Digital Swallowing Workstation (Photo courtesy Kay Elemetrics)

Swallowing seems automatic — something no one has to think about, like breathing or blinking. But for countless cancer patients, trying to take a gulp results in what’s called dysphagia — difficulties including gagging, coughing, dryness or pain.

The radiation therapy that knocks down cancers in the head and neck can often damage healthy tissue, too. And it takes more than 50 different muscles and nerves in the area working in perfect harmony to push food and fluid from the mouth to the stomach. That leaves a lot of room for error when it comes to swallowing.

City of Hope now is one of the few centers in California with a high-tech system that can help. Called the Digital Swallowing Workstation, the technology enables speech and language pathologists to watch what happens as a patient tries to swallow.

Tracing the process step by step, experts and patients can see which tissues aren’t working right during the swallowing process. That information leads to a sharing the right swallowing exercises or strategies along with educational resources that can make it easier for patients to enjoy eating again.

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Cancer isn’t one disease with one cure for everyone. It’s more complicated and depends on the patient’s genetic profile and the biology of the cancer. A recent study suggests that there may be as many as 10 types of breast cancer.

PET scanner

That helps to explain why some treatments don’t work against breast cancer, even when they seem like they should. A patient whose breast cancer is HER2-positive — that is, it expresses a lot of the protein called HER2 — is often treated with the drug Herceptin, which specifically targets the HER2 gene. But some HER2-positive patients don’t respond to Herceptin. There’s currently no easy way to tell in advance whether the drug will work for each HER2-positive patient.

So how can a woman avoid the side effects and cost of the drug if it’s unlikely to work — and choose a drug that might fight her cancer better?

Joanne Mortimer, M.D., director of City of Hope’s Women’s Cancers Program, is working on a diagnostic test to help identify HER2 patients who do and do not benefit from Herceptin treatment. Mortimer, together with her colleague James Bading, Ph.D., in the Department of Cancer Immunotherapeutics and Tumor Immunology, are using an imaging tool called positron emission tomography, or PET.

PET scanning uses small amounts of radiation to help doctors spot cancers in the body and see how they function. In the study, scientists use Herceptin that has been tagged with radiation. Doctors inject the Herceptin into the patient. If the patient’s tumors need HER2 protein to grow, the radiation on the tagged Herceptin will light up the tumors on the PET scan.

That lightbulb “aha!” moment may be a good indication that Herceptin treatment would benefit the patient. It might also identify other patients who possibly could benefit from Herceptin treatment even though their cancer doesn’t seem to be HER2-positive.

Most importantly, it also may identify those who wouldn’t benefit from Herceptin, so they could move on to other treatment options sooner.

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NanoKnife (Courtesy of AngioDynamics)

John Park, M.D., chief of the Division of Interventional Radiology in City of Hope’s Department of Diagnostic Radiology, and several of his colleagues have started using the new unit. The NanoKnife consists of several probes wired to an electric source. While a patient sleeps under anesthesia, doctors carefully insert the probes into the patient’s body so they surround the tumor. The physicians know just where to place the probes because they use CT scans, real-time ultrasound or other imaging methods to see the tumor’s location and size.

Once the probes rest in place around the tumor, the physicians send pulses of electricity into the NanoKnife. Electrons jump from probe to probe, jolting the tumor and punching holes in the cancerous cells in their path. The electricity flows for as little as 30 seconds. When it’s over, the tumor cells are damaged beyond repair. The body’s immune system then steps in to clean up dead cells.

The NanoKnife also affects nearby healthy tissues, but unlike surgery and procedures that use extreme heat or cold to kill tumor cells, the NanoKnife leaves the basic structures necessary for the body to rebuild the area with healthy cells. Best of all, patients report little or no pain following the procedure. “Patients want to go home as soon as they wake up,” Park said.

According to Park, the NanoKnife is most commonly used to treat tumors in soft tissues, such as in lung, prostate, pancreatic and liver cancers. Because clinical researchers are testing how well the NanoKnife works for specific cancers, the device currently is used only for patients with no other options or as part of a clinical trial.

