C3 Magazine: Summer 2020 Edition

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TO LIVE 04: CANCER RESEARCH DURING COVID-19 12: Q&A WITH CECILIA CAINO, PHD 13: C3 MD RYAN WEIGHT, DO, MS 14: ART SHAPES STAGE IV FIGHT 18: WILL VAPING REVERSE A MIRACLE 22: OVARIAN CANCER RESEARCH FUNDED

UNIVERSITY OF COLORADO ANSCHUTZ MEDICAL CAMPUS

N WS Christopher Lieu, MD, named CU Cancer Center Associate Director of Clinical Research University of Colorado Cancer Center is excited to announce that Christopher Lieu, MD, is now the Associate Director of Clinical Research. Lieu, who is also the director of the Gastrointestinal Medical Oncology Program, joined the CU School of Medicine faculty in 2011. For the past nine years, Lieu has been an investigator on numerous CU Cancer Center clinical trials, including taking the lead on early-onset colorectal cancer research.

Lieu received the National Cancer Institute Cancer Clinical Investigator Team Leadership Award in 2017.

Additionally, Lieu is the Vice-Chair of the National Cancer Institute Colon Cancer Task Force and sits on the National Comprehensive Cancer Network Panel for Neuroendocrine Cancers.

“Dr. Lieu has been an invaluable part of the cancer center since the start,” says Richard Schulick, MD, MBA, Director of the CU Cancer Center and Chair of the CU School of Medicine Department of Surgery. “I speak on behalf of the entire faculty when I say that I am thrilled to have him as the AD of clinical research.”

C H R IST OPH E R L IE U , M D

“The reason why there are so many of us that choose academic medicine is that we want to be part of changing our field and improving the lives of our patients and their caregivers.”

- Dr. Chris Lieu

“I believe our cancer center is in a very exciting phase of growth and investment,” says Lieu.

“There is so much talent, skill and expertise that exists on this campus, and I hope to be able to provide our incredible researchers with the ability to conduct outstanding clinical investigations that change our patients’ lives and puts our cancer center and university into even greater national prominence.”

In new role at CU, Jamie Studts works to reduce stigma blocking use of lung cancer screening As recently appointed co-leader of the CU Cancer Center Cancer Prevention & Control Program, Jamie Studts, PhD, will help Colorado and the rest of the country implement nationwide lung cancer screening. The United States Preventative Service Task Force recommends lung cancer screening for people 55-80 years old who have a 30 pack-year history of smoking (each pack-year is 20 cigarettes smoked every day for a year). However, the National Cancer Institute found that only 5.9% of people in this high-risk group actually receive the recommended screening. At CU Cancer Center, Studts will be working with ongoing projects by researchers including Cathy Bradley, PhD, and Russel Glasgow, PhD, to understand the barriers that keep high-risk individuals from completing this recommended lung cancer screening.

J AMI E STUDTS, PHD

Get more CU Cancer Center news on our blog: w w w. c o l o r a d o c a n c e r b l o g s . o rg Subscribe for updates on the latest research, news and events.

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PROMISING outreach

University of Color ado Cancer Center adds years back to bile duct cancer patient’s life When Lydia Mallernee was diagnosed with cancer in March 2018,

Fewer kids enrolling in pediatric cancer clinical trials Historically, pediatric cancer patients have been much more likely than adult cancer patients to enroll in clinical trials as part of their treatment.

Now a study by University of Colorado Cancer Center researchers working at Children’s Hospital Colorado shows pediatric oncology clinical trial enrollment may be down, from 40-70% seen in studies completed in the 1990s, to 20-25% in the early 2000s, to 19.9% in the current study.

“The potential reduction in enrollment isn’t all bad news,” says Kelly Faulk, MD, CU Cancer Center investigator and pediatric oncologist at Children’s Hospital Colorado. “One reason trial enrollment may be decreasing is that good treatments have been developed for some of the most common childhood cancers, shifting the focus and resources toward opening trials for higher risk, but often more rare cancers.”

she didn’t want to know

However, the study does reveal a group of cancer patients that has historically and continues to under-enroll in clinical trials, namely adolescent and young adult (AYA) patients from ages 15 - 29.

the prognosis.

“I didn’t care what the prognosis was,” Lydia says. “I was not going to stop fighting my cancer.”

LY D IA M A L L ER N EE The fact was, with metastatic cholangiocarcinoma, or advanced cancer of the bile duct, Lydia was likely to live only two- to eight-months. In fact, after she collapsed while walking to the bathroom while admitted to her community hospital, it looked like Lydia might not make it out of surgery.

“They can feel lost between pediatric and adult cancer care, and unfortunately these AYA patients represent a population that has failed to see the same improvements in outcomes that their younger counterparts have,” Faulk says.

“Lydia was declared a code blue,” says her husband, Mike.

“Tons of doctors came to her room and she was rushed to surgery. It turned out she had three embolisms in her liver. During the surgery her heart stopped, and they had to resuscitate her again.”

Lydia survived and eventually they discovered that her tumor had a special feature called “microsatellite instability,” which meant it had a good chance of responding to immunotherapy.

That’s when Lydia came to University of Colorado Cancer Center, where Alexis Leal, MD, took over her care.

“We switched her to pembrolizumab, an IV immunotherapy given once every 3 weeks,” says Leal. “And she has been on it since February of 2019 with good response and minimal negative impact on her quality of life!”

Lydia has been NED, or no evidence of disease, since

Color ado study overturns ‘snapshot’ model of cell cycle in use since 1974 Cells have a big decision: Should they replicate or sleep? Healthy cells can go either way. Cancer cells’ replication switches are stuck in the ‘on’ position.

Since 1974, scientists have thought that cells make this go/no-go decision based on a snapshot of their surroundings.

