Cory Dobson, Author at Sanford Burnham Prebys - Page 8 of 42

Author: Cory Dobson

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Scientists design potential drug for triple-negative breast cancer

AuthorMonica May
Date

February 16, 2021

Noise and artifacts image: MAMMOGRAM Medical image showing CA right breast 3 cm fluid collection at MUQ ,near nipple right breast is noted and this may be seroma

Drug candidate blocks autophagy, a cellular recycling process that cancer cells hijack as a way to resist treatment

Scientists at Sanford Burnham Prebys Medical Discovery Institute have designed a next-generation drug, called SBP-7455, which holds promise as a treatment for triple-negative breast cancer—an aggressive cancer with limited treatment options. The drug blocks a cellular recycling process called autophagy, which cancer cells hijack as a way to resist treatment. The proof-of-concept study was published in the Journal of Medicinal Chemistry.

“Scientists are now learning that autophagy is one of the main ways that cancer cells are able to survive, even in the presence of growth-blocking treatments,” says Huiyu Ren, a graduate student in the laboratory of Nicholas Cosford, PhD, at Sanford Burnham Prebys, and first author of the study. “If all goes well, we hope this compound will stop cancer cells from turning on autophagy and allow people with triple-negative breast cancer to benefit from their treatment for as long as possible.”

Cells normally use autophagy as a way to recycle waste products. However, when cancer cells’ survival is threatened by a growth-blocking treatment, this process is often “revved up” so the cancer cell can continue to receive nutrients and keep growing. Certain cancers are more likely to rely on the autophagy process for survival, including breast, pancreatic, prostate and lung cancers.

“While this study focused on triple-negative breast cancer, an area of great unmet need, we are actively testing this drug’s potential against more cancer types,” says Cosford, professor and deputy director in the National Cancer Institute (NCI)-designated Cancer Center at Sanford Burnham Prebys and senior author of the study. “An autophagy-inhibiting drug that stops treatment resistance from taking hold would be a great addition to an oncologist’s toolbox.”

About 15% to 20% of all breast cancers are triple negative, which means they do not respond to hormonal therapy or targeted treatments. The cancer is currently treated with surgery, chemotherapy and radiation, and is deadlier than other breast cancer types. If the tumor returns, other treatments such as PARP inhibitors or immunotherapy are considered. People under the age of 50 are more likely to have triple-negative breast cancer, as well as women who are Black, Hispanic, and/or have an inherited BRCA mutation.

An optimized drug

In this study, the scientists optimized a first-generation drug they created in 2015. The result is a compound called SBP-7455 that blocks two autophagy proteins, ULK1 and ULK2. SBP-7455 exhibits promising bioavailability in mice and reduces autophagy levels in triple-negative breast cancer cells, resulting in cell death. Importantly, combining the drug with PARP inhibitors, which are currently used to treat people with recurrent triple-negative breast cancer, makes the drug even more effective.

“We are hopeful that we have found a new potential therapy for people living with triple-negative breast cancer,” says Reuben Shaw, PhD, a study author and professor in the Molecular and Cell Biology Laboratory and director of the NCI-designated Cancer Center at the Salk Institute. “We envision this drug being used in combination with targeted therapies, such as PARP inhibitors, to prevent cancer cells from becoming treatment resistant.”

Next, the scientists plan to test the drug in mouse models of triple-negative breast cancer to confirm that the compound can stop tumor growth in an animal model. In parallel, they will continue optimization efforts to ensure the drug has the greatest chance of clinical success.

“Triple-negative breast cancer is one of the hardest cancers to treat today,” says Ren. “I hope that our research marks the start of a path to successful treatment that helps more people survive this aggressive cancer.”

Additional study authors include Nicole A. Bakas, Mitchell Vamos, Allison S. Limpert, Carina D. Wimer, Lester J. Lambert, Lutz Tautz, Maria Celeridad and Douglas J. Sheffler of Sanford Burnham Prebys; Apirat Chaikuad and Stefan Knapp of the Buchmann Institute for Molecular Life Sciences and Goethe-University Frankfurt; and Sonja N. Brun of the Salk Institute.

