San Diego is a powerhouse for cancer research, home to two National Cancer Institute (NCI)-designated centers for basic research—our Cancer Center and the Salk Institute Cancer Center—and the University of California, San Diego Moores Cancer Center, the region’s only NCI-designated comprehensive cancer center.
Potential cancer drug sabutoclax blocks Bcl-2 protein family members that help keep cancer cells alive. This image shows the structure of one Bcl-2 protein, known as Bcl-Xl. (Image courtesy of the Pellecchia laboratory)
Researchers find that certain types of drug-resistant leukemia stem cells are vulnerable to sabutoclax, a novel cancer stem cell-targeting drug based on Sanford-Burnham research.
New experiments show that sabutoclax, a novel cancer stem cell-targeting drug that grew out of research at Sanford-Burnham Medical Research Institute, in combination with other therapies, could effectively treat diseases like chronic myeloid leukemia (CML). Sabutoclax might also lower the chance of relapse.
“The demonstration of sabutoclax’s preclinical activity in mouse models of CML is exciting and encourages further evaluation of this promising drug candidate for aggressive leukemias. We look forward to continuing our collaborative studies of sabutoclax, as we move this drug closer to the clinic,” said John Reed, M.D., Ph.D., professor and Donald Bren Chief Executive Chair at Sanford-Burnham.
Sabutoclax was first discovered as a result of research in the laboratories of Reed and his Sanford-Burnham colleague, Maurizio Pellecchia, Ph.D. The pair is now working with biotechnology company Oncothyreon Inc to develop sabutoclax into a potential anti-cancer drug. This latest study of sabutoclax’s efficacy, published January 17 in the journal Cell Stem Cell, was led by Catriona Jamieson, M.D., Ph.D., at UC San Diego Moores Cancer Center, in collaboration with Reed, Pellecchia and others.
Sanford-Burnham benefactor Malin Burnham, Sanford-Burnham President, Kristiina Vuori, M.D., Ph.D., Pradeep K. Khosla, and Sanford-Burnham CEO John Reed, M.D., Ph.D.
The location of Sanford-Burnham’s headquarters on the Torrey Pines Mesa of La Jolla, Calif., puts us squarely at the center of a hive of innovation. Part of our innovative spirit means we engage in constant dialogue with other, nearby scientific institutions. So when Pradeep K. Khosla, who took up the mantle of Chancellor at UC San Diego on August 1, expressed a desire to get acquainted with his new neighbors, we welcomed him.
Earlier this week, Khosla travelled just across the street to meet with Sanford-Burnham leadership and to tour the Conrad Prebys Center for Chemical Genomics. He was amazed with the state-of-the-art robotic screening center.
Khosla has expressed his commitment to innovation as a means of bringing income to UC San Diego, and to the region. In fact, a writer for the UT San Diego recently said of Khosla’s arrival in town, “The San Diego entrepreneur community should pay close attention.”
Conventional therapies don't hit tumors in the right place - at the cancer stem cells - so they keep coming back
The scientific symposium portion of San Diego’s annual Stem Cell Meeting on the Mesa fell on Halloween this year—good timing for a discussion about the dark side of stem cells: cancer stem cells.
Robert Wechsler-Reya, Ph.D., director of Sanford-Burnham’s Tumor Development Program, once said, “Current cancer therapies are like trying to kill a zombie by kicking it in the shins.”
Everyone knows you can only kill a zombie with a shot to the brains—anywhere else might slow it down temporarily, but only a very targeted hit to the head will get rid of it for good. (See the CDC’s Zombie Preparedness Guide.) So what Wechsler-Reya means is that the current methods for destroying or removing tumor cells are not aimed at what may, in some cases, be the actual “brains” of the problem—cancer stem cells.
Like other types of stem cells, cancer stem cells can self-renew, producing more cells. They also differentiate, specializing into other cell types. Those are very useful features when scientists are using stem cells to repair or replace diseased or damaged tissue (rebuilding heart muscle tissue after a heart attack, for example). However, cellular proliferation is also a hallmark of cancer.
In some cancers, stem cells may be the initial source of the problem, giving rise to tumors. They might also be the reason some tumors are resistant to standard cancer therapies such as chemotherapy or radiation therapy. What’s more, cancer stem cells can allow tumors to recur—even if the bulk of a tumor is removed, a few remaining cancer stem cells rise up to rebuild a new tumor. Like zombies, they are hard to get rid of.
Scientists are now trying to learn how stem cells turn to the dark side in cancer so that they can figure out how to better detect, prevent, and treat tumor growth—targeting the zombie’s brains, not just its shins.
