Research
A glow that could put doctors in the know
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.
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.
Renewed SPORE grant helping ideas germinate
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.
Looking for tools to shut down leukemia for good
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.
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.
Breast cancer: You may never know until you ask the question
One of the coolest things about science is the endless number of questions that can be asked about something, and the resulting pursuit of answers.
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.