This work was supported by the National Institutes of Health (P30CA030199, T32CA211036), Epstein Family Foundation, Larry L. Hillblom Foundation (2019-A-005-NET), Pancreatic Cancer Action Network (19-65-COSF), SGC—a registered charity that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada through Ontario Genomics Institute [OGI-196], EU/EFPIA/OICR/McGill/KTH/Diamond, Innovative Medicines Initiative 2 Joint Undertaking (875510), Janssen, Merck KGaA, Merck & Co, Pfizer, São Paulo Research Foundation-FAPESP, Takeda, and Wellcome.

The study’s DOI is 0.1021/acs.jmedchem.0c00873.

Institute News

Meet immunologist Jennifer Hope

AuthorMonica May
Date

February 12, 2021

Jennifer Hope photo in lab

Hope’s research aims to help cancer immunotherapy work for more people

It’s not an overstatement to say that immunotherapy—an approach that uses our own immune system to kill a tumor—has revolutionized the treatment of cancer. Doctors continue to report incredible results, including tough-to-treat tumors seemingly melting away. However, the treatment doesn’t work for everyone, and even if it does work initially, it often stops working as time goes on.  

Jennifer Hope, PhD, a postdoctoral researcher in the Bradley lab at Sanford Burnham Prebys, is working to find ways to make cancer immunotherapy work for more people. We caught up with her as she prepared to take the virtual stage at the Diversity and Science Lecture Series at UC San Diego (DASL) to learn more about what she wishes people knew about science and whom she admires.

Did you always know you wanted to be a scientist?
I always had an interest in science, but at first I wanted to go a totally different route. I was an athlete in high school and college—I played tennis—and really wanted to go into sports medicine. Then I had my first real experience being in a lab in college, and I was hooked. I liked how hands-on it was and how I could keep asking questions. As my family knows, I’ve always been one to ask a lot of questions and always ask why. I found that being in the lab that was my opportunity to keep coming up with new questions, and finding answers that will impact people’s lives.

What do you research, and what is your greatest hope for your work?
I’m trying to understand why the immune system—specifically, T cells—seems to turn a “blind eye” to tumors, which it doesn’t do to other foreign invaders like viruses. My ultimate hope is that we use this information to create better cancer immunotherapies, particularly for skin cancer, which is still really deadly.

What do you wish people knew about science?
That it can be a lot of fun! Most people have this perception of science as being very boring. You see X and you do Y. That part can be true. But there’s a lot of opportunity for creativity and to come up with different ways to ask the same question. Some of the best scientists are incredibly creative people.

How would your coworkers describe you?
Motivated and always willing to try new things.

When you aren’t working, where can you be found?
Reading a book. My family started a book club to stay connected during the pandemic. We just read The Food Explorer by Daniel Evan Stone, which was fascinating. It’s about a botanist who is responsible for transforming what food looked like in the U.S. at the turn of the century. I don’t want to give too much away, but it’s because of him that we have cherry blossoms in Washington D.C., and regulations on importing seeds.

Whom do you admire, and why?
My parents. It sounds cliché, but it’s true. They have always been the biggest supporters of my dreams, whether career or personal.

One example that pops into my head is when I was getting my PhD, and my PI moved from Philadelphia to the Netherlands. I had the opportunity to move, too, if I wished. This was obviously a huge step, and I called my parents to talk it through. Immediately, the conversation was about how this would benefit me—the risks and the advantages—and they said they would support me if I wanted to go or not. That meant, and means, the world to me. Ultimately, I did go, and it was an incredible opportunity that I don’t regret at all.

What do you wish people knew about Sanford Burnham Prebys?
That everyone is willing to help each other. You don’t see that everywhere. It is proof that you can do science at an exceptional level without competing with each other.