Meet the four cancer stem cell (zombie)-fighting scientists who spoke at the 2012 Stem Cell Meeting on the Mesa:
Protein structures, like these from the bacterium Thermotoga maritima, help us understand both the form and function of protein networks.
Whether online or in print, a scientific paper typically winds up sandwiched between two equally important – but completely unrelated – articles. But a scientific journal called Acta Crystallographica Section F recently did something completely different. They ran an issue entirely devoted to research from a single group – the Joint Center for Structural Genomics (JCSG), one of the NIH’s Protein Structure Initiative centers. JCSG is led by Dr. Ian Wilson at The Scripps Research Institute, with Dr. John Wooley at UC San Diego and Sanford-Burnham’s Dr. Adam Godzik leading the bioinformatics and data management part of the project.It’s unusual for a journal to dedicate an entire issue (35 papers total) to one research group, but that’s not the only thing that made this unique.
Cocaine produces its powerful high by stimulating “reward” signals in the brain, sending users back again and again for more. Cocaine gains this effect, in part, by stimulating a receptor called the metabotropic glutamate receptor 2 (mGluR2). Dr. Nicholas Cosford’s group is currently collaborating with Dr. Athina Markou at UC San Diego and Dr. P. Jeffrey Conn at Vanderbilt University Medical Center to design chemical compounds that bind mGluR2 in a way that dampens cocaine’s stimulatory effects on the brain. The team recently found that, when given to rats, one such compound – called BINA – reduces cocaine-seeking behavior and consumption.
New treatments for drug addiction are clearly needed. Cocaine is responsible for more emergency room visits in the United States than any other illegal drug. It harms the brain, heart, blood vessels and lungs, and can even cause sudden death. With an estimated two million addicts in this country, cocaine is a major public health issue.
Yet a deeper understanding of mGluR2 might have an even greater impact on human health.
We can’t wait for our newest neighbor to open its doors! The Sanford Consortium for Regenerative Medicine is scheduled to complete construction on its research building in June. Check out this live video feed of the building taking shape right around the corner from Sanford-Burnham’s La Jolla campus.
The Sanford Consortium, a collaboration between Sanford-Burnham, the Salk Institute for Biological Studies, The Scripps Research Institute and UC San Diego, was created to combine the talent and technology of these four great research institutions to advance our understanding of stem cell biology and ultimately find new treatments for Alzheimer’s disease, Parkinson’s disease, diabetes, paralysis and many other conditions. The building is being funded largely through a $30 million gift from T. Denny Sanford and a $43 million grant from the California Institute for Regenerative Medicine (CIRM).
A collaborative team led by Dr. Gabriel Haddad at the University of California, San Diego (UCSD), which includes Sanford-Burnham’s Dr. Rolf Bodmer, Dr. Pilar Ruiz-Lozano, Dr. Karen Ocorr and Dr. Giovanni Paternostro, was awarded a $10 million grant from the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. The team will research the molecular response to low oxygen levels – a condition known as hypoxia– in heart, lung and brain cells.
“This funding will allow us to develop powerful predictions of how the human heart and other organs can be protected from hypoxia-inflicted injury by studying both fruit flies, which are very tolerant to low oxygen, and mice, which are less tolerant,” explains Dr. Bodmer, professor and director of Sanford-Burnham’s Development and Aging Program.
According to Dr. Paternostro, adjunct assistant professor, ”This grant will allow us to continue our work on the systems biology and metabolomics of hypoxia, an ongoing collaboration with Dr. Haddad and with the other scientists participating in the funded project.”
On May 14, UC Irvine opened the first of seven California Institute for Regenerative Medicine (CIRM) institutes. The 85,000-square-foot Sue and Bill Gross Stem Cell Research Center will feature a basic research program to explore new methods to isolate stem cellsand understand their fundamental properties; a drug discovery program to identify and develop stem cell-based therapies; and a regenerative medicine application program to study the efficacy and safety of new therapies and bring them to the clinic. The research will focus on Alzheimer’s disease, spinal cord injuries and macular degeneration.San Diego has our own CIRM Institute on the horizon. On March 26, the Sanford Consortium for Regenerative Medicine held the official groundbreaking ceremony for its new 135,000-square-foot research building on Torrey Pines Mesa. The Consortium, a collaboration between Sanford-Burnham, the Salk Institute, The Scripps Research Institute and the University of California, San Diego, was created to combine the talent and technology of these four great research institutions to advance our understanding of stem cell biology and ultimately find new treatments for Alzheimer’s disease, Parkinson’s disease, diabetes, paralysis and many other conditions. The building is being funded largely through a $30 million gift from T. Denny Sanford and a $43 million grant from CIRM. The facility is expect to open in June 2011.