Aaron Llanso of Mission Bio On The 5 Things Everyone Needs To Know About Cancer

An Interview With Savio P. Clemente

Life goes on. — As we get better at treating and curing more and more cancer patients each year, we have a quickly growing population of survivors. Cancer survivorship is an important field that considers the psychological, financial, and long-term health ramifications for patients that have overcome a cancer diagnosis.

Cancer is a horrible and terrifying disease. There is so much great information out there, but sometimes it is very difficult to filter out the noise. What causes cancer? Can it be prevented? How do you detect it? What are the odds of survival today? What are the different forms of cancer? What are the best treatments? And what is the best way to support someone impacted by cancer?

In this interview series called, “5 Things Everyone Needs To Know About Cancer” we are talking to experts about cancer such as oncologists, researchers, and medical directors to address these questions. As a part of this interview series, I had the pleasure of interviewing Aaron Llanso.

Aaron Llanso has over 15 years of professional experience on all sides of cancer. He survived a blood cancer as a young adult, and has been a lab researcher, a biotechnology commercial leader, and an applications scientist. Aaron is currently Senior Director of Clinical Applications at Mission Bio, a company that has developed a method to learn about cancer resistance and relapse by examining DNA and characteristics of individual tumor cells. He is as determined as ever to translate novel clinical research and cutting-edge technologies to the clinic to improve clinical outcomes for all cancer patients.

Thank you so much for joining us in this interview series! Before we dive into the main focus of our interview, our readers would love to “get to know you” a bit better. Can you tell us a bit about your childhood backstory?

Sure! I was born and raised in Columbia, Maryland, and lived briefly in Houston, Texas, and Palm Harbor, Florida before returning to Maryland for middle and high school. I grew up playing many sports but have always loved ice hockey, which I still play today in a local adult league. My other pastimes include playing guitar, aggressive skating on ramps and in skateparks, sailing, and camping (I’m an Eagle Scout). I went to the University of Delaware, where I studied biology and Spanish. I met my wife in the first semester of college, and we have an amazing 4-year-old son, Reese, and a newborn daughter, Allison.

What or who inspired you to pursue your career? We’d love to hear the story.

My high school had a “tech-magnet” program, with STEM clusters focused on things like computer science, engineering, and biotechnology. I originally was interested in going the computer science route. I think it was my dad, though, that ultimately pushed me to go into biotech — perhaps it was an interest of his own he didn’t get to pursue professionally, or perhaps some good old-fashioned parental intuition! That was the first push.

Then, I had phenomenal biology teachers within the program. It was a unique practicum that included advanced laboratory coursework. The second year of the practicum was an internship placement which afforded me the opportunity to work at the National Cancer Institute in Bethesda, Maryland. I worked under a postdoc mentor, contributing to skin cancer research. It was an amazing and formative experience.

This is not easy work. What is your primary motivation and drive behind the work that you do?

One in three people will develop cancer in their lifetime; cancer touches everyone in one way or another. I’m incredibly fortunate to be alive 5 years after my own fight against lymphoma in 2016, to have regained my health, and started a family. It’s an incredibly fortunate exception to the unfortunate reality of most cancer diagnoses. Simply put, it’s an absolute privilege to contribute in any way to the cause. I’m laser-focused when it comes to the opportunity to work on the cutting edge of clinical research.

What are some of the most interesting or exciting projects you are working on now? How do you think that might help people?

I’m working hard to push single-cell multi-analyte technologies to clinical primetime, and here’s what that means. Cancer is so challenging to treat because it comes in so many different forms, and each changes so much over time, through both natural disease progression and in response to different therapies. Defeating cancer will require the right, specific response at the right time, and that will vary from patient to patient. Developing the right therapies, and knowing who needs what and when, takes tools that can look at both the contents of cancer cells and how they are behaving.

The tools I’m talking about read the sequence of a cell’s instruction books, typically through bulk approaches, which measure biomarker signals from biopsy samples that are ground up like fruit in a blender. This means the cellular context is lost, and the data generated represents the average signal across the thousands of cells — maybe your smoothie’s purple so you have a good idea there were strawberries and blueberries, but you taste something else in there that you can’t figure out.

