May is National Cancer Research Month, so we thought we’d highlight exciting cancer research underway at Sanford-Burnham. Today, we focus on a few of the strategies our researchers are pursuing to better understand the pathologies of cancer tumors—and stop them in their tracks.
Napoleone Ferrara, Ph.D., was propelled into the national spotlight last week, when he was named one of 11 winners of the first Breakthrough Prizes in Life Sciences. This new prize—awarding a no-strings-attached $3 million to each recipient—was bestowed by Silicon Valley innovators Sergey Brin, Anne Wojcicki, Mark Zuckerberg and Yuri Milner. One goal of the prize is to make household names out of the country’s top scientists.
Brain tumors arising from different cell types might require different—and more personalized—treatment approaches.
Cancers arise when a normal cell acquires a mutation in a gene that regulates cellular growth or survival. But the particular cell this mutation happens in—the cell of origin—can have an enormous impact on the behavior of the tumor, and on the strategies used to treat it.
Robert Wechsler-Reya, Ph.D., professor and director of the Tumor Development Program in Sanford-Burnham’s NCI-designated Cancer Center, and his team study medulloblastoma, the most common malignant brain cancer in children. A few years ago, they made an important discovery: medulloblastoma can originate from one of two cell types: 1) stem cells, which can make all the different cell types in the brain or 2) neuronal progenitor cells, which can only make neurons.
Stem cells and progenitor cells are regulated by different growth factors. So, Wechsler-Reya thought, maybe the tumors arising from these cells respond differently to different therapies…
Congratulations to John B. Gurdon and Shinya Yamanaka on winning the 2012 Nobel Prize in Physiology or Medicine! They received the award today for their “discovery that mature cells can be reprogrammed to become pluripotent.” In other words, these scientists figured out how to turn a normal adult cell, such as a skin cell, into a stem cell that has the potential to become any other type of cell in the body. Read below to learn more about stem cells and how they are revolutionizing medical research.
What are stem cells?
Stem cells are special because each is like a blank slate. Once it’s given the proper instruction, a stem cell can specialize and become any type of cell in the body—brain, heart, muscle, and more. Stem cells also have the ability to reproduce themselves indefinitely, renewing the supply.
Are there different types of stem cells?
Embryonic stem cells only exist during an organism’s development, when it is an embryo. These cells are pluripotent, meaning they have the capacity to become any cell type in the body.
Adult stem cells exist in fully developed organisms. They are more limited than embryonic stem cells—they are multipotent rather than pluripotent. These stem cells usually can only become a few types of specialized cells, based on the tissue from which they originate.
Induced pluripotent stem cells (iPSCs) are pluripotent, much like embryonic stem cells. iPSCs are produced in the laboratory by genetically reprogramming any adult cell, such as a skin cell.
Where do new medicines come from? The first step in the drug discovery process often involves screening small molecules (chemicals) to determine their potential to produce innovative biological research tools. Sanford-Burnham’s Conrad Prebys Center for Chemical Genomics uses robotic technology to sift through chemical compounds by the millions to find the few that could potentially be developed into new medicines
Children with a devastating brain cancer called medulloblastoma develop tumors in a region of the brain called the cerebellum, which plays an important role in motor control. Seventy-five percent of children with the disease survive after aggressive surgery, radiation, and chemotherapy—but side effects can be severe, leading to cognitive deficits, endocrine disorders, and the development of other cancers later in life.
Sanford-Burnham scientists have now developed a new mouse model for studying medulloblastoma. The animal model mimics the deadliest of four subtypes of the human disease, a tumor that is triggered by elevated levels of a gene known as Myc. The study, published February 13 in the journal Cancer Cell, also suggests a potential strategy for inhibiting the growth of this tumor type. This achievement marks an important milestone toward personalized therapies tailored to a specific type of medulloblastoma.
“Being able to use an animal model as a tool to test treatments has been very valuable in medulloblastoma, as in other types of tumors. But for Myc-associated tumors, that hasn’t been an option because there hasn’t been a model of the disease. This is the first step to developing therapies for this type of tumor,” said Robert Wechsler-Reya, Ph.D., director of the Tumor Development Program in Sanford-Burnham’s National Cancer Institute-designated Cancer Center, member of the Sanford Consortium for Regenerative Medicine, and senior author of the study.