Now a study by the lab of Sabrina Spencer, PhD, University of Colorado Cancer Center investigator and assistant professor in the CU Boulder Department Biochemistry, together with lead author Mingwei Min, PhD, postdoctoral fellow in Spencer’s lab, shows that it’s more like a movie.

SABRI NA SPENCER, PHD

August 2019.

“In 2018, I was given just months to live. Now, you would never know I had cancer,” says Lydia. “The only way I can explain it is a miracle.”

“Since the environment is continuously fluctuating, it makes sense that cells would continuously sense their surroundings throughout the cell cycle to enable them to adapt appropriately,” Spencer says.

“Understanding when cells care about growth signals, and when cells are sensitive to drugs that block these signals, can fine tune how people utilize those drugs.”

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CANCER RESEARCH

IN THE TIME OF COVID-19 As doctors care for patients and some cancer labs take on COVID-19 research, for others it’s life on hold

By Garth Sundem

January 2020 was unseasonably warm and dry, so pleasant that students on the Anschutz Medical Campus ate lunch at picnic tables and scientists emerged confused and squinting from hibernation in the campus research buildings. One person who was not there was Deguang Kong, visiting graduate student in the lab of Heide Ford, PhD, University of Colorado (CU) Cancer Center Associate Director for Basic Research. With his PhD work wrapping up, Deguang had taken a quick leave to interview for jobs near his home…in Wuhan, China.

February came and volunteers in hazmat suits were spraying the streets of Wuhan for coronavirus. Deguang never made it back from China. Via teleconference, he taught lab member Connor Hughes how to take over his mouse experiments, and he told his roommate Hengbo Zhou, who was also finishing PhD work in the Ford lab, to get ready to defend his dissertation virtually.

“When Hengbo told me he had to get ready to defend virtually, I said ‘don’t be so melodramatic.’ He said we had to watch it, but I couldn’t imagine everything would be shut down here,” says Ford.

A few weeks later his predictions were right, everything shut down here.

H E ID E F OR D , PH D

Meanwhile in Boulder On Thursday, March 12, CU Boulder researcher and CU Cancer Center member Sabrina Spencer, PhD, spent the better part of her undergraduate biochemistry lecture discussing how they would be continuing the class online. After the weekend, students wouldn’t be coming back. At the end of the lecture, her students applauded.

started recommending to my lab to do all possible experiments first and save the analysis for later. Telling people to cram in six experiments without analysis isn’t normally how you would do science, but I was worried labs would shut down. Now, at least people in my lab have stockpiled data. However, we’re not going to last on that forever.

Maybe another two months?”

Two months was exactly what she needed. In May the labs across campuses started to open back up for research with heightened precautions such as social distancing and mask wearing, but being open is a great step in the right direction for research.

enrollment of patients on clinical trials that test promising new therapies.

“The pandemic has pushed down clinical trial enrollment,” says Schulick.

“Some of these clinical trials are going to be positive and when enrollment is down, we may be losing the opportunity to help patients.”

As CU Cancer Center Associate Director for Clinical Research, no one knows this better than Christopher Lieu, MD.

Lost Time “We’re going to lose time and in cancer, time means lives,” says CU Cancer Center Director, Richard Schulick, MD, SA B R IN A SPE N C E R , PH D

“It was surprisingly emotional,” Spencer says. “They were kind of saying goodbye. It just felt like the end of an era – like our lives would be really different after today.”

But by that point, Spencer had spent a month preparing her lab for remote work. The Spencer lab uses cuttingedge technologies to watch single, live cells go about their business. Much of her lab’s cancer work is computational – they gather terabytes of data with nifty microscopes, but then it takes time to crunch the numbers to see what they found.

“I’ve been worried about this virus since early January,” Spencer says. “Despite being called Chicken Little by family, I

CHRI STO PHER LI EU, MD

“If a clinical trial is not deemed critical to survival, those trials are on pause. But unlike some other areas of medicine, cancer clinical trials may be keeping our patients alive,” Lieu says.

RICHARD SCHULICK, MD, MBA

MBA. Part of this lost time might be delays in basic research that push back the development of new treatments. But the more immediate effect of COVID-19 is on current patients, especially the

However, cancer patients are almost universally immunocompromised, whether from the disease itself or from treatments like chemotherapy, radiation and surgery. For these patients, catching COVID-19 could very well be fatal and visiting a hospital with an influx of COVID-19 patients is imperfect, to say the least. Still, cancer doesn’t care about a pandemic and patients still need treatment.

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“In some cases, the benefits outweigh the risks,” Lieu says. “The idea is striking a balance between not harming someone by withholding care, but also not needlessly increasing exposure.”

Some trials even remained open for new enrollment. “To put a new patient on trial, it has to be a very critical situation right now, but those situations exist in cancer,” Lieu says.

“Leadership on our campus is doing a great job weighing the various risks and benefits of how we provide cancer care, and working together to find the right balance,” says Schulick. As for new clinical trials, themselves, “We’re thinking about new trials, but we can’t start them,” he says. “It’s like designing a car but not being able to build it – only a million times more important.”

Cancer Research Insights into COVID-19 Along with Heide Ford, Sabrina Spencer, and the vast majority of other researchers on campus, Joaquin Espinosa, PhD, shut down his lab in March. He works with the biology of how cells “talk” to each other, primarily focusing on cancers and Down syndrome.

One of the major complications of COVID-19 is the overactive immune system of cytokine storm, a cascade of immune activity that attacks a patient’s body and can become even more dangerous than the virus itself.

JOA QUI N ES PIN OSA , PH D

“All these years we’ve been exploring immune dysregulation in Down syndrome. It’s like people with Down have a cytokine storm every day,” Espinosa says.

With the revelation that the drug being tested in Espinosa’s clinical trial against Down syndrome- associated alopecia may also short-circuit cytokine storm in COVID-19, it didn’t take long to get permission to re-open his lab. Espinosa’s lab is working with an international consortium of investigators testing this drug class in COVID-19 patients while also studying these drugs in animal models of lethal cytokine storms.