Institute News

Mining “junk DNA” reveals a new way to kill cancer cells

AuthorMonica May
Date

February 11, 2021

DNA strand and Cancer Cell Oncology Research Concept 3D rendering, abstract background

Scientists unearth a previously unknown vulnerability for cancer and a promising drug candidate that leverages the approach

Scientists at Sanford Burnham Prebys have uncovered a drug candidate, called F5446, that exposes ancient viruses buried in “junk DNA” to selectively kill cancer cells. Published in the journal Cell, the proof-of-concept study reveals a previously unknown Achilles’ heel for cancer that could lead to treatments for deadly breast, brain, colon and lung cancers.

“We found within ‘junk DNA’ a mechanism to stimulate an immune response to cancer cells, while also causing tumor-specific DNA damage and cell death,” says Charles Spruck, PhD, assistant professor in the National Cancer Institute (NCI)-designated Cancer Center and senior author of the study. “This is a very new field of research, with only a handful of papers published, but this has the potential to be a game-changer in terms of how we treat cancer.”

Since the human genome was fully sequenced in 2003, scientists have learned that our DNA is filled with some very strange stuff—including mysterious, noncoding regions dubbed “junk DNA.” These regions are silenced for a reason—they contain the genomes of ancient viruses and other destabilizing elements. An emerging area of cancer research called “viral mimicry” aims to activate these noncoding regions and expose the ancient viruses to make it appear that a cancer cell is infected. The hypothesis is that the immune system will then be triggered to destroy the tumor.

A one-two punch to cancer

In the study, Spruck and his team set out to find the molecular machinery that silences “junk DNA” in cancer cells. Using sophisticated molecular biology techniques, they found that a protein called FBXO44 is key to this process. Blocking this protein caused the noncoding sections of DNA to unwind—but not for long.

“When we revealed noncoding regions, which aren’t meant to be expressed, this caused DNA breakage. This told the cell that something is deeply wrong, and it committed suicide,” explains Spruck. “At the same time, the DNA of the ancient virus was exposed, so the immune system was recruited to the area and caused more cell death. So, we really delivered a one-two punch to cancer.”

The scientists then showed that a drug that targets the FBXO44 pathway, called F5446, shrank tumors in mice with breast cancer. The drug also improved the survival of mice with breast cancer that were resistant to anti-PD-1 treatment, an immunotherapy that is highly effective but often stops working over time. Additional studies in cells grown in a lab dish showed that the drug stops the growth of other tumors, including brain, colon and lung cancers.

The scientists also conducted many experiments to show that this silencing mechanism only occurs in cancer cells, not regular cells. Analysis of patient tumor databases confirmed that FBXO44 is overproduced in many cancers and correlated with worse outcomes—further indicating that a drug that inhibits this protein would be beneficial.

Moving the research toward people

As a next step, the scientists are working with the Conrad Prebys Center for Chemical Genomics to design an FBXO44 pathway-inhibiting drug that is more potent and selective than F5446. This state-of-the-art drug discovery facility is located at Sanford Burnham Prebys.

“Now that we have a compound that works, medicinal chemists can make modifications to the drug so we have a greater chance of success when we test it in people,” says Jia Zack Shen, PhD, staff scientist at Sanford Burnham Prebys and co-first author of the study. “Our greatest hope is that this approach will be a safe and effective pan-cancer drug, which maybe one day could even replace toxic chemotherapy.”

 

Institute News

Hospitals were full. One scientist stepped up.

AuthorMonica May
Date

February 10, 2021

Evan Snyder, MD PhD headshot

Sanford Burnham Prebys physician-scientist Evan Snyder spent two weeks in a gymnasium-turned-ICU, where he cared for people with severe COVID-19

The novel coronavirus has hit California hard, but one area that has been particularly impacted is Imperial County. Last spring, the rural farming region’s two hospitals became overwhelmed with COVID-19 cases—prompting a college basketball stadium to be converted into a makeshift intensive care unit (ICU). Soon, qualified personal were also needed.

Stem cell scientist Evan Snyder, MD, Ph.D., may not be the first person you would think to call on during such an emergency. But as a physician-scientist who works with critically ill newborns, he knows his way around an ICU. He knows how to run ventilators. And perhaps most importantly, he had an urgent desire to help.

