TAG: "Cancer"

Study to examine risks, benefits of chemotherapy for early-stage breast cancer


Research aims to better inform physicians, patients about optimal treatment strategies.

Joy Melnikow, UC Davis

Treatment for early stage breast cancer is highly effective, and for many women considering treatment choices, chemotherapy may add little to an already high long-term survival rate. Joy Melnikow, professor in the Department of Family and Community Medicine and director of the Center for Healthcare Policy and Research at UC Davis, is working to define the potential long-term harms of chemotherapy for these patients, so they can be weighed against the potential benefits.

Her study, funded by the National Cancer Institute (NCI), aims to better inform physicians and their patients about optimal treatment strategies. She also hopes to identify gaps in the evidence to date that require additional research.

“It‘s important to know when you can say the evidence is strong and when it is not,” she said.

Melnikow said treatment regimens vary for early-stage invasive breast cancer. In many cases, women opt for a lumpectomy (surgical removal of the tumor) with radiation, or a mastectomy (removal of one or both breasts) with the addition of hormonal therapy and/or chemotherapy and sometimes trastuzumab (Herceptin), a monoclonal antibody treatment.

“The survival from treatment with or without adjunctive chemotherapy is extremely good for many women with early-stage disease, so the incremental benefit of chemotherapy may be small,” she said. “The question is how to balance the benefits with the potential long-term harms of chemotherapy.”

Melnikow and her colleagues are conducting a series of systematic reviews of the published literature to extract and synthesize what is known about a range of potential long-term harms of chemotherapy for early-stage breast cancer. The harms may include congestive heart failure, ovarian failure (for premenopausal women), peripheral neuropathy, cognitive impairment, and secondary cancers from the effects of chemotherapy on the DNA of non-breast cancer cells.

In addition to identifying and reviewing all available published evidence on the topic, Melnikow also is working with her colleagues to mine previously unpublished data from the NCIB-30 trial of chemotherapy regimens for early-stage breast cancer.

“We hope our work will provide new information to help women and their doctors make decisions about breast cancer chemotherapy,” she said. “We also expect to define critical gaps in the evidence that can inform future research in this area.”

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Stem cell therapy coming of age


With first clinical trials, UC San Diego pushes stem cell therapies into new era.

Photos by Erik Jepsen, UC San Diego

In 2004, the therapeutic potential of stem cells persuaded more than 7 million Californians to approve Proposition 71, which allocated a whopping $3 billion for research and development of stem cell-based drugs and therapies that might someday address a medical dictionary’s worth of diseases and conditions.

Now, stem cell research is being put to the test in full force as years of cellular and animal studies make the leap to human clinical trials—a requisite step before any new drug or therapy is approved for market. Nowhere is this progress more visible than at UC San Diego, which in recent weeks has launched the three first stem-cell-based clinical trials in patients to pursue potential treatments for spinal cord injury, Type 1 diabetes and chronic lymphocytic leukemia.

And last week, the California Institute for Regenerative Medicine (CIRM), the state stem cell agency established by Prop.71, named the Sanford Stem Cell Clinical Center at UC San Diego Health System one of three “alpha clinics,” a highly sought-after designation that comes with an $8 million grant to further speed stem cell clinical development. The other two alpha clinic sites are City of Hope hospital near Los Angeles and UCLA, which is partnering with UC Irvine.

“A UC San Diego alpha clinic will provide a vital infrastructure for establishing a comprehensive regenerative medicine clinical hub that can support the unusual complexity of first-in-human stem cell-related clinical trials,” said Dr. Catriona Jamieson, deputy director of the Sanford Stem Cell Clinical Center, director of the UC San Diego Moores Cancer Center stem cell program and the alpha clinic grant’s principal investigator.

“The designation is essential in much the same manner that comprehensive cancer center status is an assurance of scientific rigor and clinical quality. It will attract patients, funding agencies and study sponsors to participate in, support and accelerate novel stem cell clinical trials and ancillary studies for a range of arduous diseases.”

Lawrence Goldstein, director of the UC San Diego Stem Cell Program and Sanford Center

Such work is well underway. Last week, doctors at UC San Diego and Veterans Affairs San Diego Healthcare System, in collaboration with the San Diego-based biotechnology firm ViaCyte, Inc., treated the first patient in an unprecedented phase one-two trial of a stem-cell-derived therapy for patients with Type 1 diabetes. The trial involves implanting specially encapsulated embryonic stem-cell-derived cells under the skin where it’s hoped they will mature into pancreatic beta and other cells able to produce a continuous supply of needed insulin and other substances.