What I work on is single-cell multi-omics, which is the novel ability to detect multiple data types from a sample while preserving the cellular context. In the smoothie analogy, now we can identify each fruit individually, find out there were a few rotten raspberries in the mix. This is a game-changer: for the first time, we can study dynamic disease biology at the resolution of individual cells, to understand how neighboring disease cells within the same tumor may behave differently from each other, in response to particular therapeutic strategies.

Cancer cells can have a sort of backup plan. If you interrupt some key process that had allowed them to flourish, many cells like that might die. But a small number may escape those early treatments, and once they spread they will not be susceptible to what worked before. The celebration of achieving “complete remission” too often is cut short by a relapse or recurrence. We’re using these single-cell studies to better understand how these cells responsible for relapse managed to persist and perhaps develop resistance to treatment.

I also spend a lot of time thinking about how we could one day detect and intercept disease pre-cursors before they develop into tumors. There’s a lot of buzz about this in the “liquid biopsy” field — which I believe is in its infancy, but holds immense promise for the future of precision medicine and early disease detection. The earlier we catch cancer, the more treatable and survival it can be. I’m dreaming of the day we can catch cells before they’ve even managed to transform into cancer. A Minority Report of clinical oncology, if you’ve seen the movie.

For the benefit of our readers, can you briefly let us know why you are an authority about the topic of Cancer?

There are several reasons I’m qualified to provide commentary and insight into the clinical oncology research market today: I’ve lived and breathed oncology research in various capacities over the last 15 years of my career. I’m a cancer survivor. I routinely partner with key opinion/thought leaders around the globe to advance new technologies and concepts, as well as to design proof-of-concept studies that have become both strategic commercial and clinical research programs with the goal of improving cancer outcomes.

Ok, thank you for all of that. Let’s now shift to the main focus of our interview. Let’s start with some basic definitions so that we are all on the same page. What is exactly cancer?

Cancer starts as a dysfunctional cell that has lost its ability to regulate the cell cycle. This can occur in any cell within the body. As the cancer cell begins to divide uncontrollably, it forms a tumor. This can be a focal lesion within solid tissue, or a liquid tumor within the blood or bone marrow. As tumor cells propagate, they can acquire additional mutations and evolve into an aggressive community of cancer cells that begin to wreak havoc on normal biological processes. Ultimately, this disruption and displacement of healthy cells will cause clinical symptoms that will typically progress towards a fatal outcome if left untreated.

What causes cancer?

Cancer begins as a result of certain changes in a cell’s DNA, such as mutations or other structural changes that causes the cell to lose its ability to regulate the cell cycle. This renders it immortal and capable of unchecked proliferation. There are many mechanisms that can lead to this outcome, and cancer is an umbrella term for a large number of subtypes. As the unchecked cell divisions form a tumor, it begins to crowd out healthy cell populations, ultimately disturbing normal biological processes and causing the patient to become symptomatically ill.

What is the difference between the different forms of cancer?

Cancer is generally defined by the tissue of origin, and by the genetic or phenotypic traits of the cancer cells as determined at diagnosis. Different forms of cancers have been shown to have different clinical courses and prognoses. Understanding the contents of those cells, and how that affects their behavior, is growing more important every day.

I know that the next few questions are huge topics, but we’d love to hear your thoughts regardless. How can cancer be prevented?

Huge topics indeed — I’ll do my best to be concise.

Our bodies are made up of tens of trillions of cells. Cancer can arise from any one of those cells. We each are genetic composites of our parents, and DNA profiles we’re born with represent truly unique starting points for each of us in terms of our inherited genetic risk for developing cancer. Then we acquire mutations in our daily life through a variety of mechanisms. Some mutations are simple replication errors; some are caused by lifestyle (like smoking, alcohol, and diet), environmental exposure (like UV radiation, ionizing radiation, chemicals and pollution), oncogenic viruses, and so on.

