By Lisa Y. Garibay
It moves quickly, faster than you'd believe or fear, an invader slinking through tiny spaces, using its host's own system to further its multiplication, proliferation, path of destruction.
It is a terrifying threat that has ended many lives and irrevocably altered many more.
And it takes an army to face it.
In contrast to the dark, closed environment of the body in which cancer creeps, the students and faculty within the Kirken Molecular Mechanism Cancer Laboratory move in light. Sunshine from windows streams onto countertops, where run-of-the-mill test tubes sit in holders adjacent to machines usable only by those highly trained – which in this case includes students from The University of Texas at El Paso where the laboratory is housed. The students are at all levels of collegiate education, but what unifies the eager freshman with the seasoned postdoc is a passionate belief that their work can tip the domino it takes to topple the system by which cancer grows, and by doing so, save lives.
The leader of this army is Robert Kirken, Ph.D., dean of UTEP’s College of Science and principal investigator for the University’s Border Biomedical Research Center (BBRC), which studies health issues that most affect the Paso del Norte region and its majority Hispanic population. Kirken’s lab is primarily focused on understanding the complex communication inside cells so that new therapeutic strategies can be developed to treat diseases such as cancer, rejection of transplanted organs and autoimmune disorders.
Kirken’s lab is also cultivating greater diversity within the scientific community, providing early access to research work for the mostly Hispanic student body at UTEP. Research Assistant Professor Georgialina Rodriguez, Ph.D., keeps things running by overseeing the day-to-day needs of every project.
“We’re a big lab, 16 strong, and that’s three postdocs, some graduate students, and quite a number of undergraduate students,” she said. “These guys are sharp. Before one semester is even over, they’re working independently on their own. We’re very much like a family. In a way, we’re all doing this work for somebody.” Roberto “Bobby” Garcia is a senior majoringin biology with a concentration in biomedical science. He is in the process of interviewing with medical schools for the fall 2017 semester and hopes to one day work in pediatric oncology.
He began volunteering in the lab during his freshman year – one year after he was diagnosed with cancer as a high school senior.
“That’s what got me interested in the research and medical aspects of science,” Garcia said. “So, for me, it was 100 percent personal.”
Junior Edmundo Esparza – a biology major with a biomedical concentration and a participant in the University’s A-PRIME TIME accelerated medical school preparation program – appreciates how the lab has helped him hone practical skills like time management and prepared him for medical school in the fall, hopefully in Houston, to gain more expertise
in oncology and eventually return to El Paso to practice medicine.
Blanca Ruiz received her bachelor’s and doctoral degrees from UTEP and is now a postdoctoral fellow in the Kirken lab, where she has been continually inspired to persist in her microbiology investigations.
“You listen to all the research that the professors are doing here and how it’s expanding into working with hospitals, and how you can actually get your hands on some patient samples and really contribute to the health of individuals,” she said.
Elisa Robles is a third-year Ph.D. student in pathobiology who is motivated by the fact that the lab works with samples from patients in the area.
“I think that is very good because a lot of the research that has been done is on other kinds of populations,” Robles said. “That’s the thing that I like – to try and do research that is going to have an immediate impact on my community.”
And then there’s Derrick Oaxaca. Like Garcia and Esparza, he asked to work in the Kirken
lab early on in his undergraduate studies,
and came to the lab “as green as green could be,” Kirken recalled with both affection and admiration.
Oaxaca was placed under the lab manager at the time, Jeremy Ross, Ph.D., who has since left UTEP to work as an oncology scientist with pharmaceutical company AbbVie. Together, they investigated rare and aggressive cancers seen in El Paso. After several years in the lab, Oaxaca received his bachelor’s degree from UTEP and Kirken recruited him into the graduate program to pursue a Master of Science degree under his mentorship.
“I was placed on my own project dealing with investigating how cell signaling within cancer can be manipulated to overcome disease,” explained Oaxaca, who is now a second-year medical student at Texas Tech University Health Sciences Center El Paso Paul L. Foster School of Medicine. “My research was specifically focused on chronic myeloid leukemia containing the T315I mutation, which is a mutation known to be resistant to almost all therapies.” He also involved himself in other lab projects, including sequencing the genome of tumor samples from El Paso-area patients in order to identify genes that may be driving cancer, and exploring personalized medicine by developing ways to identify more precise therapies for aggressive cancers.