Last month, a 26-year-old woman paralyzed in a car accident a year ago successfully underwent the first experimental procedure to test whether neural stem cells injected at the site of a spinal cord injury is safe and could be an effective treatment. It is hoped that the procedure – the first of four in the phase one trial sponsored by the Sanford Center and Maryland-based Neuralstem Inc. – will ultimately lead to a treatment in which transplanted neural stem cells will develop into new neurons that bridge the gap created by an injury, replace severed or lost nerve connections and restore at least some motor and sensory function.

Also last month, researchers at UC San Diego Moores Cancer Center and the Sanford Center treated the first participant in a novel phase one trial to assess the safety of a monoclonal antibody treatment that targets cancer stem cells in patients with chronic lymphocytic leukemia, the most common form of blood cancer.

“What we are seeing after years of work is the rubber hitting the road,” said Lawrence Goldstein, director of the UC San Diego Stem Cell Program and Sanford Center. “These are three very ambitious and innovative trials. Each followed a different development path; each addresses a very different disease or condition. It speaks to the maturation of stem cell science that we’ve gotten to the point of testing these very real medical applications in people.”

Goldstein noted that the number of patients involved in these first trials is small. Their focus is upon treatment with low doses to assess safety, but also with hope of patient benefit. As these trials progress – and additional trials are launched – Goldstein predicts greater numbers of patients will be enrolled at UC San Diego, the Sanford Center and elsewhere.

Achieving alpha clinic status should help, he said. One element of the new grant is expanded public outreach to raise awareness and understanding of stem cell science, in part to combat what Goldstein calls “stem cell tourism” and the marketing of unproven, unregulated and potentially dangerous therapies.

“Clinical trials are the fastest and safest way to develop therapies that are truly safe and that actually work. You want to prove that a new therapy will work for more than just a single, random patient. These alpha clinic awards not only provide valuable support that will help accelerate experimental stem cell therapies into clinical trials, they also bring with them a ‘stamp of approval’ that our center meets important standards set by peers for testing of stem cell therapy trials.”

The alpha grant reflects CIRM’s continued support for UC San Diego’s stem cell research and development efforts. Since 2004, CIRM has approved 74 awards totaling more than $147 million to UC San Diego stem cell scientists and programs. The three clinical trials launched are just the first of many to come, said alpha clinic principal investigator Jamieson. Other trials for heart failure, amyotrophic lateral sclerosis (Lou Gehrig’s disease) and blindness are in the planning stages.

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Two UC centers named stem cell ‘alpha clinics’

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‘Treasure in saliva’ may reveal deadly diseases early enough to treat them


UCLA research holds promise for diagnosing Type 2 diabetes, gastric cancer, other diseases.

Xinshu (Grace) Xiao and David Wong, UCLA (Photo by Reed Hutchinson, UCLA)

UCLA research could lead to a simple saliva test capable of diagnosing — at an early stage — diabetes and cancer, and perhaps neurological disorders and autoimmune diseases.

The study, the most comprehensive analysis ever conducted of RNA molecules in human saliva, reveals that saliva contains many of the same disease-revealing molecules that are contained in blood. It was published online today (Oct. 29) by the peer-reviewed journal Clinical Chemistry and will be published in the journal’s January 2015 special print issue, “Molecular Diagnostics: A Revolution in Progress.”

“If we can define the boundaries of molecular targets in saliva, then we can ask what the constituents in saliva are that can mark someone who has pre-diabetes or the early stages of oral cancer or pancreatic cancer — and we can utilize this knowledge for personalized medicine,” said Dr. David Wong, a senior author of the research and UCLA’s Felix and Mildred Yip Endowed Professor in Dentistry.

Wong said the test also holds promise for diagnosing Type 2 diabetes, gastric cancer and other diseases. “If you don’t look in saliva, you may miss important indicators of disease,” Wong said. “There seems to be treasure in saliva, which will surprise people.”

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Arsenic in drinking water linked to 50% drop in breast cancer deaths


‘What we found was astonishing.’

One typically does not hear talk of the health benefits of arsenic, but a new study by researchers from UC Berkeley and the Pontifical Catholic University of Chile has linked arsenic to a 50 percent drop in breast cancer deaths.