“I had already decided I would study this disease from a scientific perspective,” says Snyder, who is working with UC San Diego’s Sandra Leibel, MD, to use “mini lungs” to understand why some people with COVID-19 fare worse than others. “But as I started to see the public health menace it became, I felt like I needed to do more.”

Snyder started to sign up for every volunteer opportunity he could find. However, it wasn’t until the December post-holiday surge in cases when he was deployed to serve in the field. Through the California Medical Assistance Team (CAL-MAT), a group of highly trained medical professionals who provide assistance during disasters, Snyder was deployed to the gym-turned-ICU in Imperial County.

“Although our research examines the impact of the virus on lung cells created from people of many racial and ethnic backgrounds, the degree of disease disparity didn’t hit me at a gut level until this work,” says Snyder. “There’s no question that COVID-19 is unfairly hitting people who are socio-economically challenged and have co-morbidities such as diabetes and hypertension, which are the often the products of a disadvantaged environment.”

“I was like a vampire”

For two weeks Snyder worked through the night, taking down medical histories; giving people oxygen, providing medications such as dexamethasone, remdesivir, anticoagulants and antibiotics; carefully turning people onto their stomachs to ease breathing difficulties or helping individuals walk. He also saw clear patterns emerge.

All of the people he treated had conditions that are linked to poverty. More than 20% of people living in Imperial County live below the poverty line—double the national average. As a result, residents may be more likely to obtain food from food banks and may not have access to regular healthcare—which together can lead to conditions such as diabetes, hypertension or obesity. Many of the people whom Snyder cared for shared that they lived in small quarters with multiple generations, which made quarantining difficult, if not impossible.

“Some people who live in La Jolla and test positive have the luxury of living in a big house. They can afford not to go to work and stay in a separate bedroom while the rest of the family quarantines,” says Snyder. “The people I took care of can’t do that. We need to create places where people who test positive for COVID-19 can quarantine safely away from their families.”

Carrying insights back to the lab

Snyder’s experience has directly informed several new research avenues he plans to pursue.

“We already model real-world COVID-19 infections with ‘mini lungs’ created from different genders and races,” explains Snyder. “But this taught me that we need to better mimic the conditions present in a person who has diabetes or other conditions that create an adverse milieu for their organs and cells.”

This work also imprinted upon him that COVID-19 is more than a lung condition. The risk of blood clots causing strokes, heart attacks or blocking blood flow to the lungs was an ever-present concern.

“It wasn’t just about giving people more oxygen,” says Snyder. “This showed me that we need to focus even more on the vascular and inflammatory components of this disease.”

Lives were saved

Snyder is relieved to report that no lives were lost during those two weeks. He credits the care given—even if relatively primitive—to this success.

“If we weren’t doing what we were doing, about 30% of the people there would have died. And another 30% would have been left with lifelong impairments,” says Snyder. “However, in order to truly tame this virus, we need to find effective drugs, continue to vaccinate as many people as possible and exercise logical public health precautions.”

 

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Meet molecular biologist Jonatan Matalonga-Borrel

AuthorMonica May
Date

February 3, 2021

Jonatan Matalonga-Borrel, PhD in the lab

Matalonga-Borrel is on the hunt for a treatment that could help children born with a rare, life-threatening condition

Thanks to the sequencing of the human genome, scientists have helped parents get answers to the cause of mysterious conditions that have affected their children. Now, researchers are tackling a new challenge: translating this knowledge into life-altering medicines.

Molecular biologist Jonatan Matalonga-Borrel, PhD, a postdoctoral researcher in the Dong lab at Sanford Burnham Prebys, is at the forefront of this effort. We caught up with Matalonga-Borrel as he prepares to take the virtual stage at DASL (the Diversity and Science Lecture Series at UC San Diego) to learn more about his work and his interests outside of the lab.