We’ve learned from pioneers like Peter Campbell that our bodies are incredible mosaics of cells that continually acquire mutations throughout our life as we age. As cells continue dividing, they pass those mutations on to the next generations of cells, and so accumulate increasing numbers of mutations over time. Where these mutations occur, and in what combinations, will determine the likelihood of progression to cancer.

So how do we attenuate this process? First, control the things we can control. And for the things we can’t, it’s important to follow medical guidelines for routine, preventative medical screens, as well as identify familial cancer history, and work with genetic counselors as appropriate to fine-tune one’s personal risk-reduction strategy.

How can one detect the main forms of cancer?

There’s a lot of obvious advice, but the key is consistent dedication to routine screenings, follow-ups, and communication with your doctors. Don’t ignore persistent, abnormal symptoms. Consistently follow through on all recommended routine medical screenings. Be aware of your familial cancer history, and talk to your doctor and a genetic counselor about your personal history, risks, and potential need for genetic profiling. Any unusual lumps, moles, or other physical concerns should be promptly shared with your doctor.

When I caught my cancer, I had been experiencing periodic but unexplained itching and drenching night sweats over several months. Ultimately, I found a 2 cm lump in my neck and went to my doctor.

Cancer used to almost be a death sentence, but it seems that it has changed today. What are the odds of surviving cancer today?

The odds of surviving cancer are entirely dependent on the type of cancer. Lots of cancers are very treatable — the best-case malignancies see survival rates better than 90%, which we measure as survival more than 5 years beyond therapy. Unfortunately, too many cancers are most often fatal — glioblastoma, pancreatic and triple negative breast cancer, to name a few. We’ve made tremendous progress in understanding the underlying biology of cancer, but it’s an incredibly complex fight against an enemy capable of clinical evolution, owed to the ability of tumor cells to mutate rapidly. There are many new and exciting therapeutic approaches that are enabling patients to live longer than ever before, and we are moving towards treating many cancers as chronic entities, though true cures are still elusive for the overwhelming majority of cancer types.

Can you share some of the new cutting-edge treatments for cancer that have recently emerged? What new cancer treatment innovations are you most excited to see come to fruition in the near future?

There have been several hot themes in novel oncology therapeutic strategies. First, small-molecule inhibitors targeting tumors bearing specific mutations have had a marked impact on survival and are often used in combination with older standard-of-care, such as chemotherapy and radiation. The immuno-oncology field has exploded in the last decade, with the 2018 Nobel Prize awarded to Drs. James Allison and Tasuku Honjo for their respective pioneering work that showed that the immune system can be harnessed to fight cancer. And now we are really seeing the cell and gene therapy field advancing rapidly. These are cutting-edge approaches that change human cells at a fundamental level: for example, engineering immune cells as living medicines to target cancer cells, or correcting DNA mutations in diseased cells to cure patients of their disease. There are distinct safety obstacles to navigate in these new treatments, but as the field and regulators tackle these issues, there is a bright future ahead full of game-changing treatment options for patients that have previously had no other options.

Healing usually takes place between doctor visits. What have you found to be most beneficial to assist a patient to heal?

Distraction and support. Normal social interactions often fall victim to circumstance. Friends who a patient may have routinely seen before their diagnosis may struggle with how to engage them, or with what to talk about or do with them, but the effort, companionship, and friendship is more important than the perfect idea. It always helps to get their mind off the elephant that never leaves their room, even if only for a brief visit.

From your experience, what are a few of the best ways to support a loved one, friend, or colleague who is impacted by cancer?

Their world gets turned upside down, so supportive gestures that may ease the burden of normal responsibilities at home. Consider if they have family that depends on them — young kids or elderly parents, for example — where you may be able to offer assistance. A home-cooked meal is always a welcome gesture for the supporting family, even if sometimes the patients themselves may not benefit, as unpredictable food aversions are common with chemotherapy. Keeping them company during treatment is sometimes an option, too, as sitting alone in a chemotherapy infusion room for hours on end can be understandably lonely and depressing. I was so fortunate to have a family member by my side during every infusion to make conversation, and to not feel alone through a scary process.