The study, published this month in the journal EBioMedicine, presents results of breast cancer mortality data from a region in Chile where residents were inadvertently exposed to high levels of arsenic, a naturally occurring element found in many minerals. Instead of an increase in mortality, as with many other cancer sites, the study found that breast cancer deaths were cut in half during the period that coincided with high arsenic exposure. The effect was more pronounced among women under age 60, with mortality in these women reduced by 70 percent.

“What we found was astonishing,” said study lead author Dr. Allan Smith, UC Berkeley professor of epidemiology and director of the Arsenic Health Effects Research Program. “We’ve been studying the long-term effects of arsenic in this population for many years, focusing on increased disease and mortality attributed to the historical exposure to arsenic in this population.”

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Biopsy quality directly linked to survival in patients with bladder cancer


For about half of those with the disease, doctors don’t get sufficient sample to correctly stage the cancer.

Karim Chamie, UCLA

UCLA researchers have shown for the first time that the quality of diagnostic staging when performing biopsies on patients with bladder cancer is directly linked with survival, meaning those who don’t get optimal biopsies are more likely to die from their disease.

The two-year study found that about half of bladder cancer patients who were biopsied had insufficient material — meaning that no bladder wall muscle was retrieved — to accurately stage the cancer. Additionally, the UCLA research team found that a less-than-optimal biopsies and incorrect tumor staging were associated with a significant increase in deaths from bladder cancer, said the study’s first author, Dr. Karim Chamie, an assistant professor of urology and surgical director of the bladder cancer program at UCLA.

“These findings are very important because while patients know about the stage of their cancer, they rarely question the quality of the biopsy,” said Chamie, who also is a researcher at UCLA’s Jonsson Comprehensive Cancer Center. “We hope these findings will help empower patients to ask about the quality of their biopsy and, if it is suboptimal, then urge their doctors to repeat the biopsy prior to deciding on what type of treatment to prescribe.”

The findings were published Oct. 22 in the early online edition of the peer-reviewed journal Cancer. The study was conducted at UCLA and the Cancer Surveillance Program at USC.

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National Cancer Institute funds study on Western diet, role in GI cancer


UC Davis researchers also will study if friendly bacteria can prevent it.

The National Cancer Institute (NCI) has awarded a $2.7 million grant to UC Davis researchers to investigate how the so-called Western diet, which is high in fat and sugar, increases the risk of developing liver and gastrointestinal (GI) cancers. In addition, the researchers will study whether bifidobacteria, a common family of bacteria in the human gut, can be enriched to prevent cancer.

“We know that people who are obese or diabetic have increased risk for GI cancer,” said Yu-Jui Yvonne Wan, one of three principal investigators and vice chair for research in the Department of Pathology and Laboratory Medicine. “But we need to have a better understanding of how these conditions lead to cancer and how to prevent it.”

Other principal investigators on the study are professors Carolyn Slupsky and David Mills, both in the Department of Food Science & Technology and members of the Foods for Health Institute.

The study’s first goal will be to understand how the Western diet affects metabolism, bile acid and friendly bacteria (microbiota). While researchers already have learned that diets high in fat and sugar generate toxic bile acid, which causes inflammation and damages DNA, the mechanisms of this process are poorly understood.

Perhaps most importantly, the researchers also will investigate whether specific bifidobacteria species can mitigate the Western diet’s negative effects. The team will test whether a combination of complex milk sugars and bifidobacteria can reduce inflammation and short-circuit the mechanisms that generate cancer.

“When we talk about gastrointestinal health, we have to think about microbiota,” said Wan. “We believe that enriching the gut with anti-inflammatory bifidobacteria can protect against GI cancer.”

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Training next generation of cancer scientists


National Cancer Institute training grant has supported UC San Diego scholars since 1984.

Key coordinators and newly appointed trainees of UC San Diego's Cancer Training Program. (From left) Annie Chou, Laura Castrejon, Daniel Donoghue, David Cheresh, Juliati Rahajeng, Amy Haseley Thorne and Jasmine Wang.

UC San Diego received a $2.5 million Institutional Ruth L. Kirschstein National Research Service Award from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), to support four predoctoral and six postdoctoral scholars in the campus’s cancer training program. First awarded in 1984, the grant is the single longest-running NCI training grant at UC San Diego. The 2014 grant renewal will provide funding through 2019, when it will have completed 34 years of training for cancer investigators.