Did you always know you wanted to be a scientist?
I actually wanted to be an airplane pilot until my senior year of high school. But during the application process, I learned that I have very mild color-blindness, so I had to quickly decide what I wanted to do next. I pivoted to biology, a topic where I had some interest, thinking I would become a teacher. Then, when I was in college, I got the opportunity to complete a lab internship, which is where I discovered my passion for research. I would have never guessed that I would be where I am today, leading a project that might directly help families and children.

What do you study, and what is your greatest hope for your research?
I study Alagille syndrome, a rare disease that affects kids from the day they are born. Many organs are affected, especially the heart and the liver, and almost half of these children die before the age of 19.

Luckily, Alagille syndrome is associated with mutations in only two genes, both belonging to the same pathway, called Notch. This makes our goal easier to achieve: identify drugs that target Notch, which currently don’t exist. I’m excited that we’ve identified a promising option. My greatest hope is to create a medicine that truly helps these children and their families, who currently live without any treatment.

When you aren’t working in the lab, where can you be found?
You will likely find me playing golf at Torrey Pines! There is nothing like playing a twilight round, feeling a slight breeze and looking at the immensity of the Pacific Ocean. With that said, since I became a father, my golfing time has been severely impaired. Now it’s most likely that you’ll find me at home, entertained by the early stages of development of my son…and changing a lot of diapers!

What do you wish people knew about science?
How patient one has to be to move science forward. It can take weeks—or months—of trial and error until a big breakthrough happens.

We live in a world that seems to spin faster and faster. It is critical for our society to understand that proper science is not about rushing experiments. It is about setting the right ones.

How do you think your lab colleagues would describe you?
Upbeat, reliable and organized (hopefully!).

How has the pandemic affected your life?
I had my first baby last June, and the pandemic prevented any relatives to come from our home country, Spain, and meet their first grandchild. Thankfully, we had Skype to get in touch. Looking on the bright side, daycares have never been so clean, and the rate of sickness around kids has dropped significantly!

What is the best career advice you have ever received?

“Have fun and make friends,” from Dr. Eduardo Chini of the Mayo Clinic. It is possible to do great science and have fun—don’t feel guilty about it. My best collaborations came from my greatest friendships among colleagues.

What do you wish people knew about Sanford Burnham Prebys?
It’s an amazing community. Science moves forward thanks to communication and collaboration and it wouldn’t happen without a strong sense of community. This includes wise faculty members who train graduate students and postdocs, an Office of Education and International Services that offers year-round seminars and workshops, and a group I am part of, called SBP-Social Network (SBP-SN), which organizes fun social and scientific events. All of this creates a place where scientific excellence thrives.

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Meet cancer researcher Karina Barbosa Guerra

AuthorMonica May
Date

February 3, 2021

Karina Barbosa Guerra in the lab

Barbosa Guerra is working to find better treatments for a deadly leukemia

For Karina Barbosa Guerra, touring a lab and meeting scientists as part of her Girl Guides troop—Mexico’s equivalent of the Girl Scouts—was a life-changing experience. Suddenly, she could see herself as a scientist.

Today, Barbosa Guerra is a graduate student in the Deshpande lab at Sanford Burnham Prebys, where she’s working to find better treatments for a blood cancer called acute myeloid leukemia (AML). We caught up with Barbosa Guerra as she prepares to take the virtual stage at the Diversity and Science Lecture Series at UC San Diego (DASL) to learn more about when she decided she wanted to be a scientist and where she can be found when not in the lab.

Tell us about the moment you realized you wanted to be a scientist.
According to my mother, I stated that I wanted to become a chemist to develop vaccines when I was ten years old. However, it wasn’t until middle school that I started cultivating my own sense of scientific curiosity. At that time, I was in a Girl Scouts program centered on HIV/AIDS peer education, so I began to read a bit more about viruses. It was incredibly amazing that they could linger undetected in our bodies—and that many questions about their biology remained unanswered. The more I learned, the less I felt I knew, and I wanted to follow that endless string of questions.

