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aha! moments in cancer treatment

I think we can all appreciate those “wow, this is amazing” moments of life. They can be many and varied, but at some point everyone has those intense feelings of gratitude and satisfaction. I’ve had a few of these moments lately when reading about immunotherapies for my research. I love the idea of using the defenses and machinery that our bodies already possess to fight off foreign invaders, such as cancer. The human body is pretty extraordinary — and the ways we fight off cancer are as well.

One of the steepest learning curves for me has been remembering the names, classes, and side effects of cancer drugs. There are SO many cancer drugs out there, and more get approved for clinical use every single day! With the help of some charts created by my PI (like this one published in the New England Journal of Medicine) and some really extensive notes, I feel way more comfortable with cancer therapies than when I started. Most people have heard of “chemotherapy” as a treatment for cancer. For years, chemotherapy has long been the go-to induction treatment for many types of cancer. I think of chemotherapy as the biological version of carpet-bombing – it is very limited in specificity and comes at a cost of collateral damage. Chemotherapies (literally “chemical treatments”) induce apoptosis, or cell death, of cancer cells through many mechanisms. They may interfere with DNA replication or alter the metabolic machinery necessary for providing fuel for cellular survival and reproduction. Chemotherapy drugs are most efficacious against cells that divide rapidly (i.e. tumor cells) but come with many of the side effects we associate with cancer – fatigue, loss of hair, dry skin, and general myalgia. Traditional chemotherapies are still used but mostly in combination with newer drugs and at lower cumulative dosages.

The advent of targeted therapies for cancer has redefined the specificity of cancer treatment (the word “targeted” gives it away). These are usually small molecules or antibodies that target kinases, or phosphorylating enzymes, that are overexpressed on cancer cells. Targeted therapies may work intracellularly through small molecules that slip inside the cell and stop cancer-promoting enzymes or extracellularly by recognizing receptors involved in tumor pathogenesis. Instead of using a carpet-bombing approach, targeted therapies are designed to selectively target cancer cells. One of the targeted therapies we study is trastuzumab (Herceptin). This is a monoclonal antibody (an immune system molecule that recognizes one complementary receptor) that binds HER2, a kinase expressed on cells. HER2 is overexpressed on HER2+ breast cancer cells, among other HER2+ cancer types. Once trastuzumab binds HER2, it inhibits a signaling pathway that normally promotes cell survival. Trastuzumab is one example among many, many other types of targeted therapies used to treat cancers. Targeted therapies have literally saved hundreds of thousands of lives and will continue to do so as scientists “fine tune” their targeted activity.

Now, immunotherapies. These are the current Holy Grail of cancer treatments. I am still learning a lot about the biology behind immunotherapies. Surprisingly, most immunotherapy treatments don’t care at all about the cancer cells. Instead, they focus on the cells of the immune system. We have cells in our bodies called T cells that essentially patrol for foreign invaders. Dendritic cells, another type of immune cell, “show” the T cells pieces of degraded protein, or polypeptide. The T cell then either recognizes the polypeptide as a normal part of the body or as foreign. If it recognizes it as foreign, the T cell will become activated and initiate an immune response. This is a normal process and keeps our bodies healthy and free of disease. Except in the case of cancer. Like most things, the immune system has its own set of checks and balances. The T cells (those monitoring cells that give approval for an immune response) have a protein called programmed death-1 or PD-1. Other immune cells have the receptor to this protein called programmed death ligand-1 or PD-L1. These two molecules fit together like puzzle pieces. If the T cells inappropriately initiate an immune response, cells with PD-L1 will bind PD-1 and effectively stop the T cells from killing anything.

Unfortunately, some cancer cells overexpress PD-L1 so that the immune system is always put on hold and does not attack them (which it should because they are foreign). The cancer cells become “hidden” from the immune system and continue to thrive and reproduce. But, aha!, some scientists much smarter than me once asked, but why doesn’t the immune system recognize cancer cells as foreign? And after a lot of research, thousands of pipette tips, and some vigilant clinical trials, today people are being cured by their own immune system. A new cancer drug, pembrolizumab (Keytruda) is a PD-1 inhibitor that binds to PD-1 on the T cell that normally functions as a brake (or as a signal to not kill). It is like sliding in another puzzle piece so that the original cannot fit anymore. This means that those pesky cancer cells that overexpress PD-L1 can no longer hide from the immune system. Pembrolizumab and nivolumab (Opdivo) have had remarkable response rates. A recent paper published in the journal Science (here) demonstrated how these immune checkpoint inhibitors may be used to treat cancer cells with a shared genetic deficiency. This recent publication and growing knowledge of immuno-oncology, cancer genetics, and precision medicine are transforming cancer treatment. I think this stuff is pretty cool, and I always leave feeling amazed, humbled, and grateful for the work that people are doing to save lives.

