Dr. Frank Lin — Radioactive Drugs for Rare Cancers

Monday, February 24, 2020

Radioactive drugs carry radioactive substances that can be engineered to specifically target and kill tumor cells inside the body. In 2018, the FDA approved a radioactive drug called Lutathera to treat tumors that affect the pancreas or gastrointestinal tract. Now, scientists at the NIH led by Dr. Frank Lin are testing whether Lutathera can also be effective against rare tumors of the adrenal glands. Dr. Lin is a clinician and researcher focused on bringing radioactive drugs — also known as radionuclides — from bench to bedside. His work could accelerate the development of new therapies for patients with rare cancers who have few or no other treatment options.

Frank Lin, M.D., is a Lasker Clinical Research Scholar in the Center for Cancer Research at the NIH’s National Cancer Institute (NCI). Learn more about Dr. Lin and his research at https://irp.nih.gov/pi/frank-lin

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Transcript

>> Hello Dr. Lin, thank you for joining us, it's great to finally meet you. Before we get into your research as a physician-scientist I believe here in Bethesda, Maryland, I've read that you enjoy many of the museums and parks in the DC area. So, I was wondering if you have any recommendations for people new to the area.  What's maybe one of the best exhibits around that you think people might be missing?

>> Yeah, like you said I think the Smithsonian malls here are a great resource, free to the public. Personally, I have a couple of young children, ages three and five, so the museums I frequent the most are the Natural History Museum and the Aerospace Museum. Those I think have great exhibits, dinosaurs, spaceships.

>> Yeah.

>> Great for children.

>> Do you have a favorite dinosaur?

>> I don't, but my girls they do like Stegosaurus.

>> Yeah, that's a cool one, that's the one with the spikes on the tail.

>> Spikes along the spine and the tail, yeah.

>> Yeah, very cool.

>> That was one of my favorites as a kid too.

>> Great.

>> I understand you were born in Taiwan?

>> Yes, that's correct.

>> Cool, how long were you there before you moved to California?

>> My family moved here when I was nine, so over 30 years ago.

>> Do you have any memories of your time there as a child in Taiwan or any particularly memorable moments that might have shaped your life?

>> So we actually still go back. I maintain pretty close ties to there because there's a lot of family there. Actually, my parents and both of my wife's parents are also in Taiwan so we go back every year or so.

>> And you said your parents moved back to Taiwan but did they live in the US?

>> Yeah, so it's a little more typical back then I think for some of the Asian immigrants. But when we came, my father stayed there and worked there—he’s a physician. And my mother came with me and my brother, the kids. And then, so for maybe a decade or so they were doing kind of the, you know long distance, split country. But after we all went off to college my mother went back to Taiwan with my father.

>> So your dad was a doctor you said?

>> Yeah.

>> A physician?

>> Yeah, he is yeah.

>> And what about your mom what did she do here in the US?

>> She is a nurse. So that's how they met in the hospital, so I have a lot of medical connections in my family, I guess.

>> What was your childhood like in Taiwan and did anything change when you came and moved to California?

>> To be honest I don't remember too much about the childhood in Taiwan but apparently, I was told that I was kind of a bratty kid. I remember just going out to -- there's a lot of kind of open spaces close to where I lived. Just going out there. And there's a lot of stray cats and dogs back there so I liked playing with the stray animals, feeding the stray cats or running along railroad tracks.

>> Typical bratty kid stuff?

>> Yeah.

>> Yeah, we used to sneak away to the railroad tracks where I grew up too.

>> Yeah. Yeah, good times.

>> Cool and so what motivated your parents or your mom to move here with you and you said you had a brother and sister maybe or?

>> Yeah, I have an older brother and then much later a younger sister.

>> So why did you all move here?

>> So, it was mostly for the education. I mean again kind of typical for a lot of the Asian countries, there's always a thought or the feeling that opportunities are better in the US, you get better education. So, my mother brought us here specifically for a better education and better opportunities.

>> And when did you eventually decide that you for sure wanted to go into science and/or medicine?

>> So, medicine was always kind of one of those things that was you know suggested by the parents. They gave me a lot of latitude to choose what I want but it was definitely something that was I guess brought to my attention early on. So during college you know I took some science classes, I was pre-med in college, did some volunteer time and shadowing with physicians trying out the field. And it seems like you know it's an interesting field worthwhile pursuing so that's how I got into it.