The lab of CU Cancer Center investigator, Jennifer Richer, PhD, is also using the tools of cancer research to explore COVID-19.

Much of Richer’s recent cancer research has examined the role of androgen (testosterone) receptors. We think of androgen driving prostate cancer, but Richer’s work shows that in addition to hormones like estrogen and progesterone, androgens can drive breast cancers, particularly those resistant to traditional estrogen-blocking therapies. In a fascinating twist, scientists have

JENNI FER RI C H E R , PH D

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shown that the “receptors” cells use to grab androgen also control proteins that help viruses enter lung cells.

According to Richer, this dependence of viruses on androgen could partially explain why men, who have much higher levels of testosterone than women, are at higher risk of COVID-19 complications. It could also explain why most pediatric cases happen near the onset of puberty.

“That’s one of the things I’ve been doing – seeing what we know already from our work on how breast cancer spreads to the lung that is applicable to viral infections,” Richer says.

In addition to finishing grants and papers on breast cancer, including a major American Cancer Society Institutional Research Grant renewal that funds many of the Cancer Center’s junior faculty, Richer is partnering with CU infectious disease specialist Mario Santiago, PhD, to further explore this crossover between

androgen-driven cancers and viral infection at the basic science level.

One question is how easy it will be to pivot back to cancer research once the pandemic ends, or if funding for cancer research will be permanently reprioritized to study infectious disease.

“COVID research is of immediate importance, but cancer research is still important, too – cancer is not going away,” Richer says.

“It’s like ice,” says Lieu, “a quick freeze and a slow thaw to carefully and safely reopen the hospital services, basic science and clinical research. It’s not easy to restart everything and in some ways getting back up to speed is more complex than the closing. The ramifications of that will be seen much longer than anything else.”

That said, CU researchers also find reasons to be hopeful for science, scientists and most of all our patients.

CU researchers also find reasons to be hopeful for science, scientists and most of all our patients.

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“Having the time to think about your projects – that downtime can really be valuable. It can give you the headspace to think about something in a new way and reevaluate your approach.”

Silver Linings “We can rethink things, analyze data every which way to see if it’s telling us things we hadn’t seen before,” says Richer. “Having the time to think about your projects – that downtime can really be valuable. It can give you the headspace to think about something in a new way and reevaluate your approach.”

According to Richer, the time to step back and think may lead to new, creative ideas emerging from the pandemic.

“My lab is getting way more thinking time,” agrees Spencer. “They’re reading all the papers they never had time for when they were focused on experimental work.”

And, “With all this work, I think the public and government really understand how important health care research and discovery is,” says Schulick.

According to Schulick, COVID-19 has also helped doctors and researchers learn new ways of communicating and delivering care that may have benefits long after the pandemic ends.

“Overnight, we’ve learned how to do things remotely. I’m seeing patients from very remote places and it’s almost as good as if they had driven 10 hours, stayed in a hotel, saw me for a short appointment, and then drove back 10 hours,” Schulick says.

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On the Other Hand…

“Some people are having more focus time, but there’s also a lot lost,” says Ford. “Now we’re six weeks in and at this point, we’re getting diminishing returns from taking time off to think, and it’s time to get back to doing. People are itching to get back into the lab.”

One of these people is Ford’s graduate student, Jessica Hsu. “I spent a year optimizing the protocol for the experiment and we had just gotten to the point in March where I was comfortable getting started,” she says. Not only was this experiment the last piece of her PhD project, but it was an important part of the Ford lab’s major grant proposal.

“That’s when the discussion of our lab being shut down came about,” Hsu says. “And then it happened.”

Still, there was a chance they could save the experiment.

“Heide forfeited her own access to the lab to have me give me that space,” Hsu says. As her other ‘essential’ lab member, Ford chose Connor Hughes to continue Deguang’s experiments with mice, which J E SSIC A H SU

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“

But just as cancer doesn’t stop for a pandemic, researchers and doctors who work with cancer can’t stop for the pandemic, either.

W E CON TINUE MOV ING

FORWA R D.

were nearly done and which would take six months or more to restart if paused.

“As much as I want to finish my project, I know we can’t rush back to the labs. We’re all taking the precautions needed to come back as seriously as we took the precautions to shut down,” she says.

Until that happens, Hsu will be stuck with a blank space in her PhD manuscript. In the meantime, Deguang will not be able to return from China.

Hengbo successfully defended his PhD virtually.

Hughes remained essential long enough to complete Deguang’s mouse experiments. Ford has been arranging socially distanced dog walks with colleagues where they talk about what it will look like to get back to work. Lieu and Schulick continue to take care of cancer patients. Spencer is crossing her fingers that it won’t be long before her team can

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get back into the lab safely. And Richer and Espinosa are doing what they’ve always done: Science meant to save lives.

Like the rest of our world, cancer research has been forced to adapt, and like everywhere it has been imperfect. But research and researchers are resilient.

“This is definitely a speed bump and we will need significant support to get back up to speed,” Schulick says. “But just as cancer doesn’t stop for a pandemic, researchers and doctors who work with cancer can’t stop for the pandemic, either. We continue moving forward. We are still taking care of patients. We are still making progress. And when all this is over, I think we’ll all see how strong and committed our community is to continuing the fight against cancer.”

DEC

DING CANCER

University of Colorado Cancer Center hosts the multi-million-dollar technologies needed for cancer research in “Shared Resources” for use by our members and, for a higher cost, by the Colorado and regional research communities. But cancer research isn’t the only use of these advanced science tools. During the COVID-19 pandemic, the CU Cancer Center Shared Resources have been turning their technologies to the study of the virus. Here just a few of the ways they’ve been helping understand, diagnose, treat and prevent coronavirus:

Cell Technologies Shared Resource (CTSR)

Mass Spectrometry Shared Resource (MSSR)

COVID-19 antibody tests require COVID-19 proteins, and the CTSR can make them. Because the CTSR is unique in the region, the lab may deliver COVID-19 proteins needed for serum antibody testing not only to the Colorado community, but also to Wyoming, Montana, and potentially other states as well.