These experiences were possible in part because of partnerships Kirken developed with local physicians. One of these alliances was with pediatric oncologist Benjamin Carcamo, M.D., and pediatric pathologist Harry Wilson, M.D. Both knew that even though the survival of pediatric patients had improved over the years, a group of patients remained that would fail all therapy. The doctors also believe that the presentation and behavior of pediatric cancer in Hispanics was unique and unrepresented in the medical literature, and that the strong Hispanic presence in El Paso made it ideal to study pediatric cancer in this growing but poorly understood population. For these reasons, they were very willing to contribute to the greater understanding
of pediatric cancer by collaborating with Kirken. The collaboration started several years ago with the submission of tumor samples to Kirken’s lab and continued when Carcamo and Wilson joined the El Paso Children’s Hospital pediatric oncology team in 2012. The understanding of the biology of pediatric cancer they had gained through this collaboration made them believe they were ready for the next step.
It all came together when Lisa Hartman, M.D., a pediatric oncologist at El Paso Children’s Hospital who works with Carcamo and Wilson, sent a brain tumor sample from a 2-year-old female patient to Kirken’s lab. Hartman had first met Kirken when she came to El Paso to interview for her position, at which point they discovered mutual research interests.
“We talked about how we could collaborate with getting clinical samples to his lab and really work together to further the personalized medicine approach of using targeted therapy that we both share an interest in,” she recalled.
The toddler with a brain tumor provided a perfect opportunity to do so.
Most cancer occurs in adults, which means that the most research and treatment options are geared toward those over 18 whose bodies are almost completely opposite those of
children. They’ve reached a stopping point when it comes to the kind of development it takes to grow into a whole, healthy human, and are strong enough to tolerate a battery of drugs and radiation that can often destroy cancer but also decimate healthy cells in the process.
The most common cancers among children are leukemia, lymphoma and brain tumors. The first two zip through bodywide networks that serve as highways for the cancers to wreak havoc in many places at once. The third takes root in the most important organ we possess, the one that gives us language and memory and emotion and self-awareness and everything else that makes us human alongside the vital processes we need to survive – breathing, a beating heart, the ability to eat, the circulation of our blood.
In children, brain tumors present a difficult conundrum for the physicians who encounter them due to how much change the organ is undergoing; change that affects a child’s future. Attack the tumor too aggressively and critical function can be destroyed. Approach it too timidly and the tumor may spread to become uncontainable.
When the pediatric oncology team at Children’s Hospital encountered a 2-year-old child with a brain tumor that wasn’t responding to treatments in their arsenal, an approach that resulted from countless hours of students and educators running experiments in the Kirken lab is what worked.
The child had been diagnosed with a supratentorial primitive neuroectodermal tumor, or SPNET, which means it was found in the cerebrum, the largest part of the brain. It controls voluntary muscle function along with speech, emotion, thought, reading, writing and the capacity to learn – so much critical to a child’s development and later well-being.
SPNETs are rare, accounting for approximately 2 percent of all cancers that affect the brain or central nervous system in children. The tumors are notoriously aggressive. The survival rate ranges from 30 percent to 60 percent.
“You’ll read in the textbooks, ‘This is rare condition; you’ll never see it.’ However, in El Paso, you’ll see it,” Oaxaca said. “That’s the perk of going to medical school on the border – you see patients from a third world country come in, patients come in from Mexico who have diseases that are listed as rare in any medical textbook.”
When a cancer is so rare, research on it is just as elusive. There’s hardly a plan A for treatment, much less a plan B or C. Much of the work done in the Kirken lab is on understanding cancer on a molecular level so that any weakness in those molecules can be exploited and a treatment already in existence can be matched up to attack them.
And that’s where Oaxaca – the guy who first thought he wanted to be an engineer, the student who had scarcely left childhood himself – came in.
“Derrick was studying. He was learning the pathways, he was understanding the assays, he was trying to troubleshoot why things weren’t working,” Kirken said. “He was critical because he took on the challenge to better understand these medically complex tumors.”