If you think this stuff is also pretty cool, check out the New York Times dedicated section on immunotherapy. A few articles from my lab are here and here as well. Thanks for reading!

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thoughts on a beach

There are fewer things I want more than to become a physician — truly, when I survey my life for my heart’s deepest desires this worthy role sits at the fundamental core. But then I ask myself, why do I want to be a physician? I have always thought it not only wise but necessary to question every little thing. I was once infatuated with philosophy and while I don’t read it as often as I used to, the inquisitive and questioning nature it taught me never left my mind. So I ask myself – why do I want to be a physician? The answer is complex yet innately obvious to me. There is no short, one-lined answer for my reasons but instead a summation of all my unique life experiences that have lead me to this decision. I have explored other career options that align with my passions: I’ve thought of becoming a professor and teaching chemistry; I’ve considered going to graduate school and being a lifelong researcher; I’ve discussed working in industry as a chemist; I’ve toyed with the idea of being a science writer and journalist. I love teaching others and guiding people to discovering knowledge about themselves through learning difficult ideas and concepts. I think learning is one of God’s greatest gifts to man – I truly believe there is nothing that cannot be learned given enough hard work and time. I am amazed by the human body, the biological systems that work harmoniously within, and the chemistry that, literally, composes all of life and the physical universe. I love reading literature because I get to live through the stories of so many different people, experience their culture and hear their thoughts. I like doing science because it teaches me how to think creatively about the problems that are causing disease and illness. Research brings together the basic science of biology and biochemistry and allows me to do the thinking, the dirty work, and hopefully, discover the solution to a patient problem. But in my searching for the vocation I want to commit my life to, each of the prospective alternatives fell short in a specific and important way. For most, I could not help people in their most vulnerable state. I was missing the intimate and trusting physician-patient relationship that I was attracted to in the beginning. Medicine brings together all of the things I have found myself passionate about for such a long time: passions true to my being, woven into who I am and who I will want to be for the rest of my life. For me, becoming a physician has nothing to do with prestige, honor, or pay. No one in my family is a physician and I’m not being pressured down this career. It has everything to do with using the skills I’ve been blessed with to do the things I love to help others live a healthier life free of disease. I don’t just want to be a physician; I want to be an advocate, an encourager, a teacher, a confidant, a scientist, and a calming, present voice amidst the stormiest times of my patients’ lives. I want to inform and educate others about science and health and learn from those around me in every way I can. I want to write and read and maintain who I am in the long nights and ceremonious mistakes that a life of practicing medicine promises. I want to some day be a wife and a doctor and execute both in the best manner possible. These are the things I envision and hope for my future. So when I feel like my pathway becomes blurred by the constant lull within me to be better, do better, and achieve more I step back and ask myself – to remind myself – why I want to do this. I am journeying this path in life, not for anyone else, but to satiate my unquenchable desire for knowledge and service, challenges and relationships, through triumph and defeat – and that alone makes this pathway my own. I will not lose myself in the circuitous trap of comparison but will instead find myself lying with peace on this beach, reading legendary Nabokov, and dreaming of my future as an endless learner, a trusted confidant, and, ultimately, a healer. 

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travels

I’m not sure I’ll ever be able to describe the experiences I had when I was away. People talk about traveling, and the impact it has on your life, and you don’t believe them until you actually have that transformation yourself. You grow up in the comfort of your own country with people that mostly look like you and act like you. For my personal childhood, these people were pretty homogenous to me – in appearance and ideology. When I went to college I realized how much I appreciated learning from other cultures and from people that think differently than myself; I adored meeting those people and developed an appreciation for our differences. This December, I seriously sat down with my dad and asked if I could travel abroad for a Maymester. Going out of the country, admittedly, scared me. After some convincing and coercing, I was given blessings to go to Ireland and England. I would be studying public health of three countries and was ecstatic to learn of an area of healthcare I was less familiar with. The spring semester came with its challenges of exams, family life, a new research job, and college in general but before long I had finished my second year of college and was packing to travel across the pond. I can admit that I really had no idea what I was getting myself into – and that is part of the beauty of it all.