One of the major complications of severe COVID-19 is blood clots in the lungs – a pulmonary embolism that can block lung function leading to death. But which coronavirus patients are developing these clots? The MSSR is powering a search for metabolic and protein signatures that can act as early warning signs of these dangerous embolisms.

Animal Imaging Shared Resource (AISR)

Human Immune Monitoring Shared Resource (HIMSR)

AISR is one of the few labs to remain open during the pandemic and has been using animal models to learn how to image important features of COVID-19 in human patients.

Now imaging techniques developed in the lab are being moved to the clinic to visualize kidney function and systemic inflammation in COVID-19 patients.

You’ve heard of the Human Genome Project. Now the HIMSR is partnering with the Cancer Center Tissue Biobanking and Histology Shared Resource to store COVID19 samples for individual research efforts and for a major project known as the COVID-ome.

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A CONVERSATION WITH CECILIA CAINO, PHD CU Cancer Center Mentored Member Associate Professor, CU School of Medicine

BY JESSICA CORDOVA

Department of Pharmacology

Cecilia Caino has been researching cancer cell biology at University of Colorado Cancer Center since 2017. Cecilia earned her PhD in Cellular Biology from the University of Buenos Aires with her research component performed at the University of Pennsylvania, and completed a postdoctoral fellowship at The Wistar Institute. We spoke with Dr. Caino about her research on how cancer cells use energy and how their unique energy strategies could help cancer cells spread.

C3: What excites you most about your research?

mitochondrion can travel to different

Caino: I am a cell biologist at heart and I am

or split into daughter mitochondria. We

curious to understand how and why cancer

also see that mitochondria work with other

exploits structures called mitochondria for

structures inside our cells to promote cell

energy resources that allow cancer cells to

fitness. These processes help healthy

spread and resist therapy. When you look at

cells resist stress and adapt to changing

cells under the microscope, it is fascinating

environmental conditions. In cancer,

to see the constant dance of mitochondria,

reprogramming of mitochondrial dynamics

rushing about the cell and undergoing “kiss

helps cancer cells spread and resist therapy.

locations, fuse to another mitochondrion,

and go” cycles of fusion/division.

Caino: Recently, we have learned that

C3: What convinced you that University of Colorado Cancer Center would be the best place to work on mitochondria research?

mitochondria don’t just stay in one place

Caino: Much of what we know about

C3: What is the biggest breakthrough so far in your research?

making energy. Instead, they use something

mitochondrial dynamics was discovered

Caino: We showed that cancer cells

called “mitochondrial dynamics,” which

in neurons, and we still have only limited

reprogram mitochondria to meet local

is the focus of my research: an individual

knowledge of how they are wired in cancer.

demands for energy. Cancer exploits regional

There are no drugs to target most of the

control of mitochondrial function, powering

processes of mitochondrial dynamics, and

up mechanisms of invasion and metastasis.

C3: So how do cancer cells manipulate mitochondria?

we don’t know what functions are crucial

Pharmacology, I have access to outstanding

C3: What type of cancers will benefit the most from this research?

collaborators and unparalleled resources to

Caino: We have evidence that mitochondrial

tackle some of these questions from basic

dynamics are dysregulated during metastasis

cancer research, cell biology, structural

of cancers including those of the prostate,

biology and pharmacological angles.

breast, skin and brain. In animal models,

in cancer. As a Mentored Member of the CU Cancer Center and the Department of

we were able to block or reduce the spread

C3: How will your research impact the treatments being provided to cancer patients?

of prostate cancer and melanoma by

Caino: Our research is basic. We aim

differences between normal and cancer cells

to identify how mitochondrial dynamics

because this opens opportunities to target

fuel metastasis. In the long term, this

these differences in cancer cells and limit

understanding may lead to drugs that can

their metastatic potential.

prevent or reduce cancer’s ability to spread.

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manipulating key players of mitochondrial dynamics. It is truly exciting to find

The Human Touch

MD

CLINICAL

CARE

RYA N W E IG HT M OVE S F R OM BENCH TO BE D S I DE TO C ARE F OR PATI EN TS

BY TAYLO R A BA RCA University of Colorado Cancer Center member

it would be in a lab. He studied biomedical

Ryan Weight, DO, MS, has always been

engineering and was well underway with research

passionate about caring for patients. However, in

when a project changed his trajectory.

early April, in the middle of a global pandemic, the way he goes about patient care looks a little different.

“COVID-19 has changed the way I practice

“I was working on a way to detect

“I believe this pandemic will change the way medicine is practiced all over the world.”

medicine significantly,”

circulating melanoma cells in the blood stream, which included working closely with surgical oncologists,” Weight explains. “It was then that I fell in love with the field. I loved the compassion and

Weight says. “I only see patients in the clinic

personalized interaction that came with treating

whose life depends on treatment. Most of my

patients. I made the tough decision to leave

appointments are done via Telehealth.”

research to practice medicine with the intent to

Like most people living in the United States, and

become an oncologist.”

around the world for that matter, Weight is doing

Although Weight graduated with an DO rather than

much of his daily work remotely. Unlike most

a PhD, he still holds a special place in his heart for

people, his work can be a matter of life and death.

research. The topic of research that inspires him

“The pandemic has brought a number of

most? Immunotherapy.

challenges that we, as providers, have never had

“Immunotherapy is rapidly expanding in the

to deal with before,” he says. “Now we have to

medical field, and especially in cancer,” he says.

weigh the risks versus benefits of treating people

“Just a few years ago there were only a couple

with chemotherapy or other immunosuppressive

FDA approved indications for immunotherapy

treatments, or even look at postponing treatments

medications. Now we are seeing the indications

to reduce the risk of infection. It’s incredibly

increase substantially across different tumor types.

difficult. There is not much data about the impacts

Immunotherapy is a different way to approach

of delaying treatment, so it is hard to say how

cancer by harnessing the innate immune system

this might impact survival. It is an extremely

to treat the disease.”

challenging time for not only me, but the entire health care system.”