>> And now you're an NIH Lasker Clinical Research Scholar in Bethesda, Maryland working at the NIH Clinical Center and the Center for Cancer Research at the National Cancer Institute.

>> Right.

>> So what biomedical problems are you working on? Why did you come here?

>> I'm interested in doing cancer research. I kind of took a really winding path to get to where I am. So first of all from college even though I was pre-med, I also had a lot of interest in computer and computer science. So when I graduated college, I was actually undecided between computer science and doing medicine. I kind of did something that was a combination compromise between the two at first so that's how I ended up in Utah, the University you Utah. I did a master's in medical informatics which is a good combination of CS, computer science, and medicine. I did that for two years and then after that felt that I did indeed want get into clinical medicine. And so from there I went to medical school in Wisconsin. And then kind of typical of me I was undecided what medical specialty I wanted to get into after that so I chose a specialty that was the broadest, so I did internal medicine. And then after that I got to know some people in my residency who are nuclear medicine physicians. So nuclear medicine physicians they work with radioactivity but in the medical setting. And kind of two broad areas of that is they do imaging with radioactivity so PET scans—positron emission tomographies—and they also do treatment with the radioactivity.

>> Yeah, that was new to me in looking at what you do, I didn't fully realize what—everyone I think, a lot of people know there's imaging but they don't necessarily know what's involved with treating someone with radiation.

>> Yeah, so I think the radiation treatment that most people are familiar with is probably external beam radiation. So that's a different specialty, that's radiation oncology. That's radiation that's provided externally usually via some sort of you know x-ray beam generator and the radiation is given from the outside. So treatment when nuclear medicine physicians do it, the difference is that the radiation is given internally, systemic.

>> So what kind of form does that take? So something's injected, that has some kind of radioactivity to it?

>> There are different ways of getting the radioactive material into the body. One method is ingested so for like radioiodine for thyroid cancer it's a pill that you could take. And then some of the other ones like the ones I'm working with right now, Lutathera for instance, that is given as an infusion. And then there are others that are say injected into the body cavities, peritoneal cavity or during surgery, intraoperatively. And so there's different ways of administering them.

>> What cancer types do you focus on in your research?

>> Currently I'm working with a rare disease since you know at the NIH we have a good collection of rare disease patients. So I'm working with pheoparagangliomas and pheochromocytoma patients at the moment.

>> So what is that?

>> These are endocrine tumors. Pheochromocytoma is a tumor of the adrenal glands. But the characteristics of these tumors is that they secrete a lot of catecholamines which are chemical hormones that's similar to adrenaline. So patients who have these tumors, if the tumor is secreting these hormones it's like they're under a constant adrenaline rush. So you have symptoms related to that so you can get high blood pressure, high heart rate, facial flushing. And it's dangerous because as you can imagine you're exposed to these hormones for a long time with you know high heart rate and high blood pressure that puts you at risk for things such as strokes, organ damage such as heart damage, and so forth.

>> Yeah, I imagine it takes a big toll on your whole system being kind of ramped up all the time.

>> It does yeah and that's kind of exactly what's happening to these people.

>> So out of all of the people who have, I probably will not say this correctly pheochromocytoma or…

>> That's right.

>> Paraganglioma.

>> Paragangliomas, yes.

>> How prevalent are those tumor types in the general population?

>> So these are rare tumors, in the US there's probably 3 to 500 cases every year. I mean when I was in medical school and learning about this tumor, the textbooks teach us that average primary care physicians, such as an intern is a family medicine doctor will probably see one or two in their career. But here in the NIH it's not so rare. But for this program I'm working with Dr. Karel Pacak of the endocrine branch and he's a world expert in these tumors. He gets referrals from all over the country, all over the world even. And we actually have about 3 to -- maybe 3 to 400 patients every year. So it's a very concentrated population versus the outside. Which is another reason why the NIH is probably the only place in the world that this clinical trial can be conducted and done just because we have the patient population that probably exists nowhere in the world.               

>> Do you work specifically with the undiagnosed diseases program here at the NIH?

>> So there's a rare tumor program, rare tumor clinic here located within, you know, situated within NCI. And currently I worked I guess most closely with that program. Although my research focuses on the modality of radioactive radionuclide therapy treatments rather than any particular tumors. But it just happens that you know for right now several of my projects does involve rare tumors. But some of the work that's being planned you know it's in prostate cancer for instance which is of course not a rare tumor, a very common tumor in fact. But there's also plans to work with lung cancer, colon cancer in the future.