“Patient advocates: this is our day!” Lorraine Stiehl shouted, rallying the crowed assembled on November 29 to witness the grand opening of the Sanford Consortium for Regenerative Medicine, a new 150,000 square-foot, state-of-the-art research facility located in the Torrey Pines Mesa life science research cluster in La Jolla, a northern coastal area of San Diego, Calif.
Ms. Stiehl is a patient advocate coordinator for the California Institute for Regenerative Medicine (CIRM), the $3 billion stem cell agency created after California voters approved ballot measure Prop 71 in 2004. CIRM, and patient advocates like Ms. Stiehl, have played a huge role in bringing the Sanford Consortium to fruition. CIRM contributed $43 million to the project and patients are the reason that the consortium’s scientists are doing what they do—working to advance our understanding of stem cell biology and ultimately find new treatments for Alzheimer’s disease, diabetes, and many other conditions.
“You see 150,00 square feet of new research space,” Ms. Stiehl continued. “We see 150,000 square feet of hope, 150,000 square feet of empowerment.”
When The Atlantic magazine was looking for a location to host its first West Coast symposium, the Torrey Pines Mesa area of San Diego sprang to their attention. As Atlantic Vice President Elizabeth Baker Keffer wrote in her welcome, “The research hub of San Diego makes this the perfect location to experience the interdisciplinary experiments occurring on the front line of discovery.” They partnered with UC San Diego to present The Atlantic Meets the Pacific, October 17-19.
Sanford-Burnham joined The Scripps Research Institute, the Salk Institute, Scripps Institution of Oceanography, and UC San Diego’s Calit2 and Moores Cancer Center in representing the powerhouse of scientific ideas that resides here overlooking the Pacific Ocean.
Context can change everything. Driving 65 miles per hour on the highway is perfectly fine, but the same speed in a neighborhood could be deadly. The same is true in biology. Processes that are necessary in one context can be harmful in another.
Dr. Robert Wechsler-Reya, who directs the Tumor Development Program in Sanford-Burnham’s Cancer Center, has spent many years studying how “good” processes can also cause disease. He is particularly interested in how mechanisms that are normal in embryonic development can cause cancer when turned on in children and adults.
“We work on the relationship between development and cancer, particularly in the brain,” says Dr. Wechsler-Reya. “We’re interested in how normal stem cells and progenitor cells make decisions like when to divide, when to differentiate and what to differentiate into. We’re interested in how those decisions go wrong in cancer.”
Conventional medical care generalizes treatment to all patients with a particular disease. But since a disease is as individual as the person who has it, casting a wide therapeutic net has its limitations. For one, patients with a certain genetic makeup might not respond to a particular drug as well as patients with different genetics, or they might experience different side effects. As personalized medicine becomes a reality, it could rectify these less-than-ideal situations.
From the diagnostic point-of-view, personalized medicine is a shift from reactive to proactive. Based on a person’s health, genetic, and environmental profiles, doctors practicing personalized medicine could assess a patient’s risk for acquiring a genetic disease before any symptoms develop. This might allow them to target the specific genes that account for illness (the BRCA1/BRCA2 genes that predispose a woman to breast cancer, for example), incorporate a prevention strategy, and monitor those genes over time. When it comes to treatment, personalized drugs could be prescribed based on an individual’s molecular “build” and targeting treatment where it will do the most good and the least harm.
San Diego’s Rady Children’s Hospital recently brought together an all-star cast of speakers for a symposiumon pediatric translational research – laboratory research that could be “translated” into therapies for sick children. This was the ideal place to bring laboratory scientists together with physicians. The close connection to patients was clear, as kids played in the hall outside the conference room, paramedics checked out the posters and doctors used the wall phones to return pager calls and provide consultations.What did they talk about? A little bit of everything that’s hot in pediatric research: brain cancer, leukemia, rare genetic diseases, stem cell therapies and re-wiring the immune response to fight disease.
One of Sanford-Burnham’s newest recruits, stem cell expert Dr. Robert Wechsler-Reya, was there. Dr. Wechsler-Reya hasn’t finished his move to San Diego yet, but he did not want to miss the opportunity to connect with his colleagues in stem cell research and pediatric medicine.
Dr. Robert Wechsler-Reya, a well-known researcher at Duke University has accepted a faculty position at Sanford-Burnham. He will be a professor and director of the Tumor Development Program at the Institute’s NCI-designated Cancer Center. Dr. Wechsler-Reya is the first researcher to receive a Leadership Award from the California Institute for Regenerative Medicine (CIRM). The award, which will provide $5.9 million to support his research, was created to recruit stem cell scientists to California institutions.