Published on Dec 15, 2020

Video Transcript

[MUSIC PLAYING] JOHN WHYTE: Welcome, everyone. You're watching Cancer in Context. I'm Dr. John Whyte, chief medical officer at WebMD. And today, I'm delighted to be joined by Dr. Elizabeth Jaffee. She's professor of oncology at Johns Hopkins University, as well as deputy director of the Sidney Kimmel Comprehensive Cancer Center. Dr. Jaffee, thanks for joining me.

ELIZABETH MARION JAFFEE: Thank you for inviting me, John.

JOHN WHYTE: Now, I also want to mention, you were a WebMD Health Hero a couple years ago. And in that ceremony, I want to read what you talked about. You talked about that you went into oncology because you wanted to give people hope but not cause them discomfort. That's pretty hard to do in cancer, isn't it?

ELIZABETH MARION JAFFEE: You know, I think it used to be hard to do. And I just remember when I was a first year fellow, I was taking care of patients, giving them chemotherapy. Half the time the chemotherapy might work for a few months and they'd feel sick during those few months. And I really felt there had to be a better way.

And that's why I went into research in immunotherapy. And immunotherapy doesn't have those sorts of symptoms. You don't get nausea. You don't vomit. You don't feel sick. You don't get any of those symptoms that you get with chemotherapy.

Now, I don't want to say it's not without its side effects. Certainly, we know that there are a different set of side effects, like autoimmunity. However, we can really pick those up early and control for it pretty quickly. The majority of patients, I think, feel really good during their immunotherapy treatment. And they're getting good results.

JOHN WHYTE: One of your areas of research is in vaccines. And when we talk about vaccines in cancer care, people are pretty surprised, because we're so used to vaccines as something we utilize before we get a disease rather than vaccines in cancer therapy really are for people that already have cancer. Can you explain that to our viewers so that they understand?

Because they're thinking vaccine? Well, what's happening with a vaccine? And we do kind of have these preventive ones, like HPV, and then these therapeutic ones. So if you don't mind, give us a little primer on vaccines.

ELIZABETH MARION JAFFEE: That's really an important question, too. I get a lot of people asking me that question. So ideally, I would love to have vaccines for cancers that are not virally associated. In the same way that we prevent something like cervical cancer, I'd love to prevent colon cancer or breast cancer.

But it's not as simple as a virus causing the disease. In fact, we know that there are now genes that make a patient susceptible to certain cancers. And that could account for as much as 30% or 40% of cancers. But typically, when we talk about vaccines and cancer, we are talking about patients who have cancer. And we're talking about trying to develop a way to activate the immune system, to alert the immune system to the existing cancer.

And we know certain proteins that the cancer cells express-- let's take a breast cancer cell-- that's different from a normal cell in the breast. And it's those proteins, just like a virus-- virus is protein, so does a cancer cell, making it different to the immune system from the normal cell. And so we're trying to take advantage of the type of vaccines that you would use to prevent a virus, but instead alert the immune system that the cancer is here now. Let's try to attack it with the same immune type cells that would attack a virus that has infected a cell.

The difference is that when you have cancer, once you are able to activate those immune cells, they might go into the cancer. But then they get stopped by those same proteins we call immune checkpoints, for which we have now treatments, the immune checkpoint inhibitors, such as the anti-PD-1 and the anti-CTLA-4. So in patients who don't respond to single agents, such as anti-PD-1 or anti-CTLA-4, it's because their immune system has never been alerted to the fact that there is a cancer.

So first we get a vaccine, alert the immune system, get the immune cells charged up. It's like an army of cells ready to go. They get stopped by the second type of protein, the immune checkpoints. We give an antibody to prevent that stoppage, that stop signal. And then the cancer cells can be killed by the immune cells.

JOHN WHYTE: And when we hear that, that all sounds so easy. And we do have a few vaccines that are approved by the FDA in terms of this therapeutic treatment regimen. But we don't have that many, Dr. Jaffee. But why do you think that is? We're talking about vaccine development, as you know, for COVID, which seems to be being done quickly. Why aren't we making more progress on vaccines for cancer?