The cancer training grant, administered through the Department of Chemistry and Biochemistry in the UC San Diego Division of Physical Sciences, focuses on the study of growth regulation and oncogenesis, with the goal of understanding cancer from a cell biological and biochemical perspective. To date, the program has supported the advanced training of more than 200 predoctoral and 100 postdoctoral trainees.

“Past trainees have made many key discoveries that have paved the way for the ongoing revolution in personalized cancer therapies,” said Daniel Donoghue, Ph.D., professor of chemistry and biochemistry and training program director. Donoghue also serves as provost of UC San Diego’s Sixth College. “We are delighted that NCI has recognized the importance of our work by continuing to fund our trainees for the next five years. We can expect more key discoveries through this program.”

Among the researchers who have completed the training program are Beth Baber, who established a pediatric cancer institute — The Nicholas Conor Institute — in 2009 and Kun Ping Lu, a current Harvard University faculty member who identified a new cancer target that is now being developed therapeutically. Daniel Knighton, another past trainee, collaborated with his mentor in the cancer training program to solve the first crystal structure of a protein kinase in a large family of cancer targets.

“All of us at some point in our lives will be touched by cancer, sadly the number one cause of mortality in San Diego,” said Scott M. Lippman, M.D., director of UC San Diego Moores Cancer Center. “We are in the beginning phases of a transformation in the detection and treatment of cancer, the rate of which will depend on our ability to train the next generation of cancer scientists who will lead the innovative efforts, scientific discoveries and technology development that could change how we treat cancer tomorrow.”

The training program is comprised of 32 participating faculty members, including seven faculty who are members of the National Academy of Sciences, one Nobel laureate, four Fellows of the American Association for Cancer Research (AACR), one past president of the AACR and one Lasker Award recipient.

All participating faculty are members of UC San Diego Moores Cancer Center, which acts as an umbrella for the various UC San Diego units including the department of chemistry and biochemistry, the Division of Biological Sciences, the School of Medicine, the Salk Institute for Biological Studies, as well as the Ludwig Institute for Cancer Research.

“This generous award will promote vital research productivity and allow synergistic scientific interactions between brilliant minds working in different organizations towards advancing our understanding of basic cell biological events that cause cancer,” said David Cheresh, Ph.D., associate director for innovation and industry alliances at Moores Cancer Center, distinguished professor of pathology, and co-chair of the training program. “Together we can identify drugs and innovative strategies for new cancer therapies.”

Key supporters of the cancer training program include Lippman; Suresh Subramani, executive vice chancellor of academic affairs at UC San Diego; David Brenner, vice chancellor of health sciences at UC San Diego; Web Cavenee, director of the Ludwig Institute of Cancer Research, San Diego Branch; and 32 participating faculty mentors.

More information about the cancer training program can be found online at cancertraining.ucsd.edu.

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Radiation exposure is linked to aggressive thyroid cancers


International team studied children exposed after Chernobyl.

For the first time, researchers have found that exposure to radioactive iodine is associated with more aggressive forms of thyroid cancer, according to a careful study of nearly 12,000 people in Belarus who were exposed when they were children or adolescents to fallout from the 1986 Chernobyl nuclear power plant accident.

Researchers examined thyroid cancers diagnosed up to two decades after the Chernobyl accident and found that higher thyroid radiation doses estimated from measurements taken shortly after the accident were associated with more aggressive tumor features.

“Our group has previously shown that exposures to radioactive iodine significantly increase the risk of thyroid cancer in a dose-dependent manner. The new study shows that radiation exposures are also associated with distinct clinical features that are more aggressive,” said the paper’s first author, Lydia Zablotska, M.D., Ph.D., associate professor in the Department of Epidemiology and Biostatistics at UC San Francisco. The paper will be published online Tuesday, Oct. 28, in the journal Cancer.

Zablotska said the findings have implications for those exposed to radioactive iodine fallout from the 2011 nuclear reactor incidents in Fukushima, Japan, after the reactors were damaged by an earthquake-induced tsunami.

“Those exposed as children or adolescents to the fallout are at highest risk and should probably be screened for thyroid cancer regularly, because these cancers are aggressive, and they can spread really fast,” Zablotska said. “Clinicians should be aware of the aggressiveness of radiation-associated tumors and closely monitor those at high risk.”