What do you study, and what is your greatest hope for your research?
I study a cancer called acute myeloid leukemia—specifically, subtypes that are hard to treat. Certain cancer cells, like stem cells, are pretty resilient and can self-renew. This enables them to resist therapy, so we want to discover better ways to target this particular feature. My research aims to find ways in which we can treat these leukemias based on their stem cell–like capabilities. My hope is that we can ultimately benefit the patients enduring harsh treatments and disease relapse, and along the way, illuminate the fascinating aspects of the biology behind effective treatments.

What do you wish people knew about science?
That it’s a team effort. The current coronavirus pandemic has really shown us that collaboration is at the heart of transformative science. I think that great ideas are best developed through discussion—and the thrill of putting the pieces together is way more enjoyable with company.

How do you think your lab colleagues would describe you?
Maybe as the girl with a bunch of notebooks. I like to make notes of everything. My notebooks are way more reliable than my memory.

What is the best career advice you’ve ever received?
Early in the graduate program, one of my mentors told me, “Be there,” meaning that I had to spend time with my science. If I were to discover something or make a great insight, I had to be there to do it, think it or see it.

What do you wish people knew about Sanford Burnham Prebys?
That this is such a welcoming community. I felt this the very first time I visited the campus, and I feel so at home here as a student. There are plenty of opportunities to engage with others and help each other out. I really enjoy the collaborative spirit of our little community.

Learn more about the Institute’s Graduate School of Biomedical Sciences.

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Meet computational biologist Mallika Iyer

AuthorMonica May
Date

January 14, 2021

Mallika Iyer in front of computer with green protein

Iyer is studying how proteins “dance,” which could lead to better drugs and a deeper understanding of human health 

DNA is often the star of the show when we talk about the body, but proteins are the true front-line workers. Formed by DNA’s instructions, proteins begin as strings of chemical compounds and later fold into a 3D shape that dictates their job in the body. If scientists can solve a protein’s shape—a feat that often takes years or decades—they may be able to create better drugs or better understand disease.  

Biologist Mallika Iyer, a graduate student in the Godzik lab at Sanford Burnham Prebys, is harnessing the power of computers to unlock insights into protein structure and movement. We caught up with Iyer as she prepares to take the virtual stage at DASL (the Diversity and Science Lecture Series at UC San Diego) to learn more about her greatest hopes for her research and what makes her tick.

Did you always know you wanted to be a scientist?
I’ve known I wanted to be a scientist ever since I learned about the digestive system as a kid. I was fascinated by how the human body works—it’s the most well-thought-out machine ever. 

I didn’t, however, imagine myself being a computational scientist until much later. When I was in college, I realized that traditional lab work wasn’t for me. I began learning some basic coding after I graduated and was hooked. That transitioned into computational biology/bioinformatics.

What do you study, and what is your greatest hope for your research?
I study protein structure and flexibility. Proteins are often depicted as having a single structure, but they are actually very flexible and transition between many different conformations as a part of their function—sort of like a well-choreographed dance.

My greatest hope for my research, or this field in general, is that we will someday be able to predict the types of movements a protein undergoes during the course of its function, or “job.” Last year, the field saw a huge advancement in the prediction of protein structure (read more in The New York Times). But “structure” is only half the story. Being able to predict all the different conformations and movements would be incredibly useful for medicine—and very cool!

What do you wish people knew about science?
That being wrong is a huge part of science. Scientists are supposed to understand and explain how the world works. But that is something that involves a lot of trial and error! Being wrong is, in fact, the way we advance our knowledge.

When you aren’t working, where can you be found? Where is your happy place?
Prior to the pandemic, my happy place was actually the climbing gym. I was introduced to indoor rock climbing about two years ago, and I instantly fell in love it with. It’s a great way to exercise both your body and mind, and I have found the climbing community to be really friendly and accepting. What makes my gym even better is that it also has extra space to just hang out, work, read a book, and so on. So, I used to go there a lot!

What is the best career advice you have ever received? 
Use every opportunity you can to present your work and network with people. I try to present at as many conferences and symposia as I can, and simultaneously use that as a way to meet and network with others in the field. I’ve found that this allows me to practice answering questions about my work, which in turn enables me to think more critically about it. And it can also lead to new opportunities that further my research and career.

