Cutting-Edge Cancer Research In Long Beach At Pacific Shores – Gazette Newspapers http://news.google.com Thu, 02 Oct 2014 14:10:08 GMT Gazette NewspapersCutting-Edge Cancer Research In Long Beach At Pacific ShoresGazette NewspapersWhen most people think of cutting-edge cancer research, they envision the Mayo Clinic, or perhaps a large university hospital. But cutting-edge research a … Read more […]
Immunotherapy could stop resistance to radiotherapy – Cancer Research UK http://news.google.com Wed, 01 Oct 2014 07:20:00 GMT Times of MaltaImmunotherapy could stop resistance to radiotherapyCancer Research UKDr Simon Dovedi, the lead researcher based at The University of Manchester and member of the Manchester Cancer Research Centre, said: “Using the body’s own defences to … Read […]
The New England Journal of Medicine reports positive results of a phase 1 clinical trial of the drug crizotinib against the subset of lung cancer marked by rearrangement of the gene ROS1. In this multi-center study of 50 patients with advanced non-small cell lung cancer testing positive for ROS1 gene rearrangement, the response rate was 72 percent, with 3 complete responses and 33 partial responses. Median progression-free survival – the time it takes for the disease to resume its growth after being slowed by treatment – is estimated at 19.2 months with exactly half of patients remaining on observation for disease progression that has not yet occurred.
Over 200,000 people in the United States are diagnosed with lung cancer annually and advanced stage lung cancer has a 5-year survival rate of only about 2 percent. ROS1 rearrangements are found in approximately 1 percent of lung cancer patients, the majority of whom have never smoked.
“This is a major advance for the clinical treatment of lung cancer,” says Robert C. Doebele, MD, PhD, investigator at the University of Colorado Cancer Center, associate professor of Medical Oncology at the CU School of Medicine, and one of the study authors. Doebele was involved primarily in the characterization of ROS1 gene rearrangements. Additional CU Cancer Center researchers involved in the project include Marileila Varella-Garcia, PhD, who developed a test for the ROS1 rearrangement in patient tumor samples, and Ross Camidge, MD, PhD, who was involved in the clinical testing of crizotinib against both ALK-positive and now ROS1-positive lung cancers.
In fact, current results follow similar activity seen earlier for the drug against lung cancers marked by rearrangement of the gene ALK. Crizotinib earned FDA approval for treatment of ALK-positive lung cancer in 2011. Both ALK and ROS1 are proteins in the family of tyrosine kinases that normally control the behavior of cells; in the case of these rearrangements, the altered genes continuously signal cells to improperly grow, spread and survive, making the cells act cancerous.
As in the case of ALK-positive lung cancer, in which the gene ALK improperly fuses with the nearby gene EML4, in this newly studied subtype of lung cancer, the gene ROS1 fuses with a nearby partner. Tumor samples studied in the current study showed 5 known gene partners for ROS1 fusion and 2 new partners. The most commonly rearrangement was of ROS1 with the gene CD74, but no matter the ROS1 partner, all rearrangements were equally susceptible to treatment with crizotinib.
“This is ongoing work in which the primary goal of this phase one study was to characterize the safety of the drug. Not only was the safety profile promising, but we saw anti-cancer activity that makes us extremely optimistic for future trials,” Doebele says.
In fact, and though it will need to be confirmed by future trials, crizotinib may have an even more durable action against ROS1-positive lung cancer than it does against ALK-positive lung cancer, the disease for which the drug was initially developed and approved. Specifically, median progression free survival for crizotinib against ROS1-positive lung cancer is just more than double the progression free survival for the drug against ALK-positive lung cancer.
Supported in part by Pfizer, by grants from the National Cancer Institute (K12CA086913 to Dr. Doebele; P50CA058187 to Drs. Doebele and Camidge; and P30CA046934 to Dr. Varella-Garcia).
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At the European Society of Medical Oncology annual congress in Madrid, a group from the University of Colorado Cancer Center reported results a phase 1 trial of the drug bevacizumab (Avastin) combined with the experimental immunotherapy drug MPDL3280A against a variety of solid tumors. Results were generally mixed, for example with 40 percent of kidney cancer patients responding but only 13 percent of colorectal cancer patients.
