Imagine you’re in the park with a packed basket full of delicious food, especially that 3-tiered red velvet cake serenading you like a siren. It might seem hard to believe, but for purposes of this analogy, it’s actually a brain tumor. And somehow it’s wedged in between the fruit salad and the egg salad sandwiches. You can’t get to it without damaging the important stuff around it.
Hungry? Let’s get to the point of this picnic metaphor.
City of Hope recently was granted a $5.2 million research award by the California Institute for Regenerative Medicine (CIRM) to support development of a therapy to attack brain tumors. This T cell-based immunotherapy would redirect a patient’s immune system to fight glioma stem cells.
Glioma is a type of brain tumor that can be difficult to treat and often returns after therapy. Currently, less than 20 percent of patients with malignant gliomas are living five years after their diagnosis. This poor prognosis is mostly because of cancer stem cells. These malignant cells are similar to normal stem cells in that they can reproduce indefinitely. They’re also highly resistant to chemotherapy and radiation therapy, so they can stick around and start new tumors after a patient undergoes treatment.
CIRM’s grant supports a potential new therapy that engineers T cells to go after several proteins linked to glioma cells. Phase I trials already are under way at City of Hope for T-cell therapies using other proteins.
Now back to that picnic. Think of engineered T cells as an army of ants. They’re drawn specifically to red velvet cake, leaving the rest of the basket alone. The ants tear apart the cake and haul it away.
In another picnic basket, ants might be targeted to attack a hoagie — a pancreatic tumor. Or maybe they go for the caprese salad — in this case, breast cancer. Different armies of T cells could swarm to specific targets as needed.
In the end, the cake, sandwich or salad might be gone, but the picnic would go on.
The last few days have seen some pretty passionate debate around the country about prostate cancer screening. Should men routinely get PSA tests even though most of the men with elevated PSA levels actually have no cancer?
A federal panel suggested that these tests for PSA (prostate-specific antigen) do more harm than good because suspicious results put many men through follow-up testing that proves unnecessary. When screening shows a man has high PSA levels, doctors take a prostate biopsy, or tissue sample. If the sample doesn’t seem to have cancer cells, but PSA levels stay high over time, doctors keep taking these costly and potentially painful biopsies to make sure there’s really no cancer.
But many doctors say the recommendation does a disservice because the tests can find prostate cancer when it’s most treatable.
Now technology under development could potentially provide a faster, more efficient answer about whether a man has cancer, taking some of the sting out of the process.
City of Hope researchers shared their latest results this morning at the American Urological Association annual meeting in Atlanta. They showed that a tiny device they developed can tell the difference between prostate cancer and benign prostatic hyperplasia. This is a common, non-cancerous condition that can cause high levels of PSA, or prostate-specific antigen, just like prostate cancer does.
The nanodevice is a molecule created to glow under a special light. They’ve engineered it so that it’s drawn to enzymes active in cancer. When they exposed samples of prostate stromal tissue (supportive tissue) to their molecules, the samples that had prostate cancer glowed more intensely than tissue with benign prostatic hyperplasia. They hope that doctors can eventually use the technology to diagnose prostate cancer more accurately — the first time.
People over age 65 account for three out of every five cancer cases, and as the media regularly remind us, the Baby Boomer generation is aging into seniors. This Boomer bubble is bringing a medical research problem to light: too few seniors take part in clinical trials of new cancer therapies.
“There is an overwhelming amount of evidence showing that older adults react differently to cancer drugs,” says Arti Hurria, M.D., director of City of Hope’s Cancer and Aging Research Program. As people grow older, the liver and kidneys don’t work as well, so drugs tend to stay in the body longer.
Because too few seniors are participating in studies of new drugs, though, doctors have less data about how well drugs work — and about their potential side effects — in this age group. And the more data that’s available to physicians, the better their decisions and recommendations for patients.
Kevin Scher, M.D., a second-year hematology fellow at City of Hope, co-wrote a paper with Hurria on this issue for the May issue of the Journal of Clinical Oncology. They’re urging that more seniors be included in clinical trials.
The researchers noted some surprising statistics:
- Even though 60 percent of people with cancer in the U.S. are 65 or older, they make up only a third of the people in clinical trials.
- Many studies have so few participants older than 75 that they don’t even report them — even though this age group makes up about 30 percent of cancer patients.
They’re calling for a mandate to include more older adults in drug trials. The strategy has worked before with drugs used by children and adolescents. The Pediatric Research Equity Act of 2003 gave the Food and Drug Administration the authority to mandate pediatric trials for drugs used primarily in this age group. Since the legislation’s passage, information about the effects of medications in pediatric patients has grown significantly.
Warren Buffett’s recent revelation about his prostate cancer diagnosis re-opened the debate over age and prostate cancer screening and treatment. At 81, Buffett falls outside of the commonly used guidelines that men over 75 don’t need to be screened for prostate cancer.
The United States Preventive Services Task Force made this recommendation in 2008, noting that most men over age 75 who develop prostate cancer die from other causes. Since prostate cancer in older men tends to develop slowly, experts say, these men do not need treatment that can cause incontinence and other side effects.
Interestingly, the task force announced its prostate cancer screening recommendations a year before it unveiled its recommendation that breast cancer screening should begin at 50 instead of the current 40 years of age. There was sustained public outrage over the breast cancer screening recommendations, but little hubbub over the guidelines on prostate cancer.
We should remember that guidelines are created to help the majority of people, and individuals can fall on either side of that bell curve — developing prostate cancer earlier or later in life than the typical patient. Men are encouraged to talk with their doctor about their personal health concerns and whether screening is right for them.
Timothy Wilson, M.D., Pauline and Martin Collins Family Chair in Urology and chief of the Division of Urology & Urologic Oncology, shares his thoughts in this video about the value of prostate cancer screening.
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.
Physicians know it. Researchers know it. Breast cancer patients learn it quickly after diagnosis.
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.
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.
City of Hope radiologists are using the NanoKnife, a medical tool that destroys tissue using electricity, to zap stubborn tumors that do not respond to chemotherapy or radiation and that lie in locations that are difficult to reach with traditional surgery.
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.
One idea can change the world — especially when people from diverse perspectives work together to bring that idea to fruition.
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.
Some people call it the longevity gene. It’s known as sirtuin 1, or SIRT1, and depending on who you talk to, it can either extend lifespan or limit it. And sometimes it can fight cancer, but at times it can promote the disease, too.
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.
It can take a little creativity and education to get some people to go through a colonoscopy for the first time, but it’s worth it: When colorectal cancer is caught early, doctors can treat it fairly easily and survival rates are high.
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.