What are a few of the biggest misconceptions and myths out there about fighting cancer that you would like to dispel?

One myth that always bothers me is the conspiracy theory that “big pharma” is more interested in selling drugs that treat cancer patients long-term than curing them of their disease. I’ve worked closely with scientists at most of the large pharmaceutical companies as well as key opinion leaders within the leading academic medical centers around the world: this is simply not true. Cancer is an umbrella of complex diseases that the field at large is working hard to better understand and treat. Developing better therapies that safely and effectively cure patients is unquestionably everyone’s goal.

Breakthrough discoveries are happening faster than ever before, thanks to novel technology development. Next-generation sequencing is an excellent example of a force multiplier that dramatically accelerated the pace of scientific understanding of the genetic basis of cancer. Now we are delving into single-cell resolution that is enabling scientists to understand disease evolution at the single unit of biology: the cell. I’ve never once come across a scientist in my entire career that was interested in the profitability of a drug compound instead of its ability to eliminate disease and cure a fellow human.

Another important myth is that clinical trials are simply high-risk engagements that only serve to make the patient a “guinea-pig” for the pharmaceutical company. In fact, clinical trials are highly regulated processes that require extensive ethics and safety reviews of trial design before a patient is ever treated with an experimental drug. Clinical trials often represent the best possible treatment options for cancer patients that may have few other — if any — options left, and there are often breakthrough clinical outcomes demonstrated in these scenarios. It’s important to remember that any clinical trial is preceded by a mountain of pre-clinical research data that strongly suggests utility and efficacy beyond that of current standards of care.

Thank you so much for all of that. Here is the main question of our interview. Based on your experiences and knowledge, what are your “5 Things Everyone Needs To Know About Cancer? Please share a story or example for each.

1. Many cancers are preventable.

In my work, I spend a lot of time thinking about how we could one day detect and then intercept cancer precursors before they develop into tumors, and I hope to materially contribute to those discoveries. Today, we know that some cancers are hereditary, meaning there are genetic traits inherited from one or both parents that may predispose someone to a particular type of cancer. However, many cancers are actually preventable through healthy lifestyle choices and mitigation of environmental exposures, as these things can lead to acquisition of mutations as we age and as a function of the things we do or consume throughout our life. And these things can increase our risk of developing cancer.

For example, the use of tobacco and alcohol is associated with increased risks for many different types of cancers, while UV radiation from direct sun exposure can increase the risk of developing skin cancers such as melanoma.

Similarly, poor diet, lack of physical activity, and obesity can all increase risk of colorectal cancer, among other health concerns. Environmental exposures such as pollution, radiation, or chemicals are also important factors in lung cancers, lymphomas, thyroid cancer, and so on. Finally, some infectious agents can lead to cancer — a great example of this is the human papilloma virus (HPV), which can lead to cervical, anal, or oral cancers among others. Fortunately, in the case of HPV, there is a highly effective vaccine!

2. Cancer is most treatable when it is caught early.

The sooner a cancer is detected, the higher the likelihood that it can be successfully treated. Listen to your body. Cancer screening tests are still being developed for broad use in the general population to catch disease early. And there’s been a lot of exciting acceleration in that field. In the meantime, it’s very important to understand your family’s history of disease, and based on this information, follow all preventative measures recommended by your doctor. Go to your routine appointments, and follow up on all preventative screening tests at the recommended ages. This includes skin checks for changing moles, colonoscopies, mammograms, annual blood work, and so on. Above all, know your body and communicate with your doctor — be vigilant and report anything suspicious or any changes in your body. I was 29 years old when I found a 2 cm lump in my neck. I had experienced periodic itchiness and night sweats, but never thought it could be tied to cancer. By the time I saw a doctor and had a biopsy, it was stage 2 lymphoma, which fortunately is still considered early stage. I was very lucky to have found the lump and quickly followed up on it with my doctor before it spread further and became more difficult to treat.