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Cancer research can work that way. That’s why the National Cancer Institute (NCI) established a grant program to support Specialized Programs of Research Excellence, or SPOREs. These programs drive innovative studies involving both laboratory and clinical researchers targeting prevention, early detection, diagnosis and treatment of cancer. The goal: rapidly move basic scientific findings into clinical use to benefit patients.

The NCI recently renewed City of Hope’s Lymphoma SPORE grant, continuing groundbreaking research that first was recognized with a SPORE award in 2004.

City of Hope is pursuing four main projects through its Lymphoma SPORE.

T-cells engineered to fight non-Hodgkin lymphoma
T-cells are powerful immune system cells that fight disease. City of Hope scientists aim to re-engineer some of a lymphoma patient’s T cells so they target lymphoma cells and overcome the defenses that keep the lymphoma safe from the immune system. The treatment uses central memory T-cells, which potentially can provide a life-long immunity against lymphoma, preventing any relapse of the disease.

Avoiding treatment-related leukemia
Sometimes lymphoma treatment can put a patient at risk of developing leukemia later. Better understanding how a patient’s genetic profile may influence that cancer risk could help physicians tailor lymphoma treatment to minimize the chance of developing therapy-related leukemia.

Strategies for overcoming relapsed disease
Non-Hodgkin follicular lymphoma doesn’t give up easily; patients can have a high relapse rate and often must undergo many difficult treatments. Researchers are studying a protein that may help the immune system specifically target non-Hodgkin follicular lymphoma cells and protect patients against relapse.

Nanoparticles to infiltrate lymphoma cells
Minute tubes of carbon atoms called nanoparticles — each a tiny fraction of a hair’s width — can carry a therapeutic molecule to lymphoma cells to block cancer-boosting genes. Turning off those genes may kill the cancer, but making sure those nanoparticles can get into cancer cells and drop off the therapy is tricky. This project aims to make delivery more certain.

More than 60 SPOREs throughout the U.S. currently focus on different organs and disease sites in the body – among them brain, breast, kidney and lung. City of Hope remains one of only five centers in the country who have been awarded a Lymphoma SPORE grant.

These research efforts also receive support from the Tim Nesvig Lymphoma Fellowship and Research Fund.

WenYong Chen

City of Hope biologist WenYong Chen, Ph.D., is curious about its role in blood cancer. He’s targeted it as a potential survival mechanism for a form of leukemia. He and other scientists at City of Hope recently found that some chronic myelogenous leukemia cells use the gene as a life preserver, helping them stay alive during treatment.

The research is part of a scientific drive at City of Hope to end the threat of CML. Some projects look at how leukemia cells manipulate the tissue around them in the bone marrow; others focus on drugs that could potentially work together with existing treatments. Still others, like Chen’s, look at how leukemia resists today’s therapies.

Chen and his colleagues recently published a study in the journal Blood that showed that SIRT1 may be a reason that CML cells can grow resistant to the drug known as Gleevec or imatinib. Today, nine of every 10 leukemia patients taking the drug survive for at least five years, but patients can relapse.

Gleevec fights CML by blocking a mutant protein in the body that kicks off the blood cancer. By inactivating the protein, Gleevec pushes leukemia cells to wither and die — but not all of them. Why do some survive? The City of Hope team showed that leukemia cells produce a lot of SIRT1 — and SIRT1 shuts off a gene that suppresses leukemia.

Ultimately, treatment that interferes with SIRT1 could be a tool to fight this cancer in the future.

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A Zumba class gets people moving. (Photo by Patricia Duff Tucker)

City of Hope and its community partners are trying to spread the message about early cancer detection and colorectal health through an exercise craze that’s swept the country: Zumba.

