Published on February 18, 2021
New Therapies Target Multiple Myeloma's Biological Drivers
How exactly does a cancer cell grow? Why do those cells seem to take over so quickly? In this special edition of Answers Now, you will learn about the biological makeup of multiple myeloma cancer cells and how a new understanding of its genes, mutations, and proteins is allowing doctors to individually target cancer cells to keep them from multiplying.
Renowned multiple myeloma experts Dr. Nina Shah, MD, of UC San Francisco, Dr. Muhamed Baljevic, MD, of University of Nebraska and Dr. Sagar Lonial, MD, Emory University join Patient Power co-founder and two-time cancer survivor Andrew Schorr for an in-depth explanation of the new frontier of cancer treatment, targeting the biological driver of cancer. The doctors will discuss specific treatment developments including the clinical trial success of an XPO1 inhibitor that led to FDA approval in multiple myeloma. Watch now to learn how personalized medicine is creating therapies that are far better tolerated, and that allows for increased quality of life for myeloma patients.
This program is sponsored by Karyopharm Therapeutics. This organization has no editorial control, and Patient Power is solely responsible for program content.
Transcript | Answers Now: Understanding the Biology of Your Cancer
Andrew Schorr: Hello, and welcome to this special edition of answers now on Patient Power. I'm Andrew Schorr. And today we're meeting with three noted cancer experts and what we're going to discuss to help all of us understand—and I've been living with two cancers—is really, what is cancer? What fuels it? And what do we do about it today? Let's meet our three experts who are guests with us today. Starting in San Francisco, from UC San Francisco, UCSF, a noted myeloma specialist is Dr. Nina Shah. At the University of Nebraska is Dr. Muhamed Baljevic. And then down in Atlanta at the Winship Cancer Institute, is Dr. Sagar Lonial at Emory University there in Atlanta. Welcome to all of you. So Nina, let's just start this way. Any of us who were diagnosed with cancer, we're just careful, we're on the floor, and we really don't understand what cancer cells are versus other cells in our body. What makes cancer cells unique? What makes them bad guys?
How Do Cancer Cells Differ From Normal Cells?
Dr. Shah: Cancer cells are different because they like to grow unchecked. And when they do that, they take up the resources of other cells around them. So they're sort of a selfish type of cell. They don't have any stops, they don't have any rules, they just start growing out of proportion to others. And so then they just take up the space and the energy around them, and the nutrients around them. And that's what makes them bad.
Andrew Schorr: Okay. So in other words, with solid cancers that's what makes a tumor? Is it a clump of these bad guys?
Dr. Shah: Exactly right. So when people say they have a tumor or a malignant cancer tumor or malignancy, that's what it is. It's these cells that have become bad and unchecked and able to grow and grow so much that they now produce a tumor or a ball or some sort of nodule that can be seen. And that's what is causing this cancer.
Andrew Schorr: Okay. So in blood cancers, let's say that maybe start in your bone marrow, is it the same idea that there are cells that are normally healthy, that go awry and they can clog up your bone marrow or just operate improperly?
Dr. Shah: That's exactly right. So in the case of blood cancers, now you have cells that should be functioning normally in the bone marrow, and they should be becoming more mature cells and different cells. And instead, they just become the same cell over and over again. And they actually start to take up the space of the normal bone marrow, and they prevent the normal bone marrow from doing what it's supposed to do, which is produce your white cells which help fight infections, your red cells which give you energy and oxygen, and the platelets which help you make a clot.
Andrew Schorr: So in solid tumors, they may affect organ function. And in blood cancers, they may affect the blood cancer factory, and then your blood gets all out of whack.
Dr. Shah: Exactly.
Andrew Schorr: Did I get that right?
Dr. Shah: That's why a lot of... Right. So a lot of people come up with anemia or maybe low platelets or maybe a new infection because their white cells aren't working the way they're supposed to.
Andrew Schorr: Okay. Dr. Lonial. So let's go on and say, well, okay, how have we traditionally dealt with it? I mean, people hear about chemotherapy and they think of it as poisoning the cancer cells, but they know it affects healthy cells as well. How has chemotherapy traditionally attacked cancer?
How Does Chemotherapy Work? Is it Still Used to Treat Multiple Myeloma?