It is overwhelming to think of how to write about my experiences. I couldn’t possibly try to start from the beginning to the end, and I’m kicking myself for not keeping a journal going throughout my journey abroad. Truthfully though, I was going pretty much nonstop and would cherish the few hours of sleep I would get each night. I didn’t find time to write. When I think about what I learned on this trip, so much comes to mind. I’ve decided to just write of my experiences as I think of them – so my first one is below!

I feel very deeply that my experiences abroad will make me a better future doctor. Public health is concerned with the health of the masses – not the privileged, or the wealthy, or the exceptional, but of every man and every woman that is deserving of health. A public health perspective is not focused on individual treatment but on ensuring health opportunity for every person. This means that the woman in poverty with a newborn child is just as deserving of health as the wealthy businessman with a nice sportscar. On the first three days of our trip, I learned about the public health infrastructure in the United States, Tennessee, and Nashville. The Commissioner of Health for Tennessee spoke with passion about healthcare for all, not just in the states, but globally. He spoke of not just improving health but health equity. I learned of government programs that aim to improve the health of vulnerable populations – women with children, the impoverished, elderly people, people in rural populations. I observed with excitement the earnest desire that our public health professionals have to alleviate disease and illness and ensure health for all people. I walked the streets of Nashville with a nonprofit organization and talked to people living in homelessness – people I had often passed. I learned of how homeless people are even more susceptible to mental and physical disease than those that have a place to rest their heads. My heart became more compassionate, more understanding, and more heartbroken for the lack of systems we have to care for people that need it most. I thought of how homeless people were stigmatized and criminalized. What I realized most was my own attitude towards them. People – despite color, wealth, social status, illness, or any other factors – are just people at their core. They share the same anatomy, the same biochemistry happening inside their bodies, the same capacity for illness, the same emotional vulnerabilities. People are people, and sometimes as a society, we don’t treat them that way. People are stigmatized for mental illnesses, HIV/AIDS or other STIs, disabilities, and a menagerie of other diseases. In my own country, I noted these discrepancies. As I traveled overseas, I had lectures on public health in the UK and in Ireland. The same problems exist elsewhere, but I do feel these countries have developed more inclusive health systems. Without getting into the (complicated) details of the healthcare systems across the pond, the UK has a single-payer system that is funded through tax dollars and offers coverage to all citizens. The UK also ranks #1 among healthcare delivery, accessibility, quality, and timeliness; unfortunately, they rank second-to-last in health outcomes (second only to the United States). So, of course, the UK has its problems in improving the health of populations but at least has developed a sophisticated and inclusive (for the most part) healthcare system. Ireland has a much more convoluted healthcare system that has a public component where all citizens get a medical card they use to get public healthcare, and a private component where paying citizens can get private insurance and faster healthcare services. Interestingly, the public healthcare services are more desired than the private because of more extensive expertise in the public hospitals. Nonetheless, all of this healthcare talk is really exciting to me and something I want to be more involved in but probably boring for everyone else… The culmination of my experiences abroad lead me to realize that whether or not you believe healthcare is a right or a privilege – you have to believe that health is a right. Every person is entitled to living a healthy, happy life, free of disease and illness, free of disability, and free of pain. The unfortunate truth is that many people don’t live lives that way now and may never live that way. In my future practice as a doctor, I hope to work to ensure my patients have the best medical care with their optimized health always in my mind. I will value my patients as people with equality and integrity – no matter their race, background, income, homelessness, religious belief, or language barriers. I learned much more on my trip (like where the best pubs are in Ireland and where to get the best Americano in London) but of course this was the important, overarching theme that I wanted to write about first. I will forever be thankful for my travels abroad and hope to write of (perhaps more exciting?) experiences soon!