3. Get multiple opinions, and at least one from an academic medical center.

The cancer treatment landscape is evolving rapidly and so much progress has been made in the last decade, but the reality is there’s no one-size-fits all treatment approach. In many cancers, the field has begun to move from blanket chemotherapy and radiation strategies to non-chemo-based therapies, including new immunotherapies that enlist the body’s own immune system in the fight against a tumor.

There’s also targeted treatment options that home in on particular tumor mutations that we can elucidate by sequencing, and scientists are now even engineering immune cells for infusion into the body to find and fight cancer cells — this is a field we’re directly supporting through our work at Mission Bio, it’s a very exciting space.

Because advances are happening so often today, it’s important to include an opinion from a doctor at an NCI-designated academic cancer center. These are the premier institutions where you will find cutting-edge clinical trial options, and are more likely to have your particular case reviewed by a tumor board, which is a panel that’s composed of multidisciplinary doctors that aim to leverage their collective “hive-mind” to chart the best treatment options for a patient.

4. You are your best advocate. Understand your treatment options.

Treatment decisions are often complex and there may be multiple options in front of you depending on the stage, and they’re each going to entail distinct benefits and drawbacks. Cancer is not routine, and treatments are not one-size-fits-all.

It’s particularly tricky if a biopsy is inconclusive, or if a scan is unclear. One treatment approach might be “more aggressive” but portend higher risk of lifelong side effects. Another option may be easier to tolerate with fewer side effects, but perhaps carries a lower chance of success, or a higher risk of disease progression or relapse. Weighing the pros and cons is rarely a straightforward exercise, and ultimately comes down to the patient’s decision — so please ask questions and be informed about your situation.

After I completed chemotherapy for lymphoma, all of my doctors agreed that I needed radiation, but they disagreed on the type of radiation. Ultimately, I pursued multiple doctor opinions across multiple institutions, found a tie-breaker, and made my decision after carefully understanding each of their rationales. This requires a lot of effort and dedication, but ultimately no one will push as hard for the right answer for you, as you will for yourself.

5. Life goes on.

As we get better at treating and curing more and more cancer patients each year, we have a quickly growing population of survivors. Cancer survivorship is an important field that considers the psychological, financial, and long-term health ramifications for patients that have overcome a cancer diagnosis.

One of the most challenging aspects of survivorship for me was grasping the fact that life goes on. It’s often an unspoken mental challenge to recover from facing a potentially terminal diagnosis and then trying to transition back to feeling normal again.

I was always concerned with what big life decisions could be harshly impacted by the potential of relapse, which never really leaves the mind. As a young adult, for me this meant questions like “can or should I start a family?” “Does it make sense to buy a house?” “Should I prioritize advancement in my career now?” These can be tough questions and psychological experiences, and it can feel lonely and stressful when facing the uncertain in life.

Looking back over the years since my own diagnosis, I reflect on how much I struggled with wanting to start a family, but weighing the risks of what were to happen to my family if I fell ill again. Or for example, wanting to buy our home, but fearing financial impact if I faced further rounds of treatment and couldn’t work. It was really learning to balance the fear of taking steps forward in spite of the risk of falling back.

Ultimately, regardless of a medical outcome, life doesn’t stop, and I believe everyone, especially cancer survivors, should get busy living your life — while always hoping for the best outcome. But it’s important to say that cancer survivors are never alone, and it’s important to reach out to support groups, fellow survivors, or professionals if you do experience the diverse challenges of survivorship. It’s always easier said than done, but I sincerely hope it’s helpful advice or needed encouragement from the perspective of a survivor.

You are a person of great influence. If you could start a movement that would bring the most amount of good to the most amount of people, what would that be? You never know what your idea can trigger. :-)

I’m a big believer in routine, non-invasive screening approaches that can be done annually at a PCP office. Technologies are not quite as good as they should be for this purpose today, but I am excited and optimistic for what’s on the horizon in this fast moving field!

How can our readers further follow your work online?

Twitter: @aaronllanso

LinkedIn: https://www.linkedin.com/in/aaronllanso/

www.missionbio.com

Thank you so much for these insights! This was very inspirational and we wish you continued success in your great work.