Dr. Lonial: Yeah, no. I think that's a really good question. And I think just one point to build on what Dr. Shah had mentioned earlier. And that is, the genetic abnormalities that often lead to transformation from a normal cell to a cancer cell occur actually probably at a higher frequency than any of us would care to acknowledge. But our immune system or the self-regulation within a cell is able to see that that's bad and kill it 99% of the time. It's that rare time that it figures out how to escape control of the normal immune system, that it really does become a problem, as Dr. Shah described.
Andrew Schorr: Let just comment on that for a second. I have this image, I used to live in the South, as you do. And so in the summer, you have the bugs flying around, and I don't know if they still have them but they used to have those bug zappers on the porch.
Dr. Lonial: Yep.
Andrew Schorr: And so in a way, our immune system, if I get it right is the bug zapper, but sometimes in this case, these cells get past it. They don't get zapped.
Dr. Lonial: Yeah. Correct.
Andrew Schorr: Okay. So getting to chemotherapy then, how have we traditionally, over many years, approached a lot of these cancers?
Dr. Lonial: Well, one of the hallmarks of cancer, certainly ones that cause symptoms, is that they tend to grow or proliferate faster than their neighboring cells. And so what most chemotherapy agents do is take advantage of the fact that you need normal division to occur, and they interfere with that division. So they prevent the cells that are dividing too fast from continuing to successfully divide. And that's why often the gut is a site of side effects, because the epithelium or lining of the gut also turns over relatively quickly in a normal fashion. And it's more sensitive to the side effects of chemotherapy that targets dividing cells. The same with the-
Andrew Schorr: Or losing your hair.
Dr. Lonial: Or losing your hair. That's correct.
Andrew Schorr: And let's just get to chemo-free for a second. The reason that that's of interest is a lot because of the side effects, right? Dr. Lonial, because you're often killing healthy cells, or you have these GI problems, hair problems, fatigue, a million different things, right?
What Are the Side Effects of Chemotherapy?
Dr. Lonial: Right. I mean, chemotherapy has lots and lots of different side effects. And when you think about it, it's often the fact that DNA damage has occurred that results in that transformation from a normal cell to a cancer cell. So when you interfere with DNA through chemotherapy, you're sort of doing the same thing and you hope it doesn't affect normal cells. In blood cancers that can often be a problem. You create secondary cancers as a consequence of the chemotherapy used for the first.
Andrew Schorr: Right. And I think you may know this about me. I was treated for one blood cancer, chronic lymphocytic leukemia with some chemo. And then years later I developed a second blood cancer, myelofibrosis. Was it because of messing with the DNA and another shoe dropped maybe, but that's always the risk and people develop skin cancers and other cancers. Okay. So, let's go to Nebraska. So Dr. Baljevic. Okay. So you're very involved in research. All of you are. So the name of the game has really been to try to figure out, are there more elegant ways than chemo to see how you can get an edge in killing that cancer cell, right?
Are There Improved Treatment Options for Attacking Cancer Cells Today?
Dr. Baljevic: So over the years, as we learned more and more about cells and what makes them, what drives them, and how their living cycle is controlled, we have also learned about many other genes, many other proteins. And in examples of some cancers, we have learned a limited number of these places or genes really almost control the entire process sometimes. So a good example for something like that is chronic myelogenous leukemia, for example, which has this protein BCR-ABL, that is an abnormal protein that normally doesn't exist in our cells. And with reshuffling of our genes, it is artificially created and then leads to a situation of continuous signal sending and continuous drive for multiplying, for increasing, etc.
So that's how cancer, for example, in that case starts. And we found a way to interrupt that specific protein and it's functioning with what we call molecularly designed or molecularly driven drug. And so that was sort of a poster child of that type of approach for many years. And of course, since then we have advanced in many different ways. And our understanding has increased to a point that we now have many different examples of these so-called molecularly driven cancers and molecularly specific therapies for them. Of course, as you mentioned, the name of the game these days is really tailored, specific therapy for every specific patient.
Andrew Schorr: Dr. Shah, I wonder if you could explain something to me because we patients have been hearing a lot about next generation sequencing. So we've heard a little bit about cancer genes that may be driving cancer. And then also, Dr. Baljevic was just talking about proteins. So could you help differentiate a little bit between oncogenes that have gone awry and proteins.
What Are Oncogenes? What Are Proteins Made Of?