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London

I’m lying in my bed, with my windows open to the fresh, energetic air of London at night. I’m on Thoresby Street, living in Thoresby House, the yellow colored building with stairs that lead to the red door and a winding, wooden staircase that invites you into my hall. Perched in my bed, I hear the ripping of taxis and blustery honks, buzzing of motorcycles, and roaring of engines; but my favorite sounds so far have been the passing voices that find their way up and into my window. I’ve probably heard four different languages, fluidly speaking with ease and laughter and friendship as the passersby leave a trail of conversation. I can feel the wind blow in (the primary reason my window is open) and feel immersed in London already. I’ve been here for around 12 hours, I’ve been awake for around 34 hours, and I’ve already grown to cherish this city. I think of all the writers that I’ve read who have found inspiration in these streets, written of the exquisite beauty of the brisk walkers, the antiqued buildings, and the overcast skies. Virginia Woolf found London to be the only thing worth writing about – the true love of her life. Sherlock Holmes is one of the world’s favorite detectives (and certainly mine) because Arthur Conan Doyle’s medicine practice was unfortunately failing and writing was his escape. Winston Churchill echoed speeches that are inscribed in history books; and the royal family has been plagued by paparazzi since the establishment. And speaking of plagues – this city has seen them. I couldn’t wash my face and brush my teeth tonight without thinking of the cholera epidemic in London. Multiple diseases have ran rampant through this city and have faced eradication thanks to human intervention. Lots of things run through the old, regularly washed buildings of London. The streets taunt you with their secrets, the lives they have seen and the history that they’ve made. The buildings are beautiful – colored with character and stitched together with shades of red brick. And, oh, I’ve noticed – London is diverse. The people are colored many colors and speak many languages. Styles are different and some of the same. The university district was buzzing with students that held a sophisticated aura of intelligence and creativity. The people look different. They act different. They are different. Yet the real beauty I have found so far in London is that all of these differences are appreciated. Virginia Woolf would have been inspired by the many colors of faces she saw on the street and would have etched them out in unimaginable detail. London will charm you. I will lay here, with a Woolf-like awe, and observe with my ears the many sounds and feelings and emotions and thoughts that this sweet city will send up my window, to touch my heart and to move my hands to continue to write.

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finish line

You’ve got people in your corner. You may not know who they are yet, or maybe you do, but they are there. There are people out there that want to see you succeed as bad as you do. They support you, encourage you, market you to other professionals, love you in your flaws. They see your worth, even if you don’t. They recognize your talent, even when you don’t. Something about you inspires them, and you feed off their success and hunger for life. You have people that are your cheerleader. They rejoice with you when you do great things and they fall hard with you when you don’t. They are acutely aware of your life goals and dreams, and they can see what lights your eyes up and sets your heart ablaze mid-conversation. They tell you that they know what you were made for. They are happy for you. They are there for you. They are rooting for you. It may be your mom, teacher, co-worker, best friend, mentor, stranger, boss, dad, roommate, or just a passing face – but somehow they know you and believe in you. People are rooting for you. They don’t wish to see you fail, wish to see you find trouble, but are instead genuinely happy for you! These are true friends. Real friends that you find strength in. Friends that you reciprocate this feeling of pride, excitement, and overwhelming love for. Forget yourself and remember the people that are rooting for you. Those people will be the first people you hug whenever you cross the finish line.

-Me, to myself, when self doubt infiltrates my thoughts on the beautiful things God has given me.

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Pushing stones

Find something you think is important and spend your life supporting it. How does one find meaning in the mundane, spontaneity in the ordinary, and purpose in the routine? These are questions I think about often, and I don’t think anyone knows. But I do think some are closer than others. I read a book over Christmas break that impacted me deeply (I wrote about it on here), and what I took away from it was the basic human need to do meaningful work. Some would argue that life should be spent pursuing fantastical adventures, exploring the unknown, living robust and exciting lives…and while this is true to some extent, it is supremely unconventional and sometimes plainly unattainable. I am a person that sometimes gets carried away on these lofty, imaginative thoughts as well, but nonetheless I find my roots and become grounded in the practicality of life. So what do we do when we can’t spend our lives traveling the globe, jumping out of airplanes, investing in nonprofit organizations, saving the lives of homeless people, writing best-selling books? I think my personal answer was revealed to me by a classmate in my European literature class yesterday. We were discussing The Myth of Sisyphus by Albert Camus. While we didn’t read this piece, there was a metaphor that we discussed. This was the vision of someone pushing a rock, up a hill, only to never reach the top. This person spent his whole life, some would say ignorantly, pushing a stone up the hill to never become satisfied in his efforts. In a way, we spend our entire lives doing the same thing. Maybe we are pushing along many stones, exerting ourselves in unnecessary ways, only to find that the end was never our goal. The entire journey is about the stone. What does all of this metaphysical, philosophical jargon mean anyways? For me, really a practical person, it means finding a stone I think worthy of spending my life pushing. Identifying, consciously, what it means to do meaningful work. It means actively engaging in my life in ways that I have been gifted, and exploring the limits of those treasures. Viktor Frankl would say that our fundamental human condition rests on doing and performing meaningful, purposeful work. This may not be a traditional “job”, but instead a cause that we support, a belief we are rooted in, or a purpose we feel destined to fulfill. Or, it may be a traditional vocation where we can utilize and implore our skills, grow, change, and transform. For me, what my stone is becomes clearer every day. Admittedly, there will be (and are) doubts (why should I spend my time doing this anyways?) but whether we are aware of it or not, we are all pushing something. Maybe yours is social media, the opinions of others, and mediocrity. Maybe it is a watered-down version of yourself. Maybe it is what your family and friends want for you instead of what you want for yourself. It really only takes conscious knowledge to change these things, and I have found myself in these examples as well. We are all spending our time, energies, and lives supporting something. For me, I want to be a part of this process. I want to push a stone that allows me to transform lives through my curiosities and my skills. I want to spend my life pushing myself towards fulfilling a greater purpose than I could ever be. I want to care for people in their most vulnerable state, discover new ideas, advance our understanding of the human condition and the science behind it. I want to allow myself creative exploration and the ability to write when I want. I want to permeate love and kindness and grace and hope in the places I share with those I cherish. Simply, I want to dedicate myself and my time to something meaningful. I think everyone does. The important part is to find that thing that makes you light up inside and is worth your time and energy. We all have them, and we will spend all of our lives pushing, supporting, sacrificing, all that we have to navigate that stone up the hill towards what we consider a meaningful and promising life.

