Searching for new cancer drugs: Part 2

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Yesterday, we introduced a study in which scientists in Sanford-Burnham’s NCI-Designated Cancer Center and Conrad Prebys Center for Chemical Genomics were looking for compounds that regulate invadopodia, cellular projections that allow cancer cells to invade and metastasize. They used robotic technology and automated microscopy to screen a library of pharmacologically active compounds—compounds already known to influence cellular function. In the course of the study, the researchers found some compounds that inhibit invadopodia and some that promote their formation. One of the latter was paclitaxel. Paclitaxel, also known by the brand name Taxol, is an FDA-approved drug currently used to treat several different kinds of cancer. The drug’s anti-tumor activity is based on its ability to bind and stabilize microtubules, one component of the cellular cytoskeleton, thereby halting cell division and inducing cellular suicide (a good thing, for cancer).

Battling metastasis

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Metastasis is a word no one wants to hear. Cells that should never leave their biological home migrate to distant parts of the body. Many things have to go wrong with cellular checks and balances for this to happen, yet it happens all too frequently.

To metastasize, cells must acquire a number of properties, including the abilities to move, survive in the bloodstream, cross tissue boundaries and grow in foreign organs. These last two properties require the activity of proteases, enzymatic proteins that break down other proteins. Dr. Sara Courtneidge, director of Sanford-Burnham’s Tumor Microenvironment Program, studies how the activity of these proteases is controlled by cell surface structures called invadopodia. These finger-like projections from the cell membrane are found in metastatic cancer cells but not in non-invasive cells. Dr. Courtneidge’s laboratory discovered a protein, called Tks5, which controls the formation of these invadopodia in cancer cells.

Tumors Beware, Part 2

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Last week we mentioned a lecture Dr. Kristiina Vuori, Sanford-Burnham’s president and director of our NCI-Designated Cancer Center, gave to San Diego’s CONNECTcommunity about the Institute’s many exciting advances in cancer research.So how exactly do Sanford-Burnham researchers put cancer cells in their place?

As Dr. Vuori highlighted in her lecture, scientists in each of Sanford-Burnham Cancer Center’s four programs – Tumor Development, Signal Transduction, Tumor Microenvironment and Apoptosis and Cell Death Research –  are designing new therapies that tackle cancer during every step of the disease’s progression. Here are just a few examples of Sanford-Burnham’s multi-pronged approach, as described by Dr. Vuori…

A Coming Together of Cancer Centers

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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.

Learning How Cancer Works

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The more strategies we adopt in the war on cancer, the more opportunities we will have to develop new medicines. Here’s how Sanford-Burnham scientists approach the fight…

Targeting prostate tumors with nanoworms

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One way to inhibit a tumor’s growth is to choke off its blood supply. The trick is to create a clot that specifically blocks flow to the tumor without harming other parts of the body. To accomplish this, a research team led by Dr. Erkki Ruoslahti, distinguished professor and founding member of the U.C. Santa Barbara – Sanford-Burnham Center for Nanomedicine, coated nanoparticles with two different homing signals that specifically direct them to proteins on tumor blood vessels. One signal was generated by a string of just five amino acids(the molecular subunits that make up a protein), while the other consisted of six amino acids. These two types of targeted nanoparticles worked cooperatively to induce blood clots, and an elongated version of these particles, called “nanoworms,” did an even better job of it. As the nanoworms induced clotting, more and more binding sites appeared, attracting more nanoworms and further enhancing the blockage.

Influenza and nanomachines

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Drs. Sumit Chanda and Erkki Ruoslahti have received write-ups at two very distinct sites. Dr. Chanda’s flu research, which was published in February in Nature, was recently highlighted by the National Institute of Allergy and Infectious Disease, one of the National Institutes of Health. The work, a collaboration with Mount Sinai , Salk and GNF, identified 295 human proteins and other molecules  that influenza A strains must harness to infect a cell.  As the article points out,  the flu virus contains only 11 proteinsand must rely on our own cellular machinery to keep going. In many ways, these host factors may be better targets for treatment.

Current flu drugs are aimed directly at the influenza virus. But the flu virus mutates readily and these frequent changes allow it to gain resistance to antiviral drugs. However, if a drug were to be targeted to factor in the human host instead of being aimed directly at the virus, the pathogen’s ability to escape through mutation would be thwarted.