Dr. Shah: Yeah. And it gets confusing because there are so many words that you hear in an article or from a talk and it's sort of different levels of the same processes in the cell. So a gene or the DNA is the code that is used to make the protein. So an oncogene is a gene that might allow for proteins to be made, that then cause the cell to grow more. So it's an oncology or oncogenic generating gene. And so it might be that it tells the cell, make more of this protein. And then that protein allows for the cells to grow more. So that would be something that an oncogene will do. But then if you look at proteins, those are actually the proteins that are made from the genetic code. And some of those proteins may then tell the cell, hey, you can grow more. You can proliferate more. And so the gene is the code to make those proteins. So it gets a little bit confusing because all of those things are what eventually leads to the fact that the cell grows, but it can be studied at a genetic level or a protein level.
Andrew Schorr: Okay. And there are medicines that operate on both levels, right?
Dr. Shah: Correct.
Andrew Schorr: I believe that's right.
Dr. Shah: Right. So for example, there might be medications that affect how a gene may function or not. Actually, one of the medications that was just developed for multiple myeloma, for example, selinexor (Xpovio), causes proteins to be retained so that they will actually suppress genetics, so they'll be able to suppress bad genes. But then there are other medications that actually suppress proteins, for example, of the BCL-2 inhibitors. Those inhibit the protein BCL-2. So you can actually affect either the DNA or the proteins depending on the kind of drug it is.
Andrew Schorr: Okay. So Dr. Lonial, just so we understand, these proteins or even the genes that make the proteins could be active in more than one cancer, right? So patient A could be treated with a medicine that might also be effective for treatment B with a different malignancy, right?
Can Different Cancers Receive the Same Types of Treatment?
Dr. Lonial: Yeah. I mean, I think that's one of the things that we're beginning to identify, and that is that there are some mutations of genes that are common across different cancers. So as an example, BRAF mutations occur in melanoma, BRAF mutations occur in colon cancer, and BRAF mutations occur in myeloma. And they're all the same potential change in that gene, which means that the drug that goes after it may be the same in all three. And in fact, we're testing drugs used in melanoma and colon cancer in myeloma, for patients that have that specific BRAF mutation. So, yes. And that's just one example, there are many others where you have common mutations across different cancers. Because if you think about it, there are some common ways that cells become transformed. They go from normal to malignant and turn on that switch for growth and proliferation. And so you're right. Those should be common against many cancers as opposed to unique for each cancer.
Andrew Schorr: So you're at a major cancer center and traditionally, somebody with breast cancer goes to one floor, somebody with colon cancer goes to another. Do you think that someday we'll be looking at patients as to what's driving your cancer, and they'll go to one floor, and people who have other drivers will go to another?
Dr. Lonial: Well, that may be true. But I think—so, one of the unique pieces of many cancers is that they retain some of their normal function. So myeloma is a great example of that. All the drugs that have been approved in myeloma in the last 15 to 20 years, actually don't target oncogenes. They don't target abnormal proteins, they target normal biology. And for instance in breast cancer, as you raised, ER or PR receptors are normal parts of the biology of breast cancer, of breast cells. And so there will probably be a mix between cancer-specific treatments and targets, and biology-specific treatments and targets. And I think it's bringing those two together, along with immune therapy, that will ultimately be how we cure more cancers.
Andrew Schorr: Wow. Well, I'm glad you all are scientists and you understand this. Dr. Baljevic, let me ask you about this, Dr. Shah mentioned this newer drug selinexor (Xpovio), which I know targets a protein. So let's take that as an example and where it may even apply to more than one cancer. What does it do to the protein? So you take a pill or whatever, what does it do?
What Is the Cellular Process of Multiple Myeloma Treatment?
Dr. Baljevic: Yes, that's a very good question. So just to take a moment and step back in order to make the facts more understandable, our cells are organized in a specific way in different compartments. So on the surface, we have a cellular membrane that tends to keep a sort of "liquid portion" or cytoplasm or cytosol inside one compartment. But then inside a cytoplasm, there's also a specific portion of the cell that's called the nucleus, where all the genes are sitting, and where they're situated. So as you can imagine all these different cellular processes that Dr. Shah and Dr. Lonial explained, are happening inside this confined space and inside these different areas. The nucleus is one of the key places inside the cell. And as we said, because that's where genes sit, that's where a lot of effects can end up happening in terms of normal cellular growth and processes. And then the abnormal ones that happen in cancer.