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Structured chaos

Life is busy. We are running around, chasing dreams that have us hooked like the bait on a hook, and life unravels its tightly woven, clean lines. I have found that peace and stillness lies within delighting each moment that leaves you feeling frazzled AND those that leave you feeling gratified. This is the busiest semester I have had at Belmont: everyday, I am waking early to study, running to class, popping into meetings, driving to the lab, spending hours doing research, then driving back late at night and finding I haven’t eaten in a while or gone to the gym for the day. So I take the time to eat, work out if I can, and talk with my roommates. Then I finish up studying/homework and find myself in bed usually past midnight and honestly wanting to watch some Netflix. There are some days that literally every half hour of my day is planned and inscribed in my planner. There are days were I have to be six different places within a few hours. This is not unique to me. My friends and classmates are equally as busy, running around doing their amazing things and chasing their dreams. We are all working so hard, always keeping in mind that elusive goal that we are chasing so fervently. It is one of the beautiful things about college, being surrounded by like-minded and motivated individuals. It is encouraging to see your friends doing awesome activities, getting accepted into awesome internships, and just all around being awesome. We are each carving our own unique pathway towards being who we want to become. I have two thoughts on this.

One. Remember that it is indeed your own pathway. Just because the person next to you is the President of twelve different clubs while running a nonprofit organization on the side doesn’t mean that you have to be that same person. The world works in harmony when there are many different types of people living their lives in uniquely different ways. While many of those I spend time around everyday have similar goals, I try to remember that we are all unique people and that individuality shouldn’t be compromised for the sake of achieving your dreams. If you have to forsake who you really are just to “make it”, I would reconsider what you are chasing after all. I find truth in cliches, and certainly “comparison is the thief of joy” is true to the end. Comparison is inevitable, but I have found that my happiness abounds whenever I remember that I don’t have to be like anyone else but who I am; I only have to be true to myself and my God. I admit that the courage to follow this is sometimes little, but I find it and hold onto it and hope that my life is incredibly robust because I am living out my dream not the dream of those around me. In short, don’t be afraid to take chances and be yourself when it seems the world (and our country) are increasingly trying to normalize the loss of individuality.

Two. Don’t let your to-do list run the roost! I am pointing this message directly at myself now because this is probably my biggest struggle. I make to-do lists every. single. day. Usually, I complete them and feel a grand sense of personal satisfaction. My lists keep me on track, organized, motivated, and determined. But when I step back and look at how completely structured my life is I remember that it’s really not supposed to be that way. Structure and routine are the fundamentals of my existence (or at least my mental health) but they evade the time for writing and reading and going out with friends and watching an episode of Netflix or going for a walk or visiting a new store or etc. etc. etc. So I am going to challenge myself to be more conscious of my to-do list and what it is potentially preventing me from experiencing that I need to experience (sometimes Netflix is simply not justifiable, but other things are). It is going to be beautiful this weekend and I have a laundry list of things on schedule. I am going to try to find the time to take it slow, to think, breathe, and meditate on the good things in my life that I am blessed to have and be able to do.

So I wish a very blessed Saturday for you all. Spend it doing what you love and don’t be ashamed of what that may be (full disclosure: I’ll be doing organic chemistry, possibly visiting TJ Maxx HomeGoods, and grabbing dinner with my friends or family). Enjoy it!

 

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