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Anti-cancer drug found effective vs. common stem cell transplant complication


Trial shows that bortezomib provides better outcomes than existing treatments.

Researchers at UC Davis have found that the drug bortezomib effectively treats chronic graft-versus-host disease (GVHD), a common and debilitating side effect from allogeneic hematopoietic stem cell transplants. The trial showed that bortezomib provides better outcomes than existing treatments and does not impair the immune response against residual cancer cells, or the graft-versus-tumor effect (GVT).

“Bortezomib helped a group of patients who desperately needed a treatment, having failed multiple different therapies,” said UC Davis hematologist and associate professor Mehrdad Abedi, lead author on the paper. “The drug fights chronic graft-versus host disease, and unlike other GVHD therapies such as steroid, cyclosporine or mycophenolate, it treats chronic GVHD without dampening the graft-versus-tumor effect, which can be critically important to help patients avoid relapse. In fact, because bortezomib is an anti-cancer drug, it potentially attacks cancer cells in its own right.”

The trial results were published in October in the journal Blood.

Chronic GVHD strikes patients who have received stem cell transplants from donors, commonly called allogeneic transplants. Although the transplants are close matches, they are not identical, and donor cells can attack the recipient, damaging skin, lungs, kidneys and other organs, which can be life threatening.

Developed by Millennium Pharmaceuticals, bortezomib has been used to treat multiple myeloma, leukemia and lymphoma. The drug also has been studied against acute GVHD, making it a promising option against the chronic version of the disease.

The researchers first studied bortezomib in mice, in which the drug delivered excellent results.

The investigation, in collaboration with William Murphy, professor and acting chair of the Department of Dermatology and a co-senior author, found that bortezomib suppresses the donor immune cells that cause GVHD.

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Stem cell science takes bold step at UC San Diego


Three first-in-human clinical trials are underway.

A 26-year-old woman paralyzed after a motor vehicle accident a year ago has successfully undergone a first-in-human experimental procedure to test whether neural stem cells injected at the site of a spinal cord injury is safe and could be an effective treatment.

The procedure, conducted on Sept. 30 under the auspices of the Sanford Stem Cell Clinical Center at UC San Diego Health System and in collaboration with Neuralstem Inc., a Maryland-based biotechnology firm, is the first of four in the phase one clinical trial. Post safety testing, it’s hoped that the transplanted neural stem cells will develop into new neurons that bridge the gap created by the injury, replace severed or lost nerve connections and restore at least some motor and sensory function.

The patient, whose identity remains confidential for privacy reasons, has been discharged and is recovering without complication or adverse effects at home, said Joseph Ciacci, M.D., principal investigator and neurosurgeon at UC San Diego Health System.

The spinal cord injury trial is one of three recent groundbreaking stem cell efforts at UC San Diego, supported by the Sanford Stem Cell Clinical Center, to make the significant leap from laboratory to first-in-human clinical trials.

Last month, researchers at UC San Diego Moores Cancer Center and the Sanford Stem Cell Clinical Center launched a novel phase one trial to assess the safety of a monoclonal antibody treatment that targets cancer stem cells in patients with chronic lymphocytic leukemia, the most common form of blood cancer.

And later this month, the first patient is scheduled to receive an unprecedented stem cell-based therapy designed to treat type 1diabetes in another phase one clinical trial at UC San Diego.

“What we are seeing after years of work is the rubber hitting the road,” said Lawrence Goldstein, Ph.D., director of the UC San Diego Stem Cell program and Sanford Stem Cell Clinical Center at UC San Diego Health System. “These are three very ambitious and innovative trials. Each followed a different development path; each addresses a very different disease or condition. It speaks to the maturation of stem cell science that we’ve gotten to the point of testing these very real medical applications in people.”

To be sure, Goldstein said, the number of patients involved in these first trials is small. The initial focus is upon treatment with low doses to assess safety, but also with hope of patient benefit. As these trials progress – and additional trials are launched – Goldstein predicts greater numbers of patients will be enrolled at UC San Diego and the Sanford Stem Cell Clinical Center and elsewhere.

“Clinical trials are the safest way to pursue potential therapies. You want to prove that a new therapy will work for more than just a single, random patient.”

While stem cell-based trials are beginning to emerge around the country, Goldstein noted that San Diego continues to assert itself as a stem cell research hub and a leading force for translating basic discoveries into medical applications, now and in the future.