Video Clip: Inside the nucleus, there are different kinds of materials that have important jobs to maintain the normal function of the cell. Many of these materials can help fight cancer by stopping cells from growing and making new cancer cells. But they only do this important job when they are inside the nucleus. In healthy cells, proteins carry these materials back and forth between the nucleus and the cytoplasm, based on when they’re needed to do their jobs. One of these important proteins is called XPO-1. Under normal circumstances, XPO-1 helps move materials out of the nucleus when they are not needed. In some types of cancer, the cell produces too much XPO-1, which disturbs the balance of materials leaving and entering the nucleus. The excess XPO-1 proteins carry too much of the important anti-cancer materials out of the nucleus and into the cytoplasm. Once the materials leave the nucleus, they cannot fight the cancer, and the cancer cells are free to multiply.
Dr. Baljevic: So then to go back to the question of this drug, selinexor (Xpovio). Selinexor specifically inhibits this nuclear protein transporter called XPO-1 from trafficking proteins in a way that it normally does. So what happens for example, inside a myeloma cell, but not just myeloma cell as we alluded to earlier; many different cancers do actually share this same mechanism and reliance on it, and the effect could be present across multiple different cancers.
So when we give a drug like this, what happens is that in the first order, we increase the levels in the nucleus of this tumor suppressor protein. So we tend to localize it more inside the nucleus, where then a greater effect towards tumor suppression can happen. And therefore the balance goes in the direction of suppressing cancer growth.
Andrew Schorr: So what you're trying to do, take a drug to try to re-establish order within the cell, is that the right way to say it?
Dr. Baljevic: Correct. And as Dr. Shah and Dr. Lonial mentioned, this is oftentimes an interplay of many different mechanisms at the same time. It's just a challenge of understanding what is the best way of combining these strategies to suppress that cancer growth.
Andrew Schorr: Okay. Now let me go to Dr. Shah. Dr. Shah, you're a myeloma specialist. The name of the game in myeloma now is combination therapy, often. So is it the idea where a drug like selinexor (Xpovio), which is trying to establish order within the cell with other mechanisms of action from other medicines have sort of a one, two, three, even a one, two, three, four punch against the myeloma?
What Is Combination Drug Therapy? How Does it Work?
Dr. Shah: Yeah. I think if we've learned anything over the past 10, 20 years it’s that more drugs are better, for myeloma. And not only because you have an additive effect, but rather that you can also have a synergistic effect. So it might be that attacking the myeloma by different mechanisms. And this is really something we have seen very elegantly in myelomas. If you take advantage of the myeloma cell’s garbage disposal with a proteasome inhibitor, and you take advantage of maybe the myeloma surface molecule with the CD38 antibody, and you take advantage of the myeloma cell's way to grow with dexamethasone. You can really have a very potent combination of attacking the myeloma cell that really gets all three of these different ways to get to myeloma with actually very relatively few effects on the rest of the body. So I think that's one of the things that myeloma, for example, has at an advantage for its cancer combinations. But many other cancers rely on the same sort of theories.
Andrew Schorr: Dr. Shah, I know you have to leave us. But before you go, when we talk about these new approaches in combination, in new mechanisms of action like XPO-1 and selinexor (Xpovio). Things that we'd never heard of before, are you as a hematologist/oncologist excited about this for patients?
Dr. Shah: Yeah, I'm really excited about the fact that we're able to still think outside the box, ironically, inside the cell, to think of different ways to attack, in our case, the myeloma cell. That's what we focus on. But what I think this really means is that as each year goes by, we're learning more about cellular biology, more about immunology, more about proteomics and genomics and allowing ourselves to develop drugs based on that research is never ending. And we really want to get myeloma to the point where even if it's a long-term disease that's chronic, that people can have good quality of life while getting these therapies and return to the normal duration of life that they would otherwise expect.
Andrew Schorr: Okay. Thank you for all you do. And thanks for being with us today, Dr. Shah.
Dr. Shah: Thank you for having me.
Andrew Schorr: Okay. So, Dr. Baljevic. So you alluded to this, that this mechanism of action using selinexor (Xpovio) as an example, inside the cell is not unique to only multiple myeloma where you've done a lot of work. But I know there's some indication it works in some lymphomas, there's even talk of it in sarcoma, and there are other drugs, Dr. Lonial was talking about it with the BRAF mutation related to several cancers. So it seems like this understanding of these mechanisms of action, then you start to do clinical trials to see well, will it work here? Will it work there? That must be very exciting.