But just as anything new can come with unforeseen surprises, immunotherapy sometimes

At the start of his career, Weight knew he wanted

has unexpected side-effects for a small number

to work in health care, but always imagined

of patients. Because of this, Weight helped

RYAN WEIGHT, DO, MS developed an immune-related adverse event (irAE) response team in his previous clinic and hopes to see it soon on our campus.

“I helped create one of the first response teams before national guidelines were created,” he explains.

“As the use of immunotherapy is increasing, providers are also having to manage an increasing number of adverse reactions related to the drugs.

Because of this, it is important to have a specialized team that has an interest in how the immune system interacts with healthy organs in the body.”

Immune-related adverse response teams are not available at every cancer clinic, however as the use of these treatments expands, Weight sees hope for virtual consultation teams that could extend the reach of this expertise.

“Virtual toxicity teams would be incredibly helpful for physicians and patients alike,” says Weight.

“Educating patients and providers on how to respond to negative side-effects of immunotherapy could save lives across the United States.”

While ‘virtual care’ may be the next big thing in medicine, Weight is looking forward to the day he can see patients in the clinic once again.

“I believe this pandemic will change the way medicine is practiced all over the world. Telemedicine will be used more frequently, which is amazing when it comes to accessibility and expanding care,” he says.

“That being said, I am ready to talk, laugh and care for my patients in person. No amount of phone calls or Zoom conferences can replace the human touch if practicing medicine.”

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At that point, Shelley had a 3% chance of being alive five years later.

Then her doctors found another option: The immunotherapy nivolumab (Opdivo) had recently earned FDA approval to treat melanoma and small cell lung cancer, and in November 2015, it was approved for kidney cancer. Shelley’s doctors were able to talk her insurance company into letting her be one of the first patients to use the drug outside clinical trial testing.

The treatment wasn’t easy. Immunotherapy helps a patient’s immune system “see” cancer, but it can make the immune system attack healthy tissue, too, leading to side effects. In Shelley’s case, it meant inflamed joints that made movement painful. Still, seven infusions later, her cancer had stopped growing and Shelley was determined to get back to her life.

And for her, life means art.

TO LIVE

ARTIST SHELLEY KERR’S SCULPTURES EXPLORE THE BATTLE, JOURNEY, AND GRATITUDE OF FIVE YEARS WITH STAGE IV CANCER

BY GARTH SUNDEM “Have you ever had a dream when you wake up and everything is just kind of vibrating? It doesn’t make any sense but it kind of points the way?” asks Fort Collins artist and musician, Shelley Kerr.

In fall 2019, after living with stage IV cancer for five years, Shelley dreamt about the Seven Sisters of the Pleiades. The importance of this dream shifted her focus from the battle to the journey her cancer had led her on.

“Doctors didn’t use the word ‘terminal,’ but I knew what they meant,” Shelley remembers when talking about first being diagnosed.

In 2014, at age 59, Shelley was diagnosed with kidney cancer that had metastasized (spread) to her bladder and even after surgery and intensive chemotherapy at University of Minnesota, near where she was living at the time, “I still had a tumor the size of a ping pong ball, and it was bleeding,” she says.

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TO LIVE “How do you represent cancer?” Shelley asks.

“I went through a few iterations in my mind and thought about the Greek language – much of the medicine I used was invented in the Greek tradition.” Shelley’s nephew is an academic studying Ancient Greece and started sending Shelley words and letters. Eventually she settled on a sculpture influenced by characters of the ancient Greek word zeto (ζήτω), which means “to live,” and which became the name of the piece. Around the curved base, Shelley sculpted Greek words for technology/science/ skill/physician/healer, and human/soul/spirit.

“Some people see a flower or a swan and I’m okay with that,” she says. “For me, To Live was a way to give back, not just to express my experience, but to do something for my doctors. Sometimes art comes from gratitude.”

Before moving with her husband back to Colorado, where she is from, she gave a copy of the piece to her doctors in Minnesota. Then, when her cancer started growing again in February 2018, Shelley’s Minnesota oncologist

suggested she look up a former trainee of his who happened to be working at University of Colorado Cancer Center. Only, by this time, the “trainee,” Thomas Flaig, MD, had become an internationally recognized expert in the treatment of bladder cancer (and is now Vice Chancellor for Research on the Anschutz Medical Campus).

“I’m a warrior, I’m pissed off, so I decide to name my tumor,” Shelley says. “The tumor’s name is Bill. I’m Uma Thurman and I’m going to kill it. I meet Dr. Flaig and say, ‘I’d like to introduce you to Bill – we’re going to Kill Bill.’”

Shelley and Flaig hit it off immediately.

“I have to have a specialist who is running clinical trials because I’m right at that edge – I feel like I’m bodysurfing a wave of new treatments. I can’t have some generalist who says I just want to check out the journals,” Shelley says.

In a new state, with a new doctor, and with a new iteration of her cancer, Shelley felt herself drawn to new symbols in her art.

NEBRA SKY SWORDS Along with other treatments, Shelley and Flaig chose radiation to fight a tumor in her neck and surgery to remove 19 compromised lymph nodes.

“I’m under the machine getting radiation and they say it’s a linear accelerator and I say, ‘Well that sounds like a weapon!” Shelley says. At the time, she was working on a piece inspired by the discovery of a Bronze Age artifact found in Germany, called the Nebra Sky Disk. “Along with the disk, they found daggers and chisels and swords, and I said, ‘Oh, I want to do that!”

The idea became the piece she calls Nebra Sky Swords.

