and he then gives reasons why people were skeptical of the approach at first. He also notes that this approach is fundamentally multi-disciplinary and lists the disciplines that collaborate.

Dr. Hong next speaks briefly about team science –an approach essential to personalized, targeted therapy. He then lists his contributions to cancer science.

Identifier

HongWK_02_20131016_C07

Publication Date

10-16-2013

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; The Clinician; Discovery and Success; Overview; Definitions, Explanations, Translations; On Research and Researchers; The Administrator; Multi-disciplinary Approaches; Collaborations; The Professional at Work; Professional Practice; Obstacles, Challenges; Patients; Patients, Treatment, Survivors; Controversy

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:

Okay. I’ll just put the identifier on. I’m Tacey Ann Rosolowski, and today is October 16, 2013. The time is about three minutes after 2 o’clock. And I am on the 11th floor of the faculty center on the main campus of MD Anderson talking with Dr. Waun Ki Hong. This is our second interview session. And thank you for doing this today.

Waun Ki Hong, MD:

Again, thank you, Tacey—I think all of us are on such a busy schedule—for visiting my office to have some informal chatting on my research and my administrative role, et cetera.

Tacey Ann Rosolowski, PhD:

Well, I appreciate you giving me the time.

Waun Ki Hong, MD:

I think I touched upon the periphery last meeting on the area of organ preservation and also chemoprevention. I think you covered it quite extensively those two areas. You can see things in my file; it is easy to read there. And you can verify all the things that I talk about.

Tacey Ann Rosolowski, PhD:

Sure, and just for the recorder let me say that Dr. Hong is referring to a PowerPoint, which he has kindly agreed to share with the archive. And that will be available via the interview.

Waun Ki Hong, MD:

So the third area of so-called “very bold” research that I had the opportunity to implement was the so-called personalized targeted therapy. What that means is cancer is basically an alteration in the genetics—abnormal DNA proliferates a cell and becomes cancer. And then obviously there are genetic changes that are heterogeneous. And the genetic changes are heterogeneous and then become the cancer. That’s the difficult part. They’re so heterogeneous you cannot really pinpoint—

Tacey Ann Rosolowski, PhD:

You know—I hadn’t realized that until I talked to Dr. [John] Mendelsohn [Oral History Interview] and he began speaking about personalized therapy and targeted therapy. Now when it became clear that cancer was a moving target in this way, did that dramatically change your thinking and your approach?

Waun Ki Hong, MD:

In fact, my study, the so-called BATTLE trial on lung cancer, once successfully completed there was impetus of establishing an Institute of Personalized Cancer Therapy where Dr. [John] Mendelsohn is the director.

Tacey Ann Rosolowski, PhD:

I didn’t realize that.

Waun Ki Hong, MD:

I was the first director of IPCT. So let me tell you just a brief background. The idea is very simple, which is there is a tumor there, and you can do the biopsy. Then you can visualize changing of the genetic cord. Then, once the genetic changes took place, then the next thing is sending signals—signals to the cells to proliferate. The signaling pathways are extremely heterogeneous. And you can block the one signal, and that’s not good enough. But you have to understand—this is very important—that there is always a driver—a cancer driver gene. And the rest of the things are genetic changes. But many genetic changes can be just the passages. It’s not harmful. So the idea is that we do the biopsy, identify and visualize genetic changes, and then identify the cancer driver. Then we hijack the cancer driver by giving the right treatment. It’s a simple concept. So we basically developed a hypothesis, which was that cancer drivers can be identified through the biopsy materials, so then cancer drivers can be hijacked with specific drugs. So that’s the story. To answer the questions, we did a study called the BATTLE, which is biomarker-based approaches of targeted therapy for lung cancer elimination. That’s BATTLE. You can see the slide here.

Tacey Ann Rosolowski, PhD:

And that was actually funded by the Defense Department.

Waun Ki Hong, MD:

Yes.

Tacey Ann Rosolowski, PhD:

Okay. How did that happen?

Waun Ki Hong, MD:

I wrote up the grant and then competed for funding through the DOD. It was a substantial amount of funding, about $7 million. So we proved that we could do it. When I developed that study, everybody was skeptical. They said it would be impossible to do the biopsy, and, “There is no way that you can analyze the genetic changes through the comprehensive molecular analysis,” but we did in two weeks. And somehow we did that. Basically, once we completed the trial and we published a paper and presented to the opening primary plenary session [Hong: AACR 2001], it really galvanized the whole field and opened up the field of personalized targeted therapy. Initially, we studied lung cancer. Now, I think, that concept of biopsy and treatment at the biomarker innovated targeted therapy to hijack cancer drivers. So it opened up the whole field. Now it’s not only within institutions, but nationwide and worldwide that so-called BATTLE-like approaches have been developed and investigated. I take a great deal of pride about this BATTLE initiative and starting something from an idea, then proving it, then demonstrating it’s feasible, and galvanizing the whole field. So the bottom line is that whether this unique type of approach can make an impact, I think that remains to be seen. But I think we’re moving in that direction. I think definitely we will make an impact, because we now understand more and more about cancer genetics and genetic tissues. And a lot of new agents are coming out of the pipeline, and we can have opportunities to really identify the cancer drivers. Then, also, at the same time we have now more tools that we can really kill those cancer drivers. If they’re sold, I think they really would make an impact.

Tacey Ann Rosolowski, PhD:

What do you think is the next wave of research coming from or building on this opening up of the field?