Are There New Studies and Clinical Trials for Multiple Myeloma Patients?
Dr. Baljevic: Absolutely. It's incredibly exciting actually. Many times we take the lessons that we learned in one example, and in one malignancy, and sometimes they can be applicable to others. In fact, over the decades in oncology field, we have learned many things on the examples of the cancers in children, and then translated almost in some examples, almost completely the principles to adults. And as Dr. Shah mentioned, it's really a never-ending experience and learning process towards the ultimate goal of trying to improve the lives and to try to prevent shortening of lives that cancers inevitably will cause with any form of cancer. But you mentioned something very important, and that's the fact that many of these things tend to be potentially a common theme across many different cancer forms.
We have seen data and we have seen activity in many different types of cancers. So beyond myeloma, a drug that inhibits this XPO-1 inhibitor, selinexor (Xpovio) has actually already been approved for a version of lymphoma. And it's furiously being studied in multiple other types of tumors, what we call solid tumors or solid malignancies. So as you mentioned, forms of sarcoma, forms of endometrial cancer, colorectal cancer, myoblastoma cancers. In fact, what's really fascinating and important, especially in the times of COVID-19 pandemic, is the fact that some of these protein interplays and transports actually are the same mechanisms that viruses depend on as they enter our cells, and as they hijack our machinery inside our cells to their own benefit.
So in fact, there are some early phase trials where drugs like that one are actually being studied in its effect against COVID-19 virus, SARS-CoV-2, to try to see if the viral replication system can be slowed down ultimately towards reduction in the severity of the disease itself. So it's really exciting time to be involved in better understanding of a mechanism such as this one, which could be really potentially applicable to many different cancer types, but also disease states outside cancers.
Andrew Schorr: Wow. That's a big deal, what you're saying, especially now as we do this program in the height of the pandemic. Dr. Lonial. So for the family touched by cancer today, excuse me. The cancer diagnosis, and you've seen it so many times, is a terrifying diagnosis. People are trying to understand it. And yet you're talking now about the leading edge of science at the cellular level and with these one, two, three punches, I talked about it attacking the cancer cell, so how can patients take advantage of this? Is it to be at a research center like yours? What role can the patient and family play so that as you're doing, sometimes basic science, how can this apply to them so that they can hopefully have a longer life?
What Advice Do You Have for Patients to Ensure Quality Care?
Dr. Lonial: Well, I think the field is moving so fast now, that it's very hard sometimes for an oncologist who treats a lot of different diseases to know what the latest and greatest treatments might be, when the data may have changed in the last 60 days or in the last 90 days. And so I think that at least my recommendation often is at some point early in your treatments, I would say sooner rather than later, get to a center that sees a large volume and has specialists in one kind of cancer. And a lot of times people will say that they, well, I focus on this or I'm a specialist in this, but there's a difference between doing it at a research center and doing it at a regular hospital.
And so I think you want to get at least at one point in your journey to one of those places where they are a research center, because there, you're more likely to get the most up-to-date approach on how to manage your specific cancer. And that doesn't mean that all your treatment needs to occur there. It doesn't mean that any of your treatment needs to occur there, but at least now you've got somebody to help set the plan and at important points in care over time, you can revisit that research center and make adjustments to the plan or changes to the plan, again, based on new and evolving data. So that's probably the one recommendation I would give for somebody who's struggling with a new diagnosis and trying to find out how to best support them.
Andrew Schorr: There's one other thing I wanted to ask you about, and we talked about it earlier about side effects, traditionally, of cancer medicines. As we develop these newer targeted therapies that are operating in such an elegant way alone or in combination is, are usually the side effects less? Or are they just different? Or however they are, can they be managed?
Do Newer Treatments Have Less Side Effects?
Dr. Lonial: Yeah. I think it probably varies. So in general, you tend to have less, what we call off-target effects. Chemotherapy has a whole lot of off-target effects, like losing your hair, getting pretty significant nausea. All the other things that go along with cytotoxic chemotherapy. Now, targeted drugs can have their own set of side effects because we do tend to push the dose to a point where you do start to see some effect on organs beyond what you're testing. But in general, they are very safely managed, and dose adjustments or dose attenuation can be used to try and minimize the long-term effects of those side effects.