Meanwhile, Dr. Ruoslahti, who cofounded the Sanford-Burnham, UC Santa Barbara Center for Nanomedicine, was quoted in an article about robots at CNBC. Dr. Ruoslahti has been working with engineers at UC Santa Barbara to create nanorobots to home in on diseased cells.

“At this point, we can increase the activity of any anticancer drug by three fold or better,” he says. “We get more drug to the tumor and that makes a huge difference. If you can increase its concentration, the side effects remain the same, but the effectiveness is higher.”

Embracing Nanomedicine, Part 3

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One of the main reasons Drs. Erkki Ruoslahti and Jamey Marth set up labs at UC Santa Barbara was to take advantage of the university’s world-class expertise in engineering.“Because of my knowledge of homing peptides, engineers began approaching me about using this technology to help target nanoparticles,” says Dr. Ruoslahti. “I realized that molecular biology and chemistry have made great contributions to medicine, but we needed to do more. It was time to also focus on physics.”

Embracing Nanomedicine, Part 2

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Sanford-Burnham Distinguished Professor Erkki Ruoslahti, M.D., Ph.D., sits in his office at UC Santa Barbara and ponders the relationship between science and science fiction. He is discussing Star Trek’s sophisticated hand-held medical devices and all they could do for patients.

“Ideally, you would like to have a device like Dr. McCoy’s that could both diagnose and treat,” says Dr. Ruoslahti. “I think eventually we will have devices like small MRI machines that can do just that.”

Embracing nanomedicine, part 1

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Jamey Marth, Ph.D.,who directs the joint Center for Nanomedicine established by Sanford-Burnham and UC Santa Barbara, began his career studying genes. In fact, he helped develop Cre-loxP technology, which is used by researchers worldwide to selectively remove genes to study their functions in specific cells and tissues at specific times. But over time, Dr. Marth realized that there was more to cells than what DNA, RNA and proteins were teaching us.

“We have been looking to genes to find the origins of disease,” says Dr. Marth, “but genomic variation has not explained the origins of many common grievous diseases, such as diabetes, autoimmune conditions and various neurodegenerative disorders.”

On the Cover of Science

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Dr. Erkki Ruoslahti’spaper on iRGD, a peptide that helps a variety of anti-cancer drugs penetrate tumors, is the cover story for the most recent edition of the journal Science. The research was previously published online on April 8. Normally, we wouldn’t revisit this, but the cover of Science is a pretty big deal. Kudos to Peter Allen, at UC Santa Barbara, for the excellent illustration.

Tools to Challenge Cancer

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National Cancer Research Monthis an important reminder that cancer  is an insidious enemy. It’s always evolving. In order to shut cancer down and develop new therapies and cures, scientists have to attack it at its most fundamental level, and from as many angles as possible.

Sanford-Burnham has spent decades working against cancer. We were founded in 1976 as the La Jolla Cancer Research Foundation and have held a basic research cancer center designation from the National Cancer Institute for almost 30 years.

Our researchers are guided by the understanding that the most substantial breakthroughs come from studying the basic mechanisms of cells and the molecules that comprise them. The more strategies we adopt in the fight against cancer, the more opportunities we will have to develop new medicines. The following are examples of what Sanford-Burnham scientists study to continue that fight.

An Interview with Erkki Ruoslahti

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Dr. Erkki Ruoslahti, who recently published a paper in Science describing a novel way to improve cancer treatments, was interviewed on April 27 on KCSB radio. Speaking on the show  Intents & Purposes, Dr. Ruoslahti explained how his new technology, called iRGD,  helps cancer treatments penetrate tumors, potentially improving treatment for a wide variety of solid tumors.

“We can take any cancer drug and combine it with iRGD and it’s going to be more effective,” said Dr. Ruoslahti.

The complete podcast is available at the Intents & Purposes site.

Making Cancer Treatments Better

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One of the many challenges of creating effective cancer treatments is getting enough medicine to the tumor to kill it. Many treatments are administered intravenously and blood flow inside tumors is often limited at best. In addition, tumors generate a natural outward pressure, which forces anticancer drugs to “swim upstream.” As a result, treatments must be given in large doses to get more medicine to tumors.