>> Rather than I guess focusing on picking a certain disease to work on you're looking at the available technologies and treatments and trying to expand what's available to doctors or explore how they work and figure out new techniques for doing radio-medicine?

>> Yeah, so part of this -- so the way these agents work is that they are targeted agents, meaning that the agents are designed in a way that they bind to specific tumor targets whether it be a receptor or a surface marking the tumor. So a lot of the agents work by hitting select targets and then kill tumor cells via actions of that target. So by binding to the tumor cell the agent could cause some downstream effects in the cell, cause some chemical changes or causes some signal transduction in the cell. But the agents I work with, the targets just -- the purpose of the target is to bring the agent close to the tumor. And once the agent is close to the tumor proximity is all that's needed to kill the cell. So really, I'm just using those as a pathfinding rather than relying on the activity of the agent itself.

>> Is imaging a part of what you're doing or it's more the action against the tumor cells?

>> So imaging is actually a pretty big part of this. A lot of the agents in radionuclides—depending on what kind of radioactive decay process you undergo—it could be a treatment agent or an imaging agent. One good example is the agent that I'm working with in my clinical trial right now which is a lutetium dotatate. So the targeting agent for that is the dotatate, which targets the somatostatin receptors in tumor cells. But depending on what you attach on the other end of the dotatate, it can be either a treatment agent if attached to the lutetium 177 which is a beta-emitter, it emits beta particles. Or if you attached it to a positron emitter such as gallium 68, a positive emitter enables it to be imaged in the PET scanner, so it becomes an imaging agent. So a lot of these are what we call theragnostic agents that it has both a therapy and a diagnostic imaging use.

>> The beta-emitters is that also theragnostic, there's imaging associated with that?

>> There are many different kinds of radioactive decay, so there's alpha emission, alpha-emitters, beta-emitters, gamma emitters, and others. Each of these radioactive particles have different properties which makes them good for either imaging or treatment. An agent like lutetium has both beta and gamma emission which means that the beta particles it's a treatment particle but because they also have gamma emissions it can be imaged using a gamma camera, a spec camera.

>> Okay.

>> So the lutetium dotatate itself is a true theragnostic agent in that it has treatment and diagnostic properties.

>> So that I believe I have a brand name here, so I believe that's already FDA approved drug?

>> Right. So the tradename, the brand name is called Lutathera and it was just approved January 2018.

>> Oh wow that's new.

>> Yeah, it's very new. I mean the field has been around for quite some time but it's only very recently within the last five or six years that it's really starting to pick up. But yes, so the Lutathera is approved in the US but in a different tumor type. So it's approved for neuroendocrine tumors, abdominal neuroendocrine tumors.

>> So what is your goal with this clinical trial? Are you testing to see if it works on other tumor types or if it's safe in different types of patients or what are the primary outcomes you're looking for?

>> So this will be classified as a phase II clinical trial. So the main goal of this trial is to look at efficacy. So it will be to see if the Lutathera how good it is at controlling the tumor in this patient population. So the main goals, the primary objective of the study is we are looking at progression-free survival, whether we can extend that or increase that by about 20% at the six-month mark.

>> Cool. And why did you pick that number, 20%?

>> So we're working with the statisticians, the 20 came from -- so it's a number that we feel like will be clinically relevant that you know if we tested a new agent if it's only able to create an additional benefit of 5%, then it might be too small to make a difference in terms of you know having the oncologists or endocrinologists actually use the agent. So I feel like we need a big enough of a proven benefit for this to be worthwhile trial. Because conducting a clinical trial you know is very expensive so we wanted something that actually has significant benefit over what's existing right now that's where that number came from.

>> And this is an open, currently recruiting clinical trial that you're in?

>> It is. The program has been open for almost a year now and yes, it is currently recruiting.

>> So what are the sort of very, I guess, top-level requirements, people with this particular type of rare tumor that's who you're recruiting?

>> So these tumors if they are localized the first treatment is usually surgical. So I'm in particular looking for patients for which surgery is not possible. Whether either because the disease has spread or metastasized to other places and you have too many disease sites in the body and you can't just go and cut everything out. Or the tumor is located in the location that's say too close to other critical organs or major blood vessels so that they're surgically not operable. The big criteria are patients who are not surgical candidates and also too patients who are progressing their disease. That you know by doing serial imaging the disease is getting worse, tumors are getting bigger, increasing in the number of lesions. So these are the main people that I look for in my trial.