“I have had my moments of anger, shaking my fist at the sky, but the Sky Swords is a different kind of anger, an old, mature anger that is going to pick the right weapon. I’m not slashing away with the sword, I’m using photons – the rising

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warrior is finding the right weapon to fight a battle,” she says.

At her last radiation treatment, Shelley looked up at the accelerator to find that her technicians had taped a picture of Uma Thurman to the machine.

“I burst into tears,” she says, chuckling at herself, “a warrior who falls apart in a good way.”

To fight the remaining cancer in her lymph nodes, Flaig and Shelley decided on an innovative treatment that had just earned FDA approval in December 2019.

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BREAKTHROUGH The drug enfortumab vedotin is actually two drugs hooked together – a targeting molecule (enfortumab) that seeks out cancer cells and a chemotherapy molecule (vedotin) that is only activated once it’s been pulled inside a cancer cell. Sending chemotherapy to cancer cells, and only to cancer cells, lets patients use higher doses with fewer side effects.

“Dr. Flaig told me about this last spring and I was like, ‘Oh really, a Trojan horse!”

Shelley says. “As the horse prances, it’s

breaking through the platform, thus the name Breakthrough.”

Shelley started the drug in January 2020, just weeks after it was approved, and in March 2020 she got the results of scans that would show whether or not the drug was working.

“I’ve had so many scans, I don’t get very anxious anymore. But this one for sure was more important.”

Like a medicine that tastes bad, she “had a feeling this was working, because I was having low-level side effects – nausea, fatigue, hair loss, at a super low

level – I completely function through it, but since I’m having side effects, I think it’s working,” Shelley says.

She was right. The scan showed a significant reduction in the size of every cancerous lymph node. Some shrank back to their precancerous size and all shrunk back from their peaks.

“It’s been a miracle walk and as I told Dr. Flaig, considering the bad luck of getting cancer, I’ve been completely lucky the whole time, riding the wave of these new therapies, staring in 2015 on the first immunotherapy and now this new drug that just got approved,” Shelley says.

The news has Shelley thinking about life beyond cancer.

NEBRA’S SEVEN SISTERS “I think all the time about the language I use to describe what I’m going through,” Shelley says. “Sometimes I use battle metaphors: We fight a battle, we win or lose the battle, we have weapons. A battle metaphor means there are conflicting sides, something you’re fighting against, and there is a resolution or result, a winner and a loser,” Shelley says. “Then sometimes it’s more like a journey. When you talk about a journey, it’s also a story, but it’s not so intense or identifiable who is on what side, or the outcome.”

“The biggest piece of getting good news was my husband and I looking at each other and saying, ‘Wait, we have a chance of growing old together!’ I never think about being cured. I don’t use that word. But if I can live the life I live with my cancer as a chronic condition that’s not life threatening, I’ll take it. I think I have a little arthritis in my thumb and a problem with a knee and I’m so excited because it’s like all of a sudden I’m having a normal aging process!”

Shelley is also playing more music, providing accordion and other keys for a bluegrass-inspired trio she plays in with her husband and a friend.

“Here’s the deal: I have a good attitude. I have to have a kidney removed? Fine, I have two! I have traveled, I play music with my husband, I dance,” Shelley says. “And I think cancer has made me better in all ways. It has made me a better artist. And it has taught me to take myself seriously as an artist and to know I have something to give the world. I know I’m riding on something larger than myself.”

When she dreamt about the Seven Sisters of the Pleiades, “it was the pure heart of me as an artist going ‘that’s it,’” she says. “This last piece is more gentle. It has more female energy around it. It’s more connected to the idea of journey than battle.”

Nebra’s Seven Sisters, which she is still working on, will be the centerpiece of Shelley’s work at Loveland’s Art in the Park virtual auction in August. It shows seven female figures based on the sisters emerging from a horizontal disc. And the fading figure of Merope, one of the seven Pleiades, doesn’t necessarily represent death: “So many of the pieces I’ve done are about my story, my cancer. Merope might be about cancer, but I think it shows I’m ready to tell some other people’s stories. I feel an interest, a curiosity about telling other people’s stories. I’m not too anxious about things: I know I’m just on the track. I know I’m where I need to be.”

Shelley says.

As Merope fades into a comet, Shelley sees herself fading from the center of her cancer journey.

SHELLEY KERR

C3: SUMMER 2020

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Reversing

a Miracle RISE IN VAPING THREATENS TO REVERSE DECADES OF SMOKING DECLINE

By Taylor Abarca In the midst of a global pandemic, it seems odd to be asking my 18-year-old neighbor about the dangers of vaping. However, keeping a safe six-foot distance away and wearing homemade masks, we’re able to hold a decent conversation across the front lawn. My question is simple: Is vaping dangerous? His answer: “I don’t know, but I think it is safer than smoking a cigarette.”

Safer than smoking a cigarette. Is that like saying Safer than taking a selfie with a bull elk?

In what has been called a public health “miracle,” many health care professionals believe the United States was just

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one generation away from wiping out smoking tobacco almost completely. Decades of stopsmoking initiatives have decreased the smoking rate in adults from 42% in 1965 to 13.9% in 2017, and the number continues to fall. Now, it seems that the rise in popularity of vaping products, and the misinformation around them, may be on track to reverse that miracle.

(NOT) A SMOKING CESSATION TOOL

The first commercial e-cigarette was invented in 2003 by a Chinese pharmacist. The kicker? He claims that he invented the device after watching his father die of lung cancer and didn’t want to face the same fate. By 2007, the e-cigarette was patented in the United States. The summary of the product by the United States Patent and Trademark Office describes it as “an electronic atomization cigarette that functions as substitutes for quitting smoking and cigarette substitutes [sic].”

“But there is currently not enough data that shows e-cigarettes help people quit smoking to make this claim,” says Meghan Buran, MPH, senior professional research assistant in the Colorado School of Public Health. “They are not prescribed by medical professionals because they are not regulated by the FDA and have unknown risks.”