“These innovative trials are the result of some truly rare features you find at UC San Diego and in the region,” he said. “There is a unique sense of collaboration and communication here among scientists in academia, clinical medicine and the biotechnology industry. An enterprise like the Sanford Center can promote and accelerate the very complex processes of research, development and testing so that the right people make the right connections and the right ideas and trials get fast-tracked, but in a way that ensures fundamentally the safety of patients while striving for benefit.”

More about the three trials:

Neural stem cell transplants and spinal cord injuries
The Neuralstem phase one clinical trial, conducted over five years with four patients, is designed to assess the safety and efficacy of an approach that might, it is hoped, someday be a treatment for paralyzing spinal cord injuries.

In preclinical studies, Ciacci and Martin Marsala, M.D., a professor in the Department of Anesthesiology at UC San Diego School of Medicine and the Sanford Consortium for Regenerative Medicine, and colleagues grafted human neural stem cells into rats with spinal cord injuries. The introduced cells showed extensive growth and connected to remaining nerve cells near the injury site, resulting in significantly improved motor function with minimal side effects in animal models.

The goal now is to determine whether similar effects occur in human patients. The researchers will also test for possible therapeutic benefits, such as reduced paralysis and improvements in motor and sensory function, bowel and bladder function and pain levels.

VC-01 and Type 1 diabetes
In collaboration with ViaCyte Inc., a San Diego-based biotechnology firm specializing in regenerative medicine, UC San Diego researchers led by principal investigator Robert Henry, M.D., professor of medicine in the Division of Endocrinology and Metabolism at UC San Diego and chief of the Section of Endocrinology, Metabolism & Diabetes at the Veterans Affairs San Diego Healthcare System, have launched the first-ever phase one-two clinical trial of a stem cell-derived therapy for patients with Type 1 diabetes. The first procedure is planned for later this month, with a second tentatively scheduled in mid-November.

Type 1 diabetes mellitus is a life-threatening chronic condition in which the pancreas produces little or no insulin, a hormone needed to allow glucose to enter cells to produce energy. It is typically diagnosed during childhood or adolescence, but can also strike adults. Though far less common than Type 2 diabetes, which occurs when the body becomes resistant to insulin, Type 1 may affect up to 3 million Americans with emotionally and financially devastating consequences. Standard treatment involves daily injections of insulin and rigorous management of diet and lifestyle. Currently, there is no cure.

The two-year trial will involve approximately 40 study participants at four to six testing sites, with San Diego being first. The trial will assess the safety, tolerability and efficacy of varying doses of VC-01, which involves implanting specially encapsulated embryonic stem cell-derived cells under the skin of patients where it’s hoped they will safely mature into pancreatic beta and other cells able to produce a continuous supply of needed insulin and other substances.

Development and testing of VC-01 is funded, in part, by the California Institute for Regenerative Medicine (CIRM), Sanford Stem Cell Clinical Center and JDRF, formerly known as the Juvenile Diabetes Research Foundation. Clinical testing and coordination is provided by UC San Diego Clinical and Translational Research Institute.

Cirmtuzumab and leukemia
Researchers at UC San Diego Moores Cancer Center and the Sanford Stem Cell Clinical Center have launched a phase one human clinical trial to assess the safety and efficacy of a new monoclonal antibody for patients with chronic lymphocytic leukemia (CLL), the most common form of blood cancer in adults.

The drug, called cirmtuzumab, targets a molecule called ROR1 that normally is used only by embryonic cells during early development, but which is abnormally exploited by cancer cells to promote tumor growth and spread, otherwise known as metastasis. Metastasis is responsible for 90 percent of all cancer-related deaths.

Because ROR1 is not used by normal adult cells, scientists believe it is a unique marker of cancer cells in general and cancer stem cells in particular. ROR1 appears to drive tumor growth and disease spread and scientists think that presents an excellent novel target for anti-cancer therapy.

Cirmtuzumab was developed at Moores Cancer Center in the laboratory of Thomas Kipps, M.D., Ph.D., who led this effort as one of six projects initially funded through CIRM’s HALT leukemia grant to co-principal investigators Dennis Carson, M.D., and Catriona Jamieson, M.D., Ph.D.  The drug’s name acknowledges CIRM’s continued support in a “Disease Team III” award, which provides some of the resources needed for a clinical trial. The Leukemia and Lymphoma Society has also provided additional support.