>> How can people who hear about that, how can they participate? How can they find out about your trial?

>> So they could find out general information about the trial through clinicaltrials.com.

>> Or dot gov or dot com?

>> Dot com, dot gov sorry.

>> Okay.

>> Clinicaltrials.gov. If you do a search for pheochromocytoma and Lutathera or lutetium dototate that'll probably bring up the trial. And then on there will be the contact information for my research nurse and the trial coordinator. Or they could always email me directly, I guess.

>> Yeah and for those patients or people who are just interested to learn about your research how can they find out more about what you're up to and if you have any new clinical trials that are open?

>> I believe I'm on the NIH CCR website now that would always have information about my current trials, currently open trials. And also, I think there's a small short biography section about kind of what my research interests are and what I'm doing at the moment. So that would probably be -- that would probably be the best source of information.

>> And if it all works out in a positive manner then would the next step be a phase III trial, like a larger trial or what would the next steps be?

>> So that would typically be how it would be done but in this case since it's such a rare tumor we're hoping that this trial will be enough, will be the registration trial that will be enough to get us FDA approval. It wouldn't be approval of a new agent it would be an additional proof indication for a pre-existing agent. And because this is a pretty rare disease the feeling is that this might be enough for us to get that new proven indication.

>> Are there other radionuclides that you're also working on?

>> Yes, my whole research is on like I said the modality of radionuclide therapy so there are several others that's being worked on right now. The most immediate one that's coming up is probably PSMA, which is prostate specific membrane antigen. It's something that's overexpressed in prostate cancers. So like the Lutathera this is also a theragnostic agent. So if it's attached to lutetium then it's the treatment beta particle but it can also be attached to gallium 68 for the positron emission in a PET agent.

>> Have there been any big projects or any particular radionuclides that you are working on for one purpose, but it just didn't work out?

>> Not so far. I think that's probably because I am working with agents that already been taken out by a company so there's already been some evidence of efficacy and not only that there's already a commercial backer. So the agents I'm working with right now are already much further along than if I was say starting from scratch building the chemistry and the molecule from the beginning.

>> So a couple of things that I read that you're very interested in your research is using alpha particles.

>> Yes.

>> And the auger effect. So what is in alpha particle and what do you do with an alpha particle, what's the use of that in your research?

>> Like I was saying before, there's different types of radioactive decay since some of them produce different types of particles and radiation. An alpha article is in essence a helium nucleus, it’s composed of two protons and two neutrons. Whereas a beta emission, beta particle is essentially an electron. There is a very big difference in the masses of these two particles with the alpha particle probably being somewhere around the order of 7 to 8,000 times greater mass than the beta particle. So the way these agents kill tumor cells is they get close to a tumor cell and as part of spontaneous radioactive decay, these particles gets ejected from the site of radioactive decay and they kind of bombard their entire surroundings, it's almost like a cluster bomb effect. And they achieve tumor kill by damaging the DNA of the tumor cells either directly or indirectly. So you can imagine if you're—you know, it's similar to shooting a bullet versus shooting a cannonball. The particle that you're shooting out is a lot larger, the chance of that hitting your target, the tumor cell's DNA is a lot greater. So alpha particles have a much higher what you call linear energy transfer (LET) and that's just a term describing how much damage, how much energy can be transferred to the surrounding tissue—to the surrounding tumor cells. So alpha particles have one of the highest LETs so as a treatment radioactive particle it’s one of the best ones around. But it's also one of the hardest to harness because of the chemistry involved and because of the toxicity involved in handling such a powerful particle. My initial trials and projects use lutetium which is a beta-emitter. In a sense I'm using those as a buildup to what I eventually want to do which would be more projects, more trials, working with alpha particle agents.

>> Are there any existing alpha particles used in theragnostic currently?

>> So there's one right now. So it's the only approved alpha particle treatment agent and this is radium 223 which was approved about five or six years ago in prostate cancer.

>> Wow so there's just one out there?

>> There's just one out there right now yeah.

>> And so these particles they -- and they probably, they act over a very short distance right but they're very destructive so your goal is to get them real close to the tumor so they just hurt the tumor cells and limit the toxicity?