However, a quick Google search finds many anecdotal stories of people being able to quit thanks to e-cigarettes.

“People who have truly been able to quit smoking cigarettes because of e-cigarettes are not the norm by any means. Even if there are people who have been able to quit, there are not enough systematic reviews and meta-analyses to prove e-cigarettes helped, or that this strategy works on a population level,” says Buran.

“Although they may have quit smoking cigarettes, if they are continuing to use e-cigarettes in their place, they are still getting nicotine. Many times, these nicotine levels are higher than a traditional cigarette, making them more addictive.”

The bottom line? The medical community does not consider e-cigarettes as a smoking cessation tool. That doesn’t mean it’s impossible for some form of e-cigarettes to be used with some smokers, just that in their current form and with their current use, e-cigarettes aren’t the cessation tool put forward by the vaping industry.

“There is a world in which vaping products may be used as a way to stop smoking under the care of a physician,” explains Buran. “In this world, the products would be approved by the FDA, regulated, and the nicotine levels in the e-cigarette would be decreased over time until it reached zero.”

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THE “VAPING” GENERATION

Vaping is on the rise in U.S. youth, and it is not by a small amount. 11% of high schoolers reported using e-cigarette devices in 2016. Just three years later that number increased to 28%. Researchers from the FDA and CDC estimate that approximately one million teens use e-cigarettes daily, which is equivalent to one in every 17 high school students. The product of choice for more than half of the users is a sleek, small, USB-looking device called Juul.

“Juuls are especially scary because the liquid that is used in them can contain nicotine at incredibly high levels,” explains Buran. “If someone goes through two pods a day, that is the equivalent of smoking two packs of cigarettes in terms of nicotine levels.”

Because Juuls, like all other e-cigarette devices, are not regulated, they do not need to list their ingredients.

“Studies have shown that teens honestly do not think there is nicotine in Juuls,” says Buran. “They think that what they are doing is essentially harmless when in fact they are taking in enormous amounts of nicotine.”

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Nicotine, a highly addictive chemical found in nearly all cigarettes and e-cigarettes, has been linked to heart disease and increased risk of strokes in the general population. In teens and young adults, however, nicotine is especially dangerous.

“Young people that use nicotine have a higher risk of developing psychiatric disorders and cognitive impairments because of the effect it has on their still-developing brains,” explains Buran. “Nicotine is incredibly addictive. It is also incredibly hard to quit. The sad part is most teens don’t realize that the products they are using, such as Juul, have high amounts of nicotine in them. They are becoming addicted without knowing it.”

NEXT SMOKING EPIDEMIC? As the number of young adults and teens using e-cigarettes increases dramatically each year, public health experts are concerned we could be on the cusp of the next smoking epidemic in the United States.

“We were so close to being done with the tobacco epidemic,” says Buran. “Now we have a whole generation of people using these products and we don’t know what the long-term effects will be.”

One effect of vaping that is becoming more clear? Studies show that e-cigarette users are more likely to go on to use tobacco-based products like cigarettes. Some findings suggest that users are three times more likely to pick up a cigarette than non-users.

“We might not know the long-term effects of vaping itself, but we do know the long term effects of cigarettes,” says Buran. “E-cigarettes

may be reversing the public health trend that has been taking place for decades.”

In addition to being a “gateway” habit of sorts, vaping products seem to be making smoking socially acceptable.

“It is common to see people vaping these days, in parks, at concerts, and even in school hallways,” says Buran. “Just a few years ago the idea of smoking anything was generally frowned upon. Now, vaping products are making it socially acceptable for young people.”

FEAR OF THE UNKNOWN The unknown effects of vaping and e-cigarettes keep many public health professionals up at night.

“The bottom line is that vaping is not harmless,” says Buran. “We know that vaping products have been linked to serious lung disease and even death in some cases.

We don’t know if it leads to cancer or other serious, long term health problems, like smoking does. We don’t know if it leads to other problems that we are not aware of yet.

There are too many unknowns at this point.”

That’s the thing about long-term effects: It will likely take decades before we know the extent of vaping’s health effects.

“By that time, we may be dealing with multiple generations of people using e-cigarettes and have a new public health crisis on our hands,” says Buran. “My fear is that I will be looking back to today and saying we should have done more to stop this when we could.”

C3: SUMMER 2020

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RICH AND PEGGY MCCLINTOCK WITH SAKETH GUNTUPALLI, MD, HEAD OF THE UNIVERSITY OF COLORADO SCHOOL OF MEDICINE DIVISION OF GYNECOLOGIC ONCOLOGY

After Daughter’s Passing, Rich and Peggy McClintock Help CU Build Toward Early Detection of Ovarian Cancer

In July 2019, Emily McClintock was on vacation in Maine with her husband, Jason, when she felt sick and was airlifted to Portland with internal bleeding.

A tumor on her ovary had burst. It was Monday. On Saturday, she passed away.

Emily was 44 years old.

“It was that sudden and that quick,” says her father, Rich McClintock.

When Jason called with the diagnosis, Rich and his wife, Peggy, had flown overnight to Boston and drove to Emily’s bedside in Portland. After open heart surgery to stop the flow of blood clots, Emily couldn’t be moved for two weeks.

“For three or four days, she got a little better, a little worse,” Rich says.

Rich and Peggy spent this time coordinating a plan to transfer Emily’s care to University of Colorado Cancer Center, and then got on a quick flight home to grab clothes.

“We got on the plane and she passed away,” says Rich.

Breast cancer is often discovered early with a mammogram; there are blood tests for prostate cancer; pap smears detect cervical cancer; colonoscopies can find and even correct early-stage colorectal cancer; and doctors are even finding lung cancer at treatable stages with screening for high-risk populations. But there is no early-detection test for ovarian cancer. By the time a patient is diagnosed, ovarian cancer is often advanced, leading to survival rates that are well below those for

EMILY MCCLINTOCK

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other cancers.