Andrew Schorr: Well that's something I'll ask you about, Dr. Baljevic. And that is, take selinexor (Xpovio) again as an example, but I know there are others. Often when they're first approved, usually for the sickest people often, but the dose is a heavy dose and people may be otherwise who are worried about their mortality. But you learn over time, don't you? And maybe you could talk about that. Dr. Lonial was just referring to dose reductions. Not just for side effects, but maybe that you understand that it can be effective in combination with another medicine at lower dosages, right?
What Is Gradual Dose Reduction?
Dr. Baljevic: Absolutely. That's a very good point. And that's exactly how we, in some instances, end up learning over time. And I think selinexor (Xpovio) is a good example of that type of principle. It's really encouraging, I would say, that in general, the way medicine works on the North American side and many other places. It works by principle where just because something may be approved, doesn't mean that our checks and balances stop sort of monitoring the situation. Sometimes we learn new things as thousands and thousands and millions of patients are treated. We may start recognizing things that perhaps we did not notice, or that could not be noticed in a smaller, trials with a smaller number of patients.
But as you pointed out, selinexor (Xpovio) is a drug that was studied initially in really highly relapsed-refractory groups of patients who underwent many, many different lines and types of therapy and who didn't have a lot of treatment options left. And you also pointed out something which is interesting, and that is sort of the intention and desire to try to use a proper strength of the drug to try to elicit anti-cancer response and anti-tumor response so that we don't potentially draw an erroneous conclusion that the drug may not potentially work or any given combination.
But then as the time... And that's what happened with the initial example of selinexor (Xpovio) in the STORM study, where it was studied in patients who had a median number of seven prior lines of therapies, which is really a lot. And some of them had more than 10, upwards of 15 and more lines of therapy. So those patients have really experienced a lot of different treatments, seen every known drug and oftentimes been on different clinical trials. But then since then, we have started learning about other ways we can use selinexor (Xpovio) drug in myeloma, and that is in combination with other drugs and with different frequencies and with different strengths.
And that's very important because we have come to a point where we have been able to change the frequency from the twice weekly to what the newer study, the STORM study, which is a multi-arm phase two trial with many different novel so-called triplet combinations with myeloma drugs, is being tested and studied. We have learned that in fact, it is quite possible to give selinexor (Xpovio) on once a weekly basis, as opposed to twice weekly with a lower cumulative dose of selinexor (Xpovio), while still achieving desirable anti-cancer effects. And then what followed is a much-improved experience on the patient side and also sort of lower frequency of interventions, etc. that were needed. And I anticipate that as the time develops, we're going to continue learning more and more, and we're going to continue refining our understanding towards the best possible combination for patients, that at the same time will be aiming to give us the best possible answer against cancer, and then simultaneously allowing a good quality of life for our patients, which is always our goal.
Andrew Schorr: So you have more targeted therapies operating in combination or alone, at all different levels around the cancer cell, hopefully fewer side effects. And you're refining dosages to find the lowest possible dose, but still effective and where people can live better and live longer. Okay. So I think it's really... You've been at this a while and I've been interviewing you for years, Dr. Lonial. Would you echo what Dr. Shah said, that for people diagnosed with cancer rather than seeing it, I know it varies across different cancers, but that we can be encouraged that progress is accelerating and that there may well be newer and better treatments that can help them live longer and live better. Is that a fair statement?
The Future of Multiple Myeloma Treatment and Research
Dr. Lonial: Absolutely. No, I mean, I think we've got so much great new research. We have so many new targeted agents. We understand cancer biology so much better now, that I think the future is bright for many patients with cancer using some of these more targeted treatments.
Andrew Schorr: Okay. All right. Well, we have Dr. Sagar Lonial from the Winship Cancer Center in Atlanta, Emory University. Thank you so much for being with us. And also from the University of Nebraska, Dr. Muhamed Baljevic. Thank you. And all of you for your dedication to science, and then translating that to those of us living with cancer. Thank you for being with us today.
Dr. Baljevic: Thank you.
Dr. Lonial: Thank you very much.
Andrew Schorr: Okay. I'm Andrew Schorr. For all of us living with cancer, if someone in your family is touched by it, I think this is an encouraging report. And remember, knowledge can be the best medicine of all.