What do you wish people knew about Sanford Burnham Prebys?
That it has a graduate program! I think our program is really unique. Its small size means that each student gets a lot of attention, and we have an Office of Education, Training and International Services (OETIS) that really offers us a lot of great resources to help us shape our careers.
 

A woman in workout clothes kneeling in front of a rock climbing wall

​Prior to the pandemic, Mallika’s happy place was the climbing gym. “It’s a great way to exercise both your body and mind, and I have found the climbing community to be really friendly and accepting,” she says.

Learn more about the Institute’s Graduate School of Biomedical Sciences.

Institute News

On the path to personalized breast cancer treatments

AuthorMonica May
Date

October 24, 2019

Fleet Cancer series-breast cancer

Ruth Claire Black wasn’t entirely surprised when she was diagnosed with breast cancer six and a half years ago. Her mother had died at age 52 of breast cancer, only two years after she was first diagnosed, Black explained at our recent Fleet Science Center event. New treatments have allowed Black’s story to differ from her mother’s—but as breast cancer experts from Sanford Burnham Prebys and UC San Diego Health explained, there is still a long way to go. 

“There is a great misconception that breast cancer is extremely easy to treat and is always cured. But the truth is that one in three women with early-stage breast cancer will relapse and eventually die from the disease,” said speaker Rebecca Shatsky, MD, a breast cancer oncologist at UC San Diego Health. “We are learning there aren’t one or two kinds of breast cancer—there are up to 30 different subtypes. To cure breast cancer, we need to look at treatments through a personalized lens.” 

Breast cancer is the second most common cancer in American women. One in eight women will be diagnosed with breast cancer in her lifetime, and more than 40,000 women die each year from the cancer. Targeted treatments—such as those that block the HER2 receptor—and hormone-based therapies have extended survival. However, 30% of people with estrogen-positive breast cancer, the most common form, eventually stop responding to standard-of-care treatments, for reasons that are largely unknown.

Speaker Svasti Haricharan, PhD, assistant professor at Sanford Burnham Prebys, is working to change these realities. Her work centers on a breast cancer subtype caused by defects in DNA repair machinery—a genomic “spell check” that normally corrects DNA copy errors during cell division. Nearly 20% of people who do not respond to breast cancer treatment have mutations in this machinery. Working with Shatsky, Haricharan’s team identifies breast cancer samples that have DNA damage repair defects. Then she tests these samples against thousands of FDA-approved treatments—with the goal of finding an effective treatment. 

For people like Black, these advances can’t come soon enough. 

“We have so much information about breast cancer. We have great diagnostics. Because of these tests, I know I’m a carrier of the BRCA2 mutation. I also know that it’s only a matter of time until my cancer returns,” said Black, who is a member of Sanford Burnham Prebys’ Community Advisory Board. “But doctors don’t know what to do with all of this information. That’s why I’m so supportive of the work taking place at Sanford Burnham Prebys. They are taking this information and doing something with it.” 

This event was the third of our five-part “Cornering Cancer” series. Register today to join us for discussions on pancreatic cancer in November and pediatric brain cancer in December. 
 

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Scientists discover new survival strategy for oxygen-starved pancreatic cancer cells

AuthorMonica May
Date

October 23, 2019

Cancer tumor

Oxygen is essential to life. When fast-growing tumor cells run out of oxygen, they quickly sprout new blood vessels to keep growing, a process called angiogenesis. 

By blocking pancreatic cancer’s oxygen-sensing machinery—the same field of research studied by the winners of the 2019 Nobel Prize in Medicine—Sanford Burnham Prebys scientists have uncovered a new way that tumors turn on angiogenesis in an animal model. The discovery, published in Cancer Research, could lead to a treatment that is given with an anti-angiogenetic medicine, thereby overcoming drug resistance. 