Waun Ki Hong, MD:

Already this kind of trial is rapidly proliferating—increasing. Then eventually, that kind of approach can be applied in the treatment of all different stages of cancer, not only advanced stages, and also intermediate stages, and even the early stage after surgery. Not everybody can be cured. But once you do the surgery, then you will find those molecular cancer drivers. Then based on drivers, you can give the right agent to kill the drivers. In the past, we used to give the agent empirically, like shooting in the dark. That strategy didn’t work that well. So this is a more personalized, pinpointed and targeted bullet. That’s the bottom line.

Tacey Ann Rosolowski, PhD:

Now you said that this research—the research that came immediately out of the first BATTLE trial—resulted in the founding of the Institute for Personalized Therapy here at MD Anderson.

Waun Ki Hong, MD:

When I was doing that trial everybody was so skeptical, but they were encouraging. Then the institution was about to turn to develop this institute in targeted therapy, so completion of the BATTLE trial reassured the confidence of the institution to establish that IPCT. Do you understand what I’m saying?

Tacey Ann Rosolowski, PhD:

Yes.

Waun Ki Hong, MD:

So if that trial was a failure, obviously, people would be discouraged. Then they would lose their confidence, and the institution would be down.

Tacey Ann Rosolowski, PhD:

What connection do you have now with the Institute of Personalized Therapy?

Waun Ki Hong, MD:

I closely interact. In fact, when I was in Cancer Medicine, we had more than fifty trials asking those kinds of questions.

Tacey Ann Rosolowski, PhD:

When I talked to Dr. Mendelsohn, he was speaking about the real importance of just collecting so many tissue samples—the kind of stock—for an encyclopedic knowledge of how cancer morphs. What are some challenges or requirements that you see in laying the groundwork for understanding the approach to cancer in this targeted way?

Waun Ki Hong, MD:

It’s changing the paradigm of cancer treatment. Traditionally, we just stick around with surgery, radiation, and chemotherapy. Now, I think, there is a new model to treatment, like a personalized cancer therapy, immunotherapy, based on the understanding of genomic medicine. Again, to accomplish that goal, then you have to obtain the tissues, and you have to store and preserve the DNA. Then a comprehensive genomic analysis can be done. Based on the discovery of the specific abnormal gene and abnormal pathway associated with cancer progression, then that can be hijacked with targeted therapy. It’s a beautiful concept.

Tacey Ann Rosolowski, PhD:

Why do you say it’s a beautiful concept?

Waun Ki Hong, MD:

The thing is, again, that that makes sense. Again, it was a concept that when I brought it up, it wasn’t that new. People thought about it. But I think I was the first one to do the BATTLE trial that demonstrated that it was biopsy driven—biopsy mandated, biomarker driven—and personalized cancer therapy can be done. So that’s important.

Tacey Ann Rosolowski, PhD:

Why were people so skeptical when you first proposed this?

Waun Ki Hong, MD:

Because of lack of experience, lack of confidence, lack of infrastructure. And it was also very expensive. If you’re too smart, you cannot be a good researcher. So if you have a good idea, you have to have some drive. I convinced the people, and it was multi-disciplinary teams—medical oncologists, surgeons, pathologists, interventional radiologists. It was about six or seven different disciplines in a collaborative effort. So it’s not easy to construct at all.

Tacey Ann Rosolowski, PhD:

How has the need for these interdisciplinary collaborations been a challenge? Because it sounds like research is increasingly multidisciplinary.

Waun Ki Hong, MD:

Yes, team science is the new word. This is not your science, this is not my science, this is our science. So executing that kind of BATTLE trial, you have to have a collaborative team effort. And that is challenging, because every individual is the same, and every individual is not the same—heterogeneous. So to put all of those people under one umbrella is a huge challenge. I think I was able to do that, because people trusted me and my leadership, and I was sharing credit with others. I was able to achieve that agenda effectively. A lot of people—there are a lot of good people, good scientists and good doctors, but if you don’t trust, then you cannot build up the morale, and then people schedule out. And they don’t work together. That’s doomed to failure.

Tacey Ann Rosolowski, PhD:

Do you find that younger scientists are educated with more of a mindset of collaboration than they were?

Waun Ki Hong, MD:

Yeah, that’s what I’ve been emphasizing and promoting more and more, that concept.

Tacey Ann Rosolowski, PhD:

I’m sure we’ll get to that when we talk about your administrative roles. Are there any other observations that you’d like to make right now about your research? Any other stories you’d like to tell?

Waun Ki Hong, MD:

I’d like to say this again. My studies are all on preservationperseverance, and that was a very bold trial. I felt like I made some significant contributions in that area. Second, in chemoprevention—that’s a very provocative concept and, I think, it’s the way to go. We have not really reached a point where people can practice, but we have the potential. And the third one is personalized cancer therapy through the BATTLE trial. I think that’s really opened up this field and has a tremendous potential to make an impact. And it’s so gratifying to see the incredible proliferation of BATTLE-like trials worldwide. That’s an important impact.

Tacey Ann Rosolowski, PhD:

Why do you think that’s so important? Waun Ki Hong, PhD That’s like you’re driving some science. And, ultimately, it’s connected to patient benefit. So that’s the bottom line. You’re doing something good. Yes, you can do it as individual faculty, you help some patients and you treat the patients, you cure the patients. That’s the most gratifying thing. And so things that I have done that really opened up the field and then let other people follow through, and then, ultimately, make some benefit for the patients. That’s the—I feel very gratified.

Tacey Ann Rosolowski, PhD:

Let me just pause the recorder real quickly.

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Chapter 07: Bold Research: Opening the Field of Personalized Therapy

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