>> Right, right. So I mean comparing just the alpha and beta particles, the beta particles because they're smaller they tend to go through more matter before depositing their energy. So the good thing about that is that if they attach to say the outside of a tumor mass, they have the potential to penetrate deeper into the tumor. But kind of the flipside of that is that they also have more potential to damage normal tissue. So one of the benefits of the alpha particle is that the range is really short, usually just a few cell widths whereas as the, you know, the beta particle could go for several millimeters.

>> That's a big difference yeah.

>> That's a big difference yeah. So the alpha particle is a lot more targeted but at the same time they're much more destructive.

>> What is it that they're actually doing, the protons are hitting other protons or what's happening at the site of damage of the DNA?

>> So radiation damage to the cell can happen directly or indirectly. The direct way would be the alpha particle actually making contact with DNA, some molecules of the DNA causing changes in the target DNA which eventually results in DNA breaking either with the single-stranded or double-stranded DNA. It's typically thought that the double-stranded DNA breaks are the more lethal type and the alpha particle has a greater probability of causing double-stranded DNA breaks.

>> If it's a single strand break it can maybe repair itself?

>> Yeah, so the cell is pretty good at repairing DNA damage, so the cell has pretty sophisticated mechanism of repairing single-stranded DNA breaks using the other intact DNA as a template. But if the break is double-stranded DNA break then the repair is not as efficient, and the kill rate is a lot higher. You know these particle kills will cause DNA damage indirectly by the generation of free radicals. So there's a lot of different other things in the cell the radioactive agent could hit something else in the cell and causes ionization, other parts of that cell. And that could create free radicals which in turn can go to DNA and cause DNA damage.

>> One of the other things that I also saw that you're interested in is the Auger effect. Could you maybe talk a little bit about what is that and how do you use it?

>> So, it's pronounced O-J.

>> Oh, thank you.

>> Like the orange juice, OJ.

>> OJ.

>> That's how I remember it, so it's Auger electrons. Essentially another type of radiation that's emitted through radiation, through radioactive decay. And the thing about Auger electrons is that they have extremely short range, even shorter than the alpha particular, whereas the alpha particle usually goes from a few to maybe ten cell lengths. The range of the Auger electrons is in the range of nanometers so it's intracellular. So, for these agents to work they have to essentially be inside the cell, so they have to be right next to the DNA because their range is so short that even say they're outside of the cell they're too far away from the DNA. The benefit of these is, again, because of the proximity because you have to get inside the cell, they cause a lot less damage to other healthier cells if you can target it so that they only go into the tumor cells.

>> So I guess a lot of this you're using imaging to see where all the tumors are and then so you know where to send the treatment, the radionuclide?

>> Yes, yes. In fact, for the lutetium dotatate, for instance, you always do a gallium dotatate scan to see if the tumor, if the agent goes to the tumors. So the gallium dotatate scan is essentially an eligibility criterion so they have to be positive on the scan because if they're positive on the scans then you have a fairly good confidence that the treatment agent would go where the scan agent goes. Kind of by proxy then you have a pretty good confidence that the treatment agent will go to the tumors if they light up on the gallium scan.

>> Are you doing any Auger research currently?

>> So not yet, it's being planned and there are a few candidates that are being discussed but you know one step at a time so.

>> Totally. Well how will you go about—what’s your process for identifying an alpha particle or an Auger effect that you're going to try to harness for a theragnostic?

>> It always starts with a target. So for the Lutathera, for instance, the lutetium dotatate that targets the somatostatin receptor. A good target would be something that is expressed a lot, overexpressed in the tumor cell but it's expressed in a limited fashion on healthy non-tumor cells. So I think the first step in identifying a good agent is finding a target that has good tumor to background ratio we call it. And then once you have identified a good target and then you can work on the chemistry, from there develop the agent through you know preclinical studies, human studies, and clinical trials. So far, we've been, because my program is just starting out, we've been working with agents that have company backing industry partners. So we've been using those agents in our trials. But eventually as the program I think grows and gets more established I hope to start looking at newer agents that are kind of thought of, discovered and worked on here at the NIH.

>> So what's involved in the chemistry portion of that whole process?

>> There are radiochemists that work with that, that's not my area of specialty. Sometimes with radioactive decay the atom actually undergoes elemental changes. So because of loss of protons usually it changes from one element to the other. As you can imagine for chemistry a lot of it depends on you know the bonds that hold agents together. It depends on the number of electrons, the kind of covalent bonds it forms with other molecules. So when the element changes a lot of the chemistry also changes so there's a lot of work with that.

