Top Stories - Tumor Development

Cerebellar stem cells normally generate neurons (green), astrocytes (blue) and oligodendrocytes (red), but can also give rise to brain tumors. (Image courtesy of the Wechsler-Reya lab)
In cancer, context is...

Dr. Robert Wechsler-Reya talks about his work on medulloblastoma and explains how mechanisms that...

Cerebellar stem cells engineered to express Myc and mutant p53 (shown here) give rise to aggressive tumors that resemble a particularly malignant form of human medulloblastoma, providing a new model that will help scientists develop more effective therapies for this disease.
New model of childhood brain...

Sanford-Burnham researchers create a new mouse model for a particularly malignant form of...

Dr. Robert Wechsler-Reya
New insights into...

San Diego’s Rady Children’s Hospital recently brought together an all-star cast of speakers for...

Meet a cancer researcher: Robert Wechsler-Reya

by on March 30, 2012 at 7:36 am | 0 Comments
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Dr. Wecshler-Reya and his family

Dr. Wecshler-Reya and his family

On June 5, 2012, California voters will have an opportunity to consider Proposition 29, also known as the California Cancer Research Act. Prop 29’s goal is to provide funding for cancer research by increasing the tax on a pack of cigarettes by $1. Sanford-Burnham’s Board of Trustees endorsed Prop 29 in September 2011. The University of California Regents has also voted to support it, along with the American Cancer Society, American Lung Association, American Heart Association, Stand Up To Cancer, and the Lance Armstrong Foundation (Livestrong).

We are presenting a series of blog posts to allow you to meet some of our cancer researchers and gain a better understanding of how the projected $735 million generated annually by the passing of Prop 29 would benefit cancer research in California.

Meet Robert Wechsler-Reya, Ph.D., director of the Tumor Development Program in Sanford-Burnham’s NCI-designated Cancer Center.

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New model of childhood brain cancer establishes first step to personalized treatment

by on February 13, 2012 at 9:01 am | 4 Comments
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Cerebellar stem cells engineered to express Myc and mutant p53 (shown here) give rise to aggressive tumors that resemble a particularly malignant form of human medulloblastoma, providing a new model that will help scientists develop more effective therapies for this disease.

Cerebellar stem cells engineered to express Myc and mutant p53 (shown here) give rise to aggressive tumors that resemble a particularly malignant form of human medulloblastoma, providing a new model that will help scientists develop more effective therapies for this disease.

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.

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Coming soon: Medscape’s “Developments to Watch”

by on July 1, 2011 at 7:08 am | 0 Comments
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Dr. Evan Snyder (right) interviews his colleague, Dr. Steven Smith, on the Medscape set.

Dr. Evan Snyder interviews his colleague, Dr. Steven Smith, on the Medscape set.

Last week, Sanford-Burnham’s Fishman Auditorium, on the Institute’s La Jolla campus, was transformed into a temporary television studio. It was hardly recognizable under the bright lights and set dressing. Medical website Medscape recorded interviews with three Sanford-Burnham researchers for a new video series called “Developments to Watch.” The talk show-like discussions were hosted by Dr. Evan Snyder, who directs the Stem Cells and Regenerative Biology Program at Sanford-Burnham. Dr. Snyder is both a medical doctor who regularly sees patients and a scientist who conducts research in his own lab – the perfect person to help explain how discoveries made today might one day help patients.

Medscape is part of the network of sites run by WebMD. With this newest video series, Sanford-Burnham scientists will be providing expert commentary and information to help keep Medscape’s audience – primary care physicians, specialists and other health professionals – up-to-date on the latest medical research and what it means for their patients.

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Glioblastoma’s skeletons in the closet

by on June 7, 2011 at 10:15 am | 0 Comments
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Drs. Robert Margolis, Rati Fotedar and Andreas Panopoulos

Drs. Robert Margolis, Rati Fotedar and Andreas Panopoulos

Even if you’re sitting very still, some of your cells might be on the move, especially if your body is fighting an infection or healing a wound. Cells do this by rearranging their cytoskeletons, the framework that gives cells their shape. The problem is when cancer cells move – damaging an entire organ or metastasizing to distant sites in the body.Two protein networks make up the cytoskeleton and allow for cellular movement – actin and microtubules. Actin is the major driver, while microtubules play a secondary role as navigator. However, a recent study led by Dr. Robert Margolis challenges that accepted dogma. He and his team found that glioblastoma cells, a type of brain cancer, are the exception to the rule. To Dr. Margolis’ surprise, glioblastoma cell movement persists even when the actin scaffolding is completely disassembled.

 “This still needs to be confirmed, but something unusual is definitely happening,” explains Dr. Margolis, professor in Sanford-Burnham’s Tumor Development Program. “This is very atypical behavior for cells.”

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In cancer, context is everything

by on May 9, 2011 at 6:00 am | 3 Comments
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Cerebellar stem cells normally generate neurons (green), astrocytes (blue) and oligodendrocytes (red), but can also give rise to brain tumors. (Image courtesy of the Wechsler-Reya lab)

Neurosphere

May is National Cancer Research Month, created by Congress in 2007 to recognize the American Association of Cancer Research (AACR) for its contributions to the field. To honor AACR and highlight some of the important cancer research being done at Sanford-Burnham, we will be posting a series of articles on the ongoing work in our National Cancer Institute-designated Cancer Center. The vast majority of this research is made possible by funding from the National Institutes of Health (NIH), which includes the National Cancer Institute (NCI).