ELIZABETH MARION JAFFEE: That is such a great question. So up until recently, it was very hard to tell what the different proteins were that made one patient's cancer different from its normal cells. And, in fact--

JOHN WHYTE: But don't cancer cells also, they exhibit some of the same proteins as normal cells do. So you have to--

ELIZABETH MARION JAFFEE: They do. Cancers do. And we do try to target those as well. But we're finding that it might be even more effective to target not only the ones that are shared, but also ones that are unique to a patient's given tumor.

And now that we can take a small biopsy, we can sequence all of the mutations that they have within a week or two, we can develop something called neoantigen-targeted vaccines. And those, we think, are going to be even more potent, because they're very patient-specific, than those that are targeting a shared antigen that may have been there for a long time. So these neoantigens, we think, are constantly changing and new ones are being made.

And so they may be-- the immune system may be less used to those particular proteins than the ones that have been there for a long time, such as a mutation, like mutated KRAS, which starts all of pancreatic cancers or starts many colon cancers. But your point is a really good one. Until we were able to also figure out that once you activate the immune system it could be quickly turned off by these other set of proteins, the immune checkpoints, we were giving vaccines and we were able to measure the immune cells, but we don't think they were able to do what they needed to do.

JOHN WHYTE: Now, you're an expert in pancreatic cancer. And we often hear about celebrities and pancreatic cancer-- Alex Trebek, Luciano Pavarotti, Steven Jobs, all with poor outcomes. Why is pancreatic cancer so hard to treat? It seems, if you're not following it, that we haven't made many advancements. But tell us what's going on with pancreatic cancer research.

ELIZABETH MARION JAFFEE: I really think that we are making some advancements. We certainly have better chemotherapies than we had even 10 years ago. So that's certainly an advance. It's not wonderful, but it's certainly an advance. It gives people some more time, and often quality time to be able to think about other new therapies they may want to try.

But it's a tough cancer, because by the time we detect it, unfortunately, it's pretty advanced. 70% of patients have advanced pancreatic cancer at the time of diagnosis. So we're just trying to control it. We're not really-- in most patients, the goal isn't to cure it at this point, because we don't have a curative treatment.

JOHN WHYTE: And you talked about the role of genes, especially as we're starting to think about therapies. And we talked to the CDC recently about the role of prevention and how much cancer is caused by lifestyle changes as opposed to inherited mutations or genetics. What's your thought process recently in terms of where we are in terms of the impact of lifestyle changes on certain types of cancers? It doesn't apply to everything. So can you help our listeners kind of think through how they can potentially play a role, either in helping to prevent cancer or helping to continue to prime their immune system if they do get impacted by a cancer diagnosis?

ELIZABETH MARION JAFFEE: Absolutely. Starting with evidence, we know for sure that cigarette smoking can cause many different cancers, not just lung cancer. So from the start, that's one lifestyle change you have to do. Making sure your children are vaccinated against the human papilloma virus and hepatitis B, and eventually we may be able to vaccinate against hepatitis C as well, but not yet. But these are causes of different cancers that we want to prevent our children, who eventually will become adults, from developing. So those are clear ones.

And then there are ones we can screen for and prevent metastasis, prevent dying from. And, obviously, your mammogram, you've got to get your mammogram, ladies. And you've got to get it regularly. Mammograms really detect early. Same thing with colonoscopy. Make sure-- and now the recommendations are even earlier, because--

JOHN WHYTE: I was going to ask you, so what--

ELIZABETH MARION JAFFEE: So colon cancer is becoming a younger person's disease in the 40s. So the recommendation--

JOHN WHYTE: Does that surprise you? Because we always thought of colon cancer, really, as a disease of aging. And that's what guide it when we started screening. And now we're seeing it in a younger population. And it's not the ones with inherited mutations that we're familiar with primarily.

So is it obesity? Is it red meat? What's your feeling on that?