“Treatment resistance is a major challenge for cancer treatments that block blood vessel growth,” says Garth Powis, D.Phil., professor and director of Sanford Burnham Prebys’ National Cancer Institute (NCI)-designated Cancer Center and senior author of the study. “Our research identifies a new way angiogenesis is activated, opening new opportunities to find medicines that might make existing cancer treatments more effective.” 

Many cancer treatments work by blocking angiogenesis, which rarely occurs in healthy tissues. However, these medicines eventually stop working, and the cancer returns, sometimes in as little as two months. Scientists have been researching why this treatment resistance occurs so it can be stopped.

In this study, the scientists focused on pancreatic cancer, which is notoriously desperate for oxygen and also difficult to treat. Fewer than 10% of people diagnosed with pancreatic cancer are alive five years later. 

To see how a pancreatic tumor responds to a disruption in its oxygen supply, the Sanford Burnham Prebys researchers used a mouse model to block an oxygen-sensing protein called HIF1A—which should cripple the tumor’s growth. Instead of dying, however, after about a month the cells multiplied—indicating they had developed a new way to obtain oxygen. 

Further work revealed that the cancer cells were clear and swollen with the nutrient glycogen (a characteristic also seen in some ovarian and kidney cancers). In response to the excess glycogen, special immune system cells were summoned to the tumor, resulting in blood vessel formation and tumor survival. Each of these responses represents a new way scientists could stop pancreatic tumors from evolving resistance to treatment.

“Our team’s next step is to test tumor samples from people with pancreatic cancer to confirm this escape mechanism occurs in a clinical setting,” says Powis. “One day, perhaps we can create a second medicine that keeps anti-angiogenic drugs working and helps more people survive pancreatic cancer.”

Research reported in this press release was supported by the U.S. National Institutes of Health (NIH) (5F31CA203286, CA216424 and P30CA030199). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The study’s DOI is 10.1158/0008-5472.CAN-18-2994. 

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Sanford Burnham Prebys welcomes U.S. Congressman Mike Levin

AuthorMonica May
Date

October 22, 2019

Congressman Mike Levin visits SBP

On October 1, 2019, U.S. Representative Mike Levin (D-CA) toured Sanford Burnham Prebys and met with several faculty members to learn more about the innovative biomedical research taking place in his backyard. Levin represents California’s 49th Congressional District, which includes North County San Diego, South Orange County and neighbors our La Jolla campus. 

The visit kicked off with a visit to a lab working to find medicines for a heart arrhythmia condition called atrial fibrillation (AFib), a disorder that hits home for Levin: His grandmother struggled with the disease. Levin peered into a microscope to view beating heart cells and learned how a team of experts from Sanford Burnham Prebys and Scripps Clinic are working to develop personalized treatments for the condition, which affects nearly six million Americans (meet the A-team.)

“Sanford Burnham Prebys is a great example of the vibrant biomedical research taking place in San Diego that has the potential to improve the quality of life for families across the country,” says Levin. “Seeing the Institute’s critical research up close and hearing firsthand how National Institutes of Health (NIH) funding has accelerated medical discovery only strengthens my commitment to supporting biomedical science. Following my visit to Sanford Burnham Prebys, I was proud to introduce legislation that would invest $10 billion in the NIH to support biomedical research, and I will continue to fight for this much-needed funding.”

Following the lab tour, Levin met with faculty members who—thanks to federally funded research—are working to find treatments for Alzheimer’s disease and addiction, and study the aging process to address age-related diseases such as cancer. The visit wrapped up in the lab of Hudson Freeze, PhD, the director of our Human Genetics Program, who studies a rare childhood disease called congenital disorders of glycosylation, or CDG. 

“Americans today are living longer and healthier lives because of federally funded medical research,” says Chris Larson, PhD, the adjunct associate professor of Development, Aging and Regeneration at the Institute who arranged the visit. “We are grateful that Mike took the time to sit down with us to learn about our NIH-funded work and how he can help support us on our mission to find cures for human disease.”

Editor’s note: Shortly after his visit Levin introduced legislation that calls for a $10 billion investment in biomedical research.