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.”

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Tales from the intestinal crypt

by on April 14, 2011 at 7:46 am | 0 Comments
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Cells proliferating in an intestinal crypt (blue) (Image courtesy of the Oshima lab)

Cells proliferating in an intestinal crypt (blue) (Image courtesy of the Oshima lab)

Doctors have noticed for decades that people with Down Syndrome seldom develop cancers. Down Syndrome results from an extra copy of chromosome 21, leading scientists to wonder if something about that particular piece of the genome could protect against cancer. A few years ago, researchers at Johns Hopkins University tested that hypothesis. They added several different chromosome fragments from the mouse equivalent of human chromosome 21 to mice that are susceptible to colon tumors until they narrowed down its protective effect to just 33 genes– including one called Ets2.Meanwhile, Dr. Robert Oshima and his team were already studying Ets2 and its role in breast cancer, where Ets2 does the opposite – it promotes tumor formation. Intrigued by the new and seemingly paradoxical findings in colon cancer, they started looking at mice bred to lack Ets2 only in intestinal cells.

“Our initial results were the complete opposite of what we expected,” says Dr. Jorge Múnera, former graduate student in the Oshima lab and now postdoctoral researcher in Dr. Hudson Freeze’s group. “Unlike what we saw in our breast cancer model, Ets2-deficient mice clearly had more colon tumors.”

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Got MELK?

by on January 19, 2011 at 2:51 pm | 3 Comments
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Not all cells in a tumor are equal. They have different genes, proteins and behaviors and while some are easily killed, others are more resistant to cell-destroying therapies. In some cancers, a few of these hardier cells are cancer stem cells and they may be the culprits behind tumor formation and drug resistance. Much like other types of stem cells, cancer stem cells can do two things: self-renew (generating more new stem cells) and differentiate (giving rise to a variety of cell types). The trick to better understanding tumor formation, and designing drugs that specifically target cancer at its root, is figuring out how to pick the stem cell needle out of the tumor haystack. Drs. Alexey Terskikh and Robert Oshima think a protein called MELK, short for maternal embryonic leucine zipper kinase, might allow them to do just that.Dr. Terskikh has studied MELK for almost 10 years, but it hasn’t been easy. Early on,  researchers would disrupt MELK in mice but see no consequences from that disruption. Now, in a recent paper published in the journal Cancer Research, Dr. Terskikh, Dr. Oshima, and their colleagues show that MELK protein levels are particularly high in tumor-initiating cells found in a mouse model of breast cancer.

“Previous studies provided evidence that high MELK levels correlate with poor prognosis in breast and brain tumors,” Dr. Terskikh says. “Now we show for the first time that MELK does actually play a role in mammary tumor initiation and progression in a relevant animal model of breast cancer.”

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New insights into children’s health

by on November 22, 2010 at 10:54 am | 2 Comments
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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.

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Differentiation therapy: a different approach to treating tumors

by on September 6, 2010 at 3:00 pm | 9 Comments
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What if the best way to stop a tumor is not to kill it, but to turn it into something else? That’s the idea behind differentiation therapy, a novel concept that targets cancer stem cells. Scientists at Sanford-Burnham and elsewhere are beginning to think that stem cells may be the culprit behind tumor formation in some cancers. Much like other types of stem cells, cancer stem cells are presumably able to do two things: 1) self-renew, generating more new stem cells and 2) differentiate, giving rise to a variety of cell types. Differentiation therapy attempts to end the cycle of self-renewal by encouraging the cells to settle down and become a specific cell type, such as a skin cell.

“It seems to me that if we are smart enough to know all the genes in a cell, we should be smart enough to tell the cell what to do,” says Dr. Robert Oshima, co-director of the Sanford-Burnham Cancer Center’s Tumor Development Program. “In differentiation therapy, we are essentially telling cells: ‘Don’t become criminals, become productive members of society. If you stay legal, we’ll leave you alone.’”

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Institute Welcomes Robert Wechsler-Reya

by on August 5, 2010 at 8:57 am | 2 Comments
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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.

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A Coming Together of Cancer Centers

by on August 4, 2010 at 9:35 am | 0 Comments
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A group of top researchers from the University of Texas MD Anderson Cancer Center (MDACC) gathered with their Sanford-Burnham counterparts in La Jolla last week to seek ways the two Cancer Centers could collaborate to translate basic research into new medicines.

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A pain reliever that does it all

by on June 14, 2010 at 9:31 am | 2 Comments
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Many studies have shown that a daily dose of aspirin can help prevent cancer. Now Sanford-Burnham scientists Dr. Xiao-kun Zhang, Dr. Hu Zhou and others have found a way to block tumor growth by using a related pain reliever called Sulindac. The study, published in the June 15, 2010 issue of the journal Cancer Cell, pieced together the molecular mechanism Sulindac uses to destroy cancer cells, and created a new-and-improved version of Sulindac that does an even better job of it.

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