Zumba’s Latin music booms and pulses with an infectious groove, getting dancers to jump and clap. Lines of Zumba fanatics routinely go out the door at exercise studios before classes start. That attraction recently drew participants to a series of Zumba classes in Duarte, Calif., — part of a health education effort by City of Hope’s Center of Community Alliance for Research & Education, or CCARE, and Set for Life, a community-based nonprofit focused on wellness. The groups plan to offer more classes in the future.

The class encourages health through fitness and provides potentially lifesaving health information for San Gabriel Valley residents age 50 or older. People attending an educational workshop about colorectal cancer can join the Zumba class for free.

The effort raises awareness about the importance of colorectal cancer prevention through healthy lifestyle changes and early detection. Just in time for Minority Cancer Awareness Month in April, the recent events aimed to reach Latino and African-American community members in particular. Latinos in the U.S. are less likely than people of any other ethnic group to get screened regularly for colorectal cancer. Too few African-Americans get screenings, too. Colorectal cancer tends to be more advanced when it’s diagnosed in these groups.

Recent sessions also introduced City of Hope experts to community members and featured a talk by City of Hope colorectal surgeon Julian Sanchez, M.D.

If you’re interested in Zumba, are age 50 or older or take care of someone 50 or older, and you live in the Los Angeles area, check City of Hope’s calendar or Set for Life, or call 626-644-7672 for any upcoming events.

When doctors and scientists saw that women in certain families were diagnosed with breast cancer far more often than they’d expect, they looked into whether cancer risk could be inherited. Those questions eventually led to the discovery of two genes in the 1990s — BRCA1 and BRCA2 — that changed how the medical world looks at cancer risk. Inherited mutations in these genes can dramatically increase the chances of developing breast and ovarian cancers.

City of Hope researchers continue to ask questions related to these gene mutations. In their studies of Latinas with BRCA-associated breast cancers, they noticed something unusual: Many of them had breast cancers that were progesterone receptor (PR) negative.

PR negativity means that the cancer doesn’t depend on the hormone progesterone to grow. That’s a challenge because some of the most successful modern therapies that block hormones aren’t as effective against these tumors.

Since about 1 in 4 Latinas with breast cancer have a BRCA mutation — a sizeable group — the scientists wanted to learn more.

City of Hope collaborated with the Clinical Cancer Genetics Community Research Network on the largest study of high-risk Latino families in the U.S, research presented recently at the annual meeting of the American Association for Cancer Research. They conducted complete BRCA testing and gathered detailed family trees.

Of the Latinas in the study diagnosed with a BRCA-associated breast cancer, about half were PR negative. That rate was much higher than in white non-Latinas with BRCA mutations. City of Hope researchers now are collecting data on white non-Latinas with breast cancer so they can better compare the two groups and understand the impact of PR negativity.

And as much as we admire Albert Einstein for his solitary work on understanding that whole “space-time” relationship, we also celebrate the group mind of scientists like Francis Crick, Rosalind A. Franklin and James D. Watson who, together, worked out the structure of DNA. Sometimes things are simply better in pairs — or trios.

Take highly active antiretroviral therapy, commonly called HAART, for one. Many physicians cite the introduction of HAART — basically a combination of three or more virus-fighting drugs — in the 1990s as a major turning point in HIV/AIDS treatment. Through HAART’s “drug cocktails,” what was once considered an immediate death sentence became a chronic condition that was manageable for most people infected with HIV.

Doctors came up with the combinations of drugs used in HAART only after each drug was approved and used individually. But today some researchers, including scientists at City of Hope, are looking at drug combinations for diseases like cancer much earlier, while the drugs are still in development.

They recently presented two lab studies of potential new combination cancer treatments for lymphoma and solid tumors at the annual meeting of the American Association for Cancer Research (AACR) in early April.

City of Hope’s Anna Scuto, Ph.D., assistant research professor of molecular medicine, presented the lymphoma study.

Scuto tested two investigational drugs that each push lymphoma cells to commit a sort of cellular suicide. When researchers put the drugs together, they worked much better against cancer than either did alone. That’s because the two drugs use different methods to drive cancer cells to kill themselves. Researchers think this combination approach may offer physicians a new strategy to fight lymphomas.