>> Yeah, I guess you have to think through what are the possible things that might happen here and how do you control them?

>> Yeah and you also want an agent that could be eventually industrialized, and production be ramped up. So if you have to synthesize a molecule using a process that's very laborious—takes 10 hours to make—then that's not an agent. Even though it might work in the lab, it might not ultimately be useful in the clinic because it can't be widely distributed. So there's also a part of it that is optimizing the chemical synthesis process for those types of things.

>> And I guess there's probably some radiochemists here at the NIH that you can collaborate with when needed?

>> Yes, so we work with an excellent group of radiochemists. So like many things at the NIH there's pretty good support from you know other groups doing similar scientific research that you can collaborate with. And we are fortunate to have a good radiochemistry group here.

>> And how long ago did you come to the NIH?

>> I've been at the NIH for about eight years now, again kind of a winding path getting to where I am now. But I came to the NIH in 2010 with the NCI but for the first six or seven years I was part of the extramural NCI, so I was in CTEP which is a part of the NCI that provides grant funding or manages grant funding to other investigators. So the NCI is broadly divided into extramural programming and intramural program. The intramural program where I'm now it's the part that functions almost like an academic center in itself—it has labs, has a clinic, does research. Whereas the extramural NCI gives funds and grants to other institutions to enable research. So for the first six years in the extramural part, when I was with the cancer imaging program, the kind of things I was more involved with is thinking about identifying gaps in in the field and also managing some grants. So a much higher-level view of the field.

>> Sort of planning research but not necessarily doing research at that time.

>> Right. And not planning research on an individual level. We are more in charge of the roadmap of the field, trying to see where the field should go or needs to go. So it's a much, much, much bigger picture view—a much bigger picture of responsibilities that I had for you know the first six or seven years.

>> That sounds interesting. And then only within the past couple of years—maybe it started a little earlier—you decided to make a switch and get back into doing your own research?

>> Right. So with the Lasker program I transitioned into the intramural program and that only happened in December of 2016. So instead of kind of watching others do research and guiding them, now I'm doing my own research and have my own lab and so forth.

>> Why did you decide to change?

>> Fate, I guess.

>> Yeah?

>> It's not really something that was planned out from the beginning. I came to the NCI straight out of fellowship. After I finished my internal medicine residency, I took nuclear medicine residency at UC Davis, the University of California Davis. And then after that I did a PET/CT fellowship at Stanford. I came to the NCI straight out of my Stanford fellowship. It's probably not the typical job one gets after a fellowship I think and it's just kind of by luck that I got a position. So after I was finishing up the fellowship, I was seeing what jobs were available. There were some clinical positions opened in the academic centers, but there was also the position at the NCI which was very unique, because like I said you get to kind of be at the center of the research, you get to influence where the field will go, and you get to shape the future of the field. So that was very exciting to me so I kind of jumped on the opportunity. That experience helped me gain a much bigger view of the state of cancer research in general in the US. And I think having started out with that bigger picture view, it helped me kind of see what is needed to be done much better if I were to start the more traditional which is you start doing your own research on an individual level. And then as you gain more experience with time become more senior, then at that point you gain the bigger picture view. So I kind of did things in reverse. But I transitioned to the intramural program because one, I was still [inaudible] getting to do their experiments. And then the Lasker program just presented the opportunity for me to do that.

>> So what is maybe unique about the Lasker program?

>> The Lasker program I think it's unique, it's a combination program that has kind of two parts. So the first part is within the NIH, so you spend I believe five years in the intramural program. And then for the second part, you have the option of staying within the NIH and become a tenure investigator if you pass tenure review. But there's also the opportunity to essentially get an outside academic position and take some of the funds with you. So I think it's the first program of this type in that it gives you that flexibility. But it's also very good because it's very supportive. So it's meant for young investigators, the program requirements have changed a little but I think at the time I applied it's only for investigators who are within 10 years of their primary residency training. So it's designed for people early in their career and it's designed to kind of help and support them make that transition to independent investigator.

>> And so you’ve got just a couple more years left before you have to make a decision?

>> I started in essentially 2017.

>> Okay.

>> So a couple, a year and a half in.

>> Got you, a few years left.