The trial will involve patients with relapsed or refractory CLL receiving an intravenous infusion every 14 days at Moores Cancer Center, followed by regular monitoring and clinic visits to assess efficacy and identify and manage any adverse effects. Initial treatment is planned for two months.

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New target ID’d for personalized brain cancer treatment


UC San Diego finding focuses on a fusion protein.

Clark Chen, UC San Diego

Researchers at the UC San Diego School of Medicine have identified a new fusion protein found in approximately 15 percent of secondary glioblastomas or brain tumors. The finding offers new insights into the cause of this cancer and provides a therapeutic target for personalized oncologic care. The findings were published this month in the online edition of Genome Research.

Glioblastoma is the most common and deadliest form of brain cancer. The majority of these tumors – known as primary glioblastomas – occur in the elderly without evidence of a less malignant precursor. Secondary glioblastomas occur mostly in younger patients and progress from low-grade, less aggressive precursor tumors to glioblastoma, the most aggressive form of the disease.

“While genomic profiling is yielding improved understanding of primary glioblastoma, our understanding of secondary glioblastoma remains rudimentary,” said Clark Chen, M.D., Ph.D., vice chairman of research and academic development, Division of Neurosurgery, UC San Diego School of Medicine and a principal investigator of the study. “In this study, we used a technology called RNA-Seq to study the RNA sequences derived from 272 clinical tumor specimens from patients afflicted with secondary glioblastoma or precursor forms of this tumor.”

The study revealed that the RNA sequences of brain cancers become progressively more abnormal as the tumor become more malignant. Specifically, the frequency of aberrant RNAs fusing gene sequences not normally found next to one another increased with tumor grade. Most of these fusion junctions occur in seemingly random locations. However, transcripts involving fusions of the PTPRZ and MET gene were found repeatedly in clinical specimens derived from different patients. The study estimates that 15 percent of the secondary glioblastoma harbor this fusion.

“The recurrent nature of this fusion transcript suggests that the fusion did not arise by chance. Instead, it’s likely that the fusion actively contributes to the biologic behavior of the tumor,” said Chen, who collaborates with a multidisciplinary team at UC San Diego Moores Cancer Center. “Supporting this hypothesis, we demonstrated that glioblastoma cells expressing the PTPRZ-MET fusion are more invasive and patients afflicted with these tumors showed particularly poor survival relative to other secondary glioblastoma patients.”

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NCI grant awarded to study novel cancer treatment


UC Davis will study combining a novel type of immunotherapy with radiation, chemotherapy.

Robert Canter, UC Davis

A multidisciplinary team at UC Davis will embark on research to determine whether combining a novel type of immunotherapy with radiation and chemotherapy can make treatment for sarcoma, breast and pancreatic cancers more effective.

The work is funded with a $1.7 million, 5-year grant from the National Cancer Institute (NCI) and will involve the UC Davis Laboratory of Cancer Immunology in the Department of Dermatology, Division of Surgical Oncology, Department of Radiation Oncology, as well as the School of Veterinary Medicine.

“We think we have a novel and potentially high-impact treatment that can be developed fairly rapidly for clinical use,” said Robert Canter, associate professor of surgical oncology and a lead researcher on the project. The treatment would combine an immune therapy derived from natural killer cells with traditional drug and radiation therapy.

Sarcoma, breast and pancreas cancers were chosen for the study because they can be aggressive and difficult to treat, and they lend themselves to an approach in which tumor specimens can be examined before and after treatment to determine their efficacy, he said.

Impetus for the study comes from earlier research demonstrating the importance of natural killer cells, which develop in the bone marrow, in helping prevent relapse in patients who undergo stem cell transplants for treatment of leukemia and other diseases. Studies have shown that natural killer cells are important to the body’s natural defenses against virally-infected and malignant cells, and they help to regulate immune cell function.

“We know from studies in bone marrow transplantation that natural killer cells reject hematopoietic stem cells and prevent bone marrow engraftment, so we have hypothesized that natural killer cells can also target cancer stem cells, since there are similarities and shared properties between the hematopoietic stem cells and cancer stem cells,” Canter explained.

Because they are resistant to chemotherapy and radiation therapy, cancer stem cells can repopulate after treatment, causing relapses and cancer spread. The UC Davis researchers will use natural killer cells as a form of immune therapy to attack cancer stem cells.

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