ELIZABETH MARION JAFFEE: So I think the data is strong for red meat and for obesity, and obesity for breast cancer, obesity for colon cancer, certainly red meat, low-fiber diets. I mean, again, we don't have mechanism yet to tell us. Unlike cigarette smoking, I can give you some mechanism involved in the irritation of the lung tissue. But certainly, inflammation-- we know that inflammation changes in response to all of these things-- obesity, inflammation changes in response to fiber, red meat.

And so I think that diets that-- we call it the Mediterranean diet, diets-- healthy oils, fish oils, olive oils, vegetables, these are all really good diets to prevent cancer. And the data is epidemiologic right now, more what we call correlative, it correlates well with outcomes. But I suspect we will have mechanism in the next 10 years showing, for instance, inflammation being a major cause.

The other interesting area has been the microbiome. People have heard about this. We don't know yet exactly what about the microbiome. But again, this is environmental. There's something in our environment for sure that alters different people's microbiome. And food diet is a major part of that environment.

JOHN WHYTE: Aren't there some data that says that people who have cancer, the bacteria of their gut microbiome is different, whether that plays a role in cancer development or is after effect, are those-- do we expect to see more of that type of research?

ELIZABETH MARION JAFFEE: Yes, exactly right. There's a lot of work being done on trying to understand which of the bacteria in the gut are more susceptible or make you more susceptible for cancer. And, in fact, even responding to treatments, it's interesting that, particularly immunotherapy, we're starting to identify specific bacteria that may alter how you respond to therapy for cancer, particularly immunotherapy.

So we don't know a lot yet. We don't know which bacteria. But we're certainly-- there's a lot of research going on. And I think, again, in the next 10 years, we'll have a better sense of how to modify our gut bacteria. But again, I think diet is very important in the whole process.

JOHN WHYTE: And you mentioned that when you started your fellowship, treatment was changing. It's very different now. Where do you think it'll be 10 years from now? Take out your crystal ball.

What will you be working on? Will it still be vaccines? Will it be more preventive vaccines? Although those are, as you said, primarily viruses. What do you think it'll look like 10 years from now?

ELIZABETH MARION JAFFEE: Right, that's a great question. So I do believe we are in the era of precision oncology. So we're able to identify the genetics behind your cancer and identify drugs that can alter those genetics within the cancer or the proteins that are expressed due to the specific genetics. And so we no longer think of lung cancer as one cancer, but it's made up of five or six different types of genetics and different treatments based on what we assess when we sequence your cancer.

I think that the same thing with the immune system, not everyone's tumor responds in the same way as far as their immune system to the cancer. And so we need to understand how the immune system responds to pancreatic cancer versus a colon cancer versus a breast cancer. And we may have a set of drugs based on those differences.

I also think that we will be in an era of starting to think about not necessarily full prevention the way we prevent cervical cancer with the human papilloma virus vaccine, but something we call interception, where we screen people, we'll have screening tests detect early premalignancy and be able to figure out what the proteins are in the premalignancy that we could develop a vaccine for.

JOHN WHYTE: Premalignancy, people may not really be familiar with that term. So can you define it in a way that a non-clinician may think about it?

ELIZABETH MARION JAFFEE: Absolutely. When we take a biopsy of masses, sometimes they're not what we call a cancer because they're not going to metastasize. They're not invading the normal tissue. And they're not going to metastasize.

But they don't look normal. They have protein changes, early protein changes that tell us they're on their way to becoming a cancer. And so we call that a premalignancy.

JOHN WHYTE: We often see that in polyps in the colon, correct?

ELIZABETH MARION JAFFEE: That's a good example. Yes. Thank you.

JOHN WHYTE: Well, Dr. Jaffee, I want to thank you for providing your insights. You really do give people hope when you're talking about what we're seeing in terms of potential treatment options, as well as potential preventive therapies as well. So thank you for taking the time today.

ELIZABETH MARION JAFFEE: Delighted, and I wish everyone the best. Stay safe from COVID.

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