“I think our results show that it’s worth continuing this line of study,” says Christopher Lieu, MD, investigator at the CU Cancer Center and assistant professor of Medical Oncology at the University of Colorado School of Medicine. The study’s principal investigator was Gail Eckhardt, MD, co-head of the Division of Medical Oncology and senior associate director of translational and collaborative research at CU Cancer Center.
“In this as in many cases of modern cancer care, the question may not be whether the drug combination works, but in exactly which patients it is most likely to be most effective. It seemed as if some patients saw benefit from the combination. Now the challenge is discovering the markers that allow us to predict which patients will benefit and those who might do better with a different treatment,” Lieu says.
The drug MPDL3280A is representative of a class of drugs currently receiving focused research attention, meant to allow the body’s immune system to target cancer tissue.
“The immune system does a great job of recognizing and neutralizing foreign materials in the body. The problem is, tumors aren’t necessarily foreign – they are grown from the body’s own tissue and so tend to go unrecognized by the immune system. One promising thread of current cancer research is to help the body recognize and target this cancerous tissue,” Lieu says.
Every year, nearly 90,000 women in the United States are diagnosed with a gynecological cancer. These cancers include cancer of the cervix, uterus, ovaries, vagina, and vulva; treatments include radiation, chemotherapy, and surgeries.
If a woman is diagnosed with this type of cancer she may not think about how it will affect her intimate relationships. However Dr. Saketh Guntupalli, MD, investigator at the University of Colorado Cancer Center and assistant professor in the Division of Gynecologic Oncology at the CU School of Medicine, has found that there may be a negative impact on sexual health after treatment for gynecological cancer.
“Typically patients do well after treatment,” says Guntupalli. “However some of them found that they have problems with sexual function.”
Guntupalli became interested in exploring sexual dysfunction after cancer treatment when he noticed an increase of couple dissatisfaction and divorces in some of his patients. He was granted $80,000 by the Patty Brisben Foundation for the pilot study.
“This is a subject that no one has really looked into,” explains Guntupalli. “However it is a very real problem for women going through cancer treatment.”
The first step of the study is to gather as much information as possible from patients who are willing to participate.
“We have put together surveys and sent them out to local patients as well as different locations around the United States including Los Angeles and New York,” Guntupalli explains. “We want to find out how cancer treatments affect sexual dysfunction in women all over the nation.”
Dina Flink, a research coordinator in the Guntupalli lab, has been a key player in writing and sending out surveys to patients across the United States.
“The survey that we put out is a sexual health survey,” Flink explains. “It helps us measure things such as satisfaction, sexual function, and how intimate bonds are affected by cancer treatment.”
Once enough information is collected the next step is to figure out what type of intervention is needed for couples going through a cancer diagnoses. Preliminary ideas such as support groups and pre-treatment counseling may help couples keep their bond strong during and after treatment.
“I believe that this is important because here at the CU Cancer Center there is a strong emphasis on survivorship and quality of life after cancer,” says Flink. “We want to help people lead normal lives after treatment.”
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High-grade gliomas (HGG) are brain tumors that are usually fatal in children. Dr. Green’s work has recently shown promising results using a new medicine called Selinexor in laboratory models of HGG. His next step in the project, with the support of the St. Baldrick’s Fellowship, will be a clinical trial of Selinexor to determine a safe dose of the medication in childhood cancer patients, and to look for early signs of efficacy in HGG, as well as other brain and solid tumors.
“We are very excited about the potential of this work to provide a new, safe, and effective treatment to children who currently have very few good options,” said Dr. Green. “We believe that Selinexor works to restore the function of proteins that act as the ‘brakes’ in cancer cells, which would be unprecedented in cancer treatment, and we will have the opportunity to learn more about this mechanism as part of the trial as well. I am personally very grateful to St. Baldrick’s for supporting young researchers to help us launch our careers in finding better treatments for kids with cancer.”
Through the vigorous efforts of volunteers and supporters in the U.S. and around the world, the Foundation is not only honored to award this local grant, but will fund a total of more than $24.7 million to institutions across the country in its 2014 summer grant cycle.
To learn how you can get involved visit www.StBaldricks.org, and connect with St. Baldrick’s on social media via Facebook, Twitter, YouTube and Vimeo.