Oaxaca explained, “We were able to see inside of the tumor at a molecular level the switches that were turned on. And these switches that were turned on coincided with the drug that treated leukemia, so we were like, ‘You know what? In theory, it should work."
What wasn’t working were standard treatments for the tumor.
“We didn’t want to give her radiation, which is considered a possible option for this type of brain tumor, but we try not to do that to avoid the side effects on the developing brain,” Hartman said. “So we were talking about what would be the best treatment for her that would cause the least amount of side effects so that she could grow and have a normal childhood.”
Conventional chemotherapy – where drugs are given to kill the cancer, but may also kill off healthy cells and cause dire side effects in the process – is typically used on rare cancers.
But that method had failed the 2-year-old and the tumor was growing, compromising her life. Furthermore, her tumor was so large that performing surgery would have had potentially fatal results.
When the little girl’s parents were presented with the choice of an experimental approach and informed of its risks as well as benefits, they agreed to try it. Within a month of receiving the drug, the child’s tumor had shrunk significantly. Within several more months, it had retreated to the point where
a surgeon was able to go into the brain with minimal invasion and remove what was left of the tumor completely.
These therapies are referred to as targeted because they bind within the cancer molecule and keep its reproductive switch from flipping on while leaving every other healthy cell in the body alone. Side effects plummet. Damage is minimized. This is what the Kirken lab, and every physician treating cancer patients, is going for.
But none of this innovation would have made it out of the lab were it not for the willingness of local physicians to join forces with the researchers.
“What do you do then when there’s really no schematic to treat the disease?” Oaxaca asked. “You need people like Dr. Hartman and Dr. Carcamo, who collaborate with experts in the area and utilize local resources to combat these really aggressive cancers.”
“That it was actually feasible to get a tumor sample, test it in the lab, bring that information then back to the patient, offer a drug that we could actually have access to
– the stars all aligned the proper way in this case,” Hartman said. “It has to be just a lot of collaboration that happens, a lot of working and not giving up.”
This child’s story isn’t the end. Another patient, this time an adolescent whose tumor was growing fast and not responding to standard methods, also experienced a successful outcome from a treatment developed by the Kirken lab.
As a medical student, Oaxaca eagerly works on an astonishing range of projects to better healthcare locally. As a board member of the Cielo Vista Optimist Club, he proposed that the organization give proceeds from its annual fundraising events to the Kirken lab to be used for lab and testing supplies as well as fees required for students to attend conferences or travel to present papers on their work. The organization’s board agreed that those efforts make the student learning experience stronger and continue progress toward successful clinical trials that can turn into advanced lifesaving treatment right here in El Paso.
The UTEP alumnus also is a delegate for his medical school to the Texas Medical Association and serves as its representative at caucuses throughout the year. He recently visited Washington, D.C., to meet with members of Congress to discuss issues involving medicine and politics. When he’s not juggling all of this and more, he is still working with Hartman on new research related to beating childhood cancer.
“We want to have a regular, systematic way to get patient samples, get them to the labs where they need to be tested, get all of the regulatory requirements all in a row, so that’s what we’re looking at in the future,” Hartman said. “Up till now, we’ve kind of done it just on a case-by-case basis.”
However, the knowledge gained with Kirken’s collaboration and the experience with this and other selected cases is helping the pediatric oncology team at El Paso Children’s Hospital put together a research protocol to treat patients who had failed all standard therapy and to better understand pediatric cancer in Hispanics. This protocol will include the collaboration of pediatric oncologists, pediatric pathologists, pediatric geneticists at El Paso Children’s Hospital
and Texas Tech University Health Sciences Center El Paso, chemotherapy researchers and the Kirken Molecular Mechanism Cancer Laboratory at UTEP.
In addition to the scientific breakthroughs, the whole team is aiming for a total cultural shift that will change local perceptions about cancer and its treatment.
“At the end of the day, it’s about educating everybody; it’s about educating even people who have been in the business for a very long time,” Kirken said. “You’re never too old to learn, and I think we really owe it to the people here in this region to try to do the best that we can to provide cutting- edge care. And part of that is what we’re doing right now. We’re training this next generation of scientist-clinicians. If we can keep 20 Derricks, think about how much better El Paso would be.”