S U P P O R T E R

F CUS

MCCLINTOCK FAMILY WITH KIAN BEHBAKHT, MD (CENTER RIGHT) “When I was very young, polio was a killer and

dinners at his house one night. He’s working long

online, symptom-based screening questionnaire,

they put a full court press on that and came up

hours on coronavirus now, doing good work. It’s

followed by a blood test for those found to be

with a vaccine. Then on TV, President Kennedy

the least we can do!”

at risk, “we could identify about 10,000 of these

committed to the country ‘We are going to the moon.’ We had no idea how to do it, but we went to the moon. GM says it’s going to switch from making cars to making ventilators and seven days later it happens. Now we need that kind of effort for ovarian cancer. We need a marker that helps us find ovarian cancer early, when we can still do something about it,” Rich says.

Working with Guntupalli and the CU Anschutz

people at a treatable stage,” he says.

Medical Campus Office of Advancement, the

Turning Behbakht’s plan into reality will require

McClintocks helped to establish an endowed

more robust research and resources.

chair for former division head, and current CU Cancer Center member, Kian Behbakht, MD. In the 1990s, Behbakht was part of the team that discovered the role of the BRCA gene in

“We’re not going to dwell on what happened to Emily. Dwelling won’t bring her back. Instead, we’re going to fix it,” Rich says.

ovarian cancer risk. Now, in addition to symptom-

Discussions with CU Anschutz Medical Campus

The family is working with the CU Anschutz

screening and preventive treatments (“We would

are underway for additional ovarian

Medical Campus to make that happen. They

have 70% less ovarian cancer by removing

cancer strategies including recruiting top

started by meeting with Saketh Guntupalli, MD,

fallopian tubes after child-bearing age,” Behbakht

researchers to work alongside Guntupalli and

head of the CU School of Medicine Division of

says), Behbakht has set his sights on pinpointing

Behbakht, and establishing CU Anschutz Medical

Gynecologic Oncology and CU Cancer

the unique genetics of ovarian cancer that could

Campus as a national hub of ovarian cancer

Center member.

lead to an early-detection test.

research and treatment.

“The passion and energy of these doctors at CU

“We need a Cologuard-like screening that you can

“We want the reward for Emily’s loss, if there

Anschutz is just incredible,” Peggy says. “After our

give to a whole population of women,” Behbakht

is such a thing, to be a positive outcome for many,

meetings, we’ve become good friends with

says. There are about 13,000 ovarian cancers

many women,” Rich says.

Dr. Guntupalli – we even dropped off a couple

diagnosed in the United States every year. With an

Get more CU Cancer Center news on our blog: www.coloradocancerblogs.org

C3: SUMMER 2020

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UNIVERSITY OF COLORADO

SUMMER 2020 www.coloradocancercenter.org

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C3: Collaborating to Conquer Cancer Published twice a year by University of Colorado Anschutz Medical Campus for friends, members, and the community of the University of Colorado Cancer Center.

(No research money has been used for this publication.)

Contact the communications team: Jessica Cordova | 303.724.1074 | Jessica.2.Cordova@cuanschutz.edu Design: Candice Peters | Design & Printing Services University of Colorado The CU Cancer Center Consortium Members UNIVERSITIES

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Cancer Doesn’t Stop for a Pandemic T H E

M E S S A G E

Prevent and Conquer Cancer. Together.

CU Cancer Center to look inside cells, DNA, and

At University of Colorado Cancer Center, that’s

the components of the immune system for new

our vision. During COVID-19, that vision hasn’t

understanding of how COVID-19 infects and kills,

changed and, in fact, may be more important

and how we can stop it.

now than ever before.

FROM THE DIRECTOR RICHARD SCHULICK, MD, MBA DIRECTOR, UNIVERSITY OF COLORADO CANCER CENTER CHAIR OF SURGERY, UNIVERSITY OF COLORADO SCHOOL OF MEDICINE

Join Richard Schulick, MD, MBA, and his colleagues for a panel conversation on the state of the University of Colorado Cancer Center on Thursday, July 23 at 9:30 a.m.

For more information please contact RSVP@cuanschutz.edu or call 303-724-7823.

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Our response to this pandemic not only

Because of COVID-19, our patients have suffered,

demonstrates our ability to come together

our research is delayed, our faculty and staff are

as a community to fight cancer while fighting

reorganizing their work and their lives, and we have

coronavirus, but it shows how absolutely essential

needed to think creatively to avoid pausing our

these activities are. Through this pandemic, we see

educational efforts altogether. I have seen many

the power of health care and medical research. In

terrible things come from this pandemic. But I have

some cases, like our inability to provide adequate

also seen it tie people together.

testing, we also see our shortcomings.

It’s one thing to help people whose lives are in

In this challenge, there is also opportunity. As the

danger. It’s a totally different set of circumstances

pandemic evolves, our goal will be to not only

when your own life is in danger. Yet as I walk

reestablish our original trajectory of research and

through UCHealth University of Colorado Hospital,

care, but to use this time of crisis and awareness

I see nurses, doctors, trainees, technicians and staff

to evolve, ourselves. To do so, we will need your

working selflessly to take care of critically ill patients,

help. Your involvement, your advocacy and your

from new cases of COVID-19, to our cancer

support make us able to meet the current crisis,

patients who continue to need not only treatments,

recover once we are passed its peak, and grow into

but also access to our multidisciplinary clinics and

a future with a new appreciation for science that

life-saving clinical trials. And while most of our labs

leads to cures.

have been closed, others have refocused their efforts to discover COVID-19 treatments, tests and vaccines. Meanwhile, researchers on the front lines of virology and immunology from around the state are using the technology resources of

I am so proud. I am so honored. And I am so optimistic for the future of cancer research at our center and beyond.