About St. Baldrick’s Foundation
The St. Baldrick’s Foundation is a volunteer-driven charity committed to funding the most promising research to find cures for childhood cancers and give survivors long and healthy lives. Since 2005, St. Baldrick’s has awarded more than $152 million to support lifesaving research, making the Foundation the largest private funder of childhood cancer research grants. St. Baldrick’s funds are granted to some of the most brilliant childhood cancer research experts in the world and to younger professionals who will be the experts of tomorrow. Funds awarded also enable hundreds of local institutions to participate in national pediatric cancer clinical trials. For more information about the St. Baldrick’s Foundation please call 1.888.899.BALD or visit www.StBaldricks.org.
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The University of Colorado Cancer Center announces today a research collaboration with NantBioScience for the development and commercialization of anti-cancer agents designed to target the Ral protein, a cell signaling protein implicated in the growth and spread of cancer. The announcement follows this week’s publication in the journal NATURE of an article describing a novel approach to targeting Ral protein activation, and drug candidates that may block this activation.
Although the Ral protein has been found to play a role in the most commonly activated signaling pathways across cancer types, including colon, lung and pancreatic cancers, it has not yet been successfully targeted for potential therapeutic intervention. The CU Cancer Center’s partnership with NantBioScience is focused on the development of clinical compounds designed to block the function of the Ral protein.
“NantBioScience is committed to the discovery and development of cancer fighting therapies that target the key drivers and root causes of tumor growth and spread. Targeting the Ral protein expands our ongoing efforts to silence a key pathway, the RAS pathway, that has been found to be altered and constitutively activated in one out of three cancers,” said Shahrooz Rabizadeh, PhD, Chief Scientific Officer of NantBioScience. “We are pleased to be partnering with the University of Colorado, leaders in the science of inhibiting Ral function, to accelerate the development of novel cancer medicines for patients.”
Through structural and computational analysis, compounds that block the activity of Ral were identified by Dan Theodorescu, MD, PhD, and colleagues, demonstrating the feasibility of developing potential treatments for this target. This pursuit of a clinical product targeting Ral is a collaborative effort, with teams from both the CU Cancer Center and NantBioScience conducting research activities together.
“We are excited to partner with NantBioScience to one day bring our basic research of Ral protein inhibitors to the beside of patients in the form of a new cancer fighting treatment,” says Theodorescu, director of the CU Cancer Center and senior author of the recent NATURE article.
“This collaboration with Dr. Dan Theodorescu and the University of Colorado Cancer Center furthers our goal to catalyze personalized precision cancer care in our war against cancer,” said Patrick Soon-Shiong, MD, CEO of NantBioScience.
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Dressed in teal and enjoying breakfast and visionary talks from leading women’s cancer researchers, 65 patients, supporters and community members helped kick off Gynecologic Cancer Awareness Month with collective enthusiasm for the future.
On Sept. 6, the strength and vision of the University of Colorado Cancer Center’s Program of Excellence in Gynecologic Cancer (PEGoC) was on full display as guests to the Anschutz Medical Campus attended a first-of-its-kind symposium focused on women’s cancer research at CU.
Saketh Guntupalli, MD, assistant professor in the Division of Gynecologic Oncology, welcomed the crowd and introduced David Mutch, MD, who spoke about the state of gynecologic oncology research from a national perspective. Dr. Mutch is professor and division chief of Gynecologic Oncology at Washington University in St. Louis and a well-known expert in the field.
Kian Behbakht, MD, professor and division chief of Gynecologic Oncology at the University of Colorado presented on the current state of care, research and education here on the Anschutz Medical Campus. He also explained the need for immediate and long-term funding for CU’s Gynecologic Oncology Fellowship Program, as training new gynecologic oncologists is critical for women’s health – especially in Colorado, a state with only 11 physicians currently practicing in this subspecialty.
“Women diagnosed with cancer of the reproductive organs have significantly better outcomes and survival rates when seen by a trained gynecologic oncologist,“ said Behbakht. “Every woman should have access to a gynecologic oncologist when facing these cancers. In order to make this a reality, however, we need to put more resources into fellowship programs like the one here at the University of Colorado, to train the next generation of gynecologic oncologists and to ultimately save more lives.”