>> Yeah, so I'm still in the early half of the program. Yeah. And I guess the other unique part of this is that as its namesake, it has strong ties to the Lasker Foundation you know so there's a lot of programs, training opportunities that are associated with the Lasker Foundation. As Lasker scholars we are also invited to the annual Lasker award presentation. So you know you get some perks and you know get to meet some of the Lasker award winners, many of which you know go on to become Nobel Prize laureates. So there's that connection that's also unique to the -- and the networking opportunities.

>> Has there ever been a moment you were at the award ceremony or any other events and you were just starstruck like, ‘oh there is that researcher who does this that I'm so excited to meet but I'm scared? Anything like that where you’re starstruck?

>> I've only been to one so far. I got to meet the NCI director there or the acting director Doug Lowy you know and I got to talk to him, shake his hand. Probably not something I will have the opportunity if I wasn't part of the program and was there.

>> Yeah. Are there any other researchers that sort of give you inspiration either for their leadership abilities or their peer research that they're doing that inspires you?

>> I take a lot of inspiration from my current lab chief who is Dr. Peter Choyke, he's always been very supportive of my research for one. I'm really impressed by what he's been able to do here. You know he has a very large program with molecular imaging. He's just been able to pull together a lot of different trials from many different specialties and really advance the field.

>> So what are some of the biggest challenges that are going to be facing you over the next few years in your research?

>> When I started the Lasker program and started doing research with radionuclide, one of things I wanted to do was to be able to integrate the treatment better into current medical oncology practice. One of the challenges facing the modality, this treatment modality as a whole, is that although the agents are often times you know scientifically sound, effective, very low, very good side effects profile—not a lot of side effects—I think they haven't been utilized in clinic as much because medical oncologists are not as familiar with this treatment modality. My solution to that was to become a medical oncologist myself, so for the past year and a half or so now I'm being further trained doing a medical ecology fellowship here at the NIH. And the reason I do that is like I said I wanted to be able to integrate the two fields better. What better way to do that then you know having a foot in each specialty? And having the medical oncology background would also allowed me to test out combinational trials, do combinational clinical trials. For instance, combine the chemotherapy with this radionuclide therapy, combine the other targeted agents with DNA repair inhibitors for instance. Combining that with the radioactive agent which causes DNA repair. So there's a lot of these combinations that somebody who has just training in nuclear medicine won't be able to do by themselves. Because of this part of the challenge has been time—trying to you know have a full-time job and also do the fellowship and learning essentially a new field. But I'm hoping that you know with the end of the fellowship coming in about six months or so I'll be getting over that part and have more time that I could dedicate to the research and running the trials.

>> Do you think that we're going to be able to cure all types of cancer anytime in the future?

>> Well that's a big goal. I think maybe in some individual cancers it could be possible. In fact, in some of the cancers if you capture early enough, earlier stages then some of those cancers are curable. In cancers that are spread or metastatic cancer it's a lot more difficult just because cancer cells, tumor cells are smart. They evolved like other organisms are. Whenever you come up with one treatment that seems to work, over time tumor cells evolve and they come up with strategies and become resistant to your treatment. So it's always a fight of different evolutionary forces.

>> So you -- like you said you had this really unique opportunity to get sort of the bird's-eye view of the field of cancer research. Are there any common mistakes that you see maybe medical oncologists or researchers make in their careers?

>> I think one thing that is common is that scientists, investigators they are focused on just the immediate future. And a lot of it is because I think the way the infrastructure of scientific research in the US is. Because a lot of researchers have to secure funding for their labs, so their most immediate concern is always you know securing the funds for their projects. So, their emphasis tends to be those short-term goals. But I think with some agents, the problem they run into is that once an agent gets developed the path to step up the production, to make it more generalizable and clinically usable—that part is oftentimes not thought about or considered at the beginning. I think if people take like a bottoms-up approach almost to think where the agent, where the clinical need is, where the agent needs to be in terms of getting FDA approval and getting a company to sponsor or to take it up commercially. And then almost work backwards from that or at least consider that in the initial scientific experiments, I think that part is missing.

>> Is there anything else you might like to share with the world about your research or life at the NIH, what it's like being a scientist and a doctor at the same time?

>> I just want to say I think the NIH is a great place for scientists, physician scientists who are very interested in research. The environment here is very supportive, you do get a lot of support both financially and resource wise. You really have I think the freedom to pursue whatever you want scientifically. I would encourage anyone who is interested in doing biomedical research to consider the NIH.

>> Excellent. Well thank you Dr. Lin.

>> Thank you, good to be here.