Scuto’s work has been sponsored in part by the Tim Nesvig Lymphoma Fellowship and Research Fund.

Wei Liang, Ph.D., a postdoctoral fellow in molecular medicine, presented the other study, which focused on immunotherapy.

Immunotherapies use the patient’s own immune system to battle cancer. The immune system gets rid of damaged cells, like cancer cells, and fights off bacteria and viruses. Cancer has a sneaky way of hiding and escaping from the immune system, though.

Liang focused on improving what’s called adoptive T-cell therapy. In this treatment, scientists tweak a patient’s own T cells to better recognize and fight cancer cells. But even re-engineered T -cells can have trouble overcoming cancer’s defenses. The investigational drug brivanib can reset these defenses. In Liang’s study, it boosted the number of T cells that could attack cancer — and made immunotherapy more effective.

Bhatia, who directs the Division of Hematopoietic Stem Cell and Leukemia Research, and his colleagues published their study in the April 16 issue of the journal Cancer Cell.

Cancer cells can change the area around them to make conditions better for cancer to grow. In the case of a pancreatic tumor, for example, cancer cells can hide the tumor away from the immune system or encourage the pancreas to grow new blood vessels to feed the tumor. Cancer cells can change the immediate area surrounding the tumor — what scientists call the microenvironment — to help the tumor out.

Leukemia affects the bone marrow microenvironment in a similar way. It turns the area into a space that’s friendlier to leukemia cells. Even if powerful modern medicines successfully kill mature leukemia cells, leukemia stem cells can hide away in the bone marrow, manipulate it and emerge to cause CML again if patients stop taking the drugs.

Researchers think the information may lead to new strategies to counter CML. If scientists can better understand how the disease makes these long-term changes to the microenvironment, they may be able to find better treatments that can wipe out all leukemia cells and prevent them from returning. His team is continuing its investigations.

From left, David Horne, Bubba Watson and John Williams at the Northern Trust Open

Horne loves golf. He grew up playing the storied golf courses at Pebble Beach, Calif., and caddied at the Bing Crosby Pro-Am tournament in his younger days. But there’s more to it than that. Horne is chair of the Department of Molecular Medicine at City of Hope, and Watson is helping to make his cancer-fighting ideas a reality.

An ongoing partnership between Watson and the golf apparel company Travis Mathew will send critical dollars to City of Hope to support research by Horne and John C. Williams, Ph.D., associate professor of molecular medicine. Horne and Williams are creating a new way to deliver therapies straight to cancer cells in the body, reducing damage to healthy cells. That could make medicines more effective and cause fewer side effects.

They’re studying and designing meditopes: tiny, customizable cargo that can be loaded onto monoclonal antibodies made in a lab. Monoclonal antibodies can be injected into the body and grab onto to specific spots on cancer cells, delivering their cargo. The scientists aim to get a potential therapy to clinical trials within five years.

The two researchers talked with Watson at the Northern Trust Open in Los Angeles in February, an inspiring experience they won’t soon forget. Watson’s father died of throat cancer in 2010, so he understands the need for better treatments. He’s also committed to supporting important causes.

“I’ve become a big fan of Bubba’s since meeting him,” Williams says. “I watched him the last day of the Northern Trust Open and at Doral [at the World Golf Championships] on TV.” And despite having to travel during the Masters, he followed Watson’s progress on his cell phone.

Horne was equally thrilled. “I was so excited to see Bubba win the Masters. I’ve never rooted harder for anyone else,” he says. “It was such an exciting finish. He is an amazing golfer and human being.”

The scientists are especially grateful to Travis Mathew and its founding investor, John Kruger. Without their private support, it would be tough to move the research forward. Scientists with high-risk, high-reward projects often struggle to get funding from big pharmaceutical companies and the National Institutes of Health, especially during financial belt-tightening. “We absolutely need this kind of support to develop this novel technology to get it to the clinic,” Williams says.