Carol Goldstein, RN, PhD, a dedicated volunteer, echoed the call for more training of gynecologic oncologists, which she explained was critical to her own positive outcomes as a patient at the CU Cancer Center. Goldstein urged attendees to join her and her husband in supporting the fellowship program at CU as a way to improve the future for women who seek treatment at the CU Cancer Center.
After the talks, guests were invited to tour one of the gynecologic oncology research labs on campus. Posters were also on display highlighting the research being done by the current fellows.
The event was hosted by the Gynecologic Oncology Community Council, a collection of dedicated supporters of PEGoC, which includes:
- Carol Goldstein, RN, PhD
- Donna Mullen Good
- Bettina Kurowski
- Katie Reinisch
- Bobbi Siegel, MSW
- Suzanne White
About the Program of Excellence in Gynecologic Cancer
The Program of Excellence in Gynecologic Cancer (PEGoC) is a far-reaching, ambitious effort with the goal of helping eradicate the serious impact, consequences and cost of gynecologic cancer in the Rocky Mountain region. With its five-pronged approach–Prevention, Research, Detection, Treatment and Outreach–PEGoC is unique in its ability to address these important issues with one comprehensive coordination program. PEGoC is a program of the University of Colorado School of Medicine, Anschutz Medical Campus, Division of Gynecologic Oncology, and is located at the University of Colorado Cancer Center at the Anschutz Cancer Pavilion in Aurora.
About the CU Gynecologic Oncology Fellowship Program
In 2013, over 95,000 women were diagnosed with gynecologic cancer in the United States. Yet many women who need high-quality care do not have access to a gynecologic oncologist. An insufficient number of young doctors become gynecologic oncologists primarily because there are now only a few robust fellowship/training programs like the one at the University of Colorado. “Fellows” in the Gynecologic Oncology Division in the CU Department of Obstetrics and Gynecology receive the country’s best training and education alongside some of the most renowned oncologists in the world.
The goals of the Gynecologic Oncology Fellowship Program are: 1) To educate obstetrician-gynecologists in the comprehensive care of women with cancer of the reproductive organs, and 2) To foster the development of future physician-scientists and leaders within the field of gynecologic oncology.
Gifts to support the endowment for this program, ensuring that it will be sustainable for many, many years to come, can be made at www.cufund.org/GynOncEndowedFellowship
The post A Teal Saturday: Gynecologic Cancer Symposium at CU appeared first on Colorado Cancer Blogs.
The story of cancer care seems so simple: find the mutated gene that causes cancer and turn it off or fix it. But rarely does a single gene cause cancer. More often, many genes are altered together to drive the disease. So the challenge becomes sorting out which altered genes are the most to blame in which cancers. A collaborative study between researchers at the University of Colorado Cancer Center and the National Cancer Institute (NCI) published today in the journal Clinical Cancer Research takes an important step toward answering this question in bladder cancer.
Specifically, the study examined a mutation-rich layer of the genome called the exome of 54 bladder tumors from primarily Caucasian patients. The study is the first to show alterations in the gene BAP1 in 15 percent of tumors; the gene is a likely tumor suppressor and so bladder cancers with alterations in this gene may be without an important check on the growth and survival of bladder cancer tissue.
Somatic BAP1 alterations contribute to a high frequency of tumors (10/14, 71 percent) with defects in genes encoding BRCA1 and BRCA2 pathway proteins, pathways that have been previously implicated in breast and other cancer types.
More surprising, a second, highly independent genetic pathway was found in 69 percent of 54 tumors, in which alterations of the TERT promoter created what is effectively a second subset of bladder cancer. The TERT promoter mutations did not significantly correlate with somatic alterations in other cancer genes, indicating that this alteration confers a presumed oncogenic benefit independent of other cancer gene alterations.
The gene KDM6A was frequently altered in 24 percent of tumors, and the study shows that experimental depletion in of KDM6A in human bladder cancer cells enhanced in vitro proliferation, in vivo tumor growth, and cell migration, confirming its role as a cancer driver and tumor suppressor in bladder tissue.
The study revealed other surprising relationships between the types of genetic alterations in bladder tumors. BAP1 somatic mutations may correlate with papillary features in some bladder tumors and were significantly more frequent in Caucasian patients than Chinese patients, indicating ethnicity, lifestyle, or exposure may influence somatic BAP1 mutations. BAP1 and KDM6A mutations significantly co-occurred in tumors, indicating they likely supply mutually reinforcing survival advantages to cancer cells. Finally, just four genes encoding chromatin remodeling enzymes, BAP1, KDM6A, ARID1A, and STAG2, were altered in 46 percent of 54 tumors and demonstrate a major contribution from somatic alterations targeting chromatin remodeling functions in bladder cancer.
“Taken together, we have identified new subtypes of bladder cancer that are related by somatic and germline genetic alterations that are observed in patient tumors. These subtypes may be vulnerable to subtype-specific therapeutic targeting. For example, many tumors in this study possessed cells with mutations targeting the BRCA DNA repair pathway indicating they are likely to be deficient in their ability to repair DNA,” says Dan Theodorescu, MD, PhD, professor of Urology and Pharmacology, director of the University of Colorado Cancer Center and the paper’s senior author.
“Thus the tumor cells should be especially sensitive to chemotherapeutic drugs that create DNA damage. This is an excellent example of a case in which basic science can now suggest targeted treatments that have the real possibility to benefit patients,” says Michael Nickerson PhD, staff scientist and lead author from the National Cancer Institute.
Supported in part by NIH grants CA075115 and CA104106, and by the NCI Intramural Support Program
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AURORA, Colo – On September 10, at the invitation of Rep. Diana DeGette (D), Dan Theodorescu, MD, PhD, director of the University of Colorado Cancer Center, took part in a panel on the future of biomedical innovation in the United States and what can be done to get new, effective treatments to people who need them. The panel, in Washington, DC, also included Dr. Francis Collins, director of the National Institutes of Health, Sylvia Burwell, secretary of the U.S. Department of Health and Human Services, Margaret Hamburg, commissioner of the U.S. Food and Drug Administration, the inventor Dean Kamen, and the philanthropist Michael Milken.
The 21st Century Cures Roundtable was the last in a series of roundtables sponsored by DeGette, a Democrat from Denver, and Rep. Fred Upton, a Republican from Michigan. DeGette and Upton sit on different sides of the aisle but share an interest in ensuring that the United States remains the world’s innovator in healthcare and biosciences. The purpose of the panel was to gather expertise from leaders in the field of health care innovation and personalized medicine to shape the future of medicine in the U.S.
Specifically, Dr. Theodorescu used his perspective as one of the country’s top cancer researchers to contribute the point of view that the U.S. is in danger of losing its biomedical edge to countries that are aggressively funding research into personalized medicine.
“Personalized and precision medicine and how we do it is really the central challenge of our moment in time,” said Theodorescu. “The United States has built an incredible genomic engine and infrastructure and has resulted in a lot of technology to really push forward biotechnology in medicine. It would be a shame now to not capitalize on that.”
Encouraged by DeGette, Congress is taking a comprehensive look at what can be done to accelerate the pace of cures in the United States. She is working with colleagues to draft legislation that will address the biomedical process—from the basic-science discovery phase to streamlining drug and device development to delivering personalized, targeted treatments to patients.
According to Theodorescu, part of the system overhaul of bringing cures from biology to bedside is rethinking the process for clinical trial patient consent, which he knows from extensive experience is too costly and complicated. In Theodorescu’s opinion, a centralized institutional review board could bring trials to patients quicker and more efficiently. (Currently, clinical trials must be approved at each institution enrolling participants, leading to lengthy reviews.)
“Patients are the heart and soul of personalized medicine. We really rely on them. We are eternally grateful for their participation,” said Theodorescu. “We need to encourage [patients] to participate, which means removing barriers.”
According to Theodorescu, easing participation in clinical trials also removes barriers for young scientists. “People that want to do translational research in medicine have to have a clear career path and have to be able to spend their time getting trials done, getting patients on trial. If the barriers to accruing patients are so high, then we’re going get progressively fewer young investigators wanting to embark on those careers,” Theodorescu says.
Interdisciplinary panels such as this that bring together leaders in their fields – from policy to science to philanthropy and beyond – ensure that the most informed voices are heard as we move from yesterday’s era of one-size-fits-all care and into the future of truly personalized medicine.
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