The U.S. Food and Drug Administration announced today the filing of a consent decree against Medtronic, Inc., and two of the company’s officers—S. Omar Ishrak and Thomas M. Tefft —for repeatedly failing to correct violations, related to the manufacture of Synchromed II Implantable Infusion Pump Systems, medical devices that deliver medication to treat primary or metastatic cancer, chronic pain and severe spasticity. [Read more…]
Lung Cancer Rates on the Decline
The rates of new lung cancer cases in the United States dropped among men in 35 states and among women in 6 states between 1999 and 2008 Among women, lung cancer incidence decreased nationwide between 2006 and 2008, after increasing steadily for decades.
The decrease in lung cancer cases corresponds closely with smoking patterns across the nation. In the West, where smoking prevalence is lower among men and women than in other regions, lung cancer incidence is decreasing faster. Studies show declines in lung cancer rates can be seen as soon as five years after smoking rates decline.
The report also noted that states that make greater investments in effective tobacco control strategies see larger reductions in smoking; and the longer they invest, the greater the savings in smoking–related health care costs. Such strategies include higher tobacco prices, hard–hitting media campaigns, 100 percent smoke-free policies, and easily accessible quitting treatments and services for those who want to quit.
“Although lung cancer among men and women has decreased over the past few years,” said CDC Director Thomas R. Frieden, M.D., M.P.H. “too many people continue to get sick and die from lung cancers, most of which are caused by smoking. The more we invest in proven tobacco control efforts, the fewer people will die from lung cancer.”
Lung cancer is the most commonly diagnosed cancer that affects both men and women, and is the leading cause of cancer death in the United States. Cigarette smoking and exposure to secondhand smoke cause most lung cancer deaths in the United States. To further reduce lung cancer incidence, intensified efforts to reduce smoking are needed.
For this report, researchers analyzed lung cancer data from CDC′s National Program of Cancer Registries and the National Cancer Institute′s Surveillance, Epidemiology, and End Results Program. They estimated smoking behavior by state using the CDC′s Behavioral Risk Factor Surveillance System.
Study findings include:
- Among men, lung cancer rates continued to decrease nationwide.
- From 1999 to 2008 lung cancer rates among men decreased in 35 states and remained stable in nine states (change could not be assessed in six states and the District of Columbia).
- States with the lowest lung cancer incidence among men were clustered in the West.
- After increasing for years, lung cancer rates among women decreased nationwide between 2006 and 2008.
- Lung cancer rates decreased between 1999 and 2008 among women in California, Florida, Nevada, Oregon, Texas, and Washington.
- Lung cancer rates among women remained stable in 24 states, and increased slightly in 14 states (change could not be assessed in six states and the District of Columbia).
Source: CDC
Cancer Cost Projected to Top $150 Billion by 2020
Based on growth and aging of the U.S. population, medical expenditures for cancer in the year 2020 are projected to reach at least $158 billion (in 2010 dollars) — an increase of 27 percent over 2010, according to a National Institutes of Health analysis. If newly developed tools for cancer diagnosis, treatment, and follow-up continue to be more expensive, medical expenditures for cancer could reach as high as $207 billion, said the researchers from the National Cancer Institute (NCI), part of the NIH. The analysis appears online, Jan. 12, 2011, in the Journal of the National Cancer Institute.
The projections were based on the most recent data available on cancer incidence, survival, and costs of care. In 2010, medical costs associated with cancer were projected to reach $124.6 billion, with the highest costs associated with breast cancer ($16.5 billion), followed by colorectal cancer ($14 billion), lymphoma ($12 billion), lung cancer ($12 billion) and prostate cancer ($12 billion). [Read more…]
Key Mutation in Acute Myeloid Leukemia (AML) Found
Scientists have discovered mutations in a particular gene that affects the treatment prognosis for some patients with acute myeloid leukemia (AML), an aggressive blood cancer that kills 9,000 Americans annually.
The Washington University School of Medicine in St. Louis team initially discovered a mutation by completely sequencing the genome of a single AML patient. They then used targeted DNA sequencing on nearly 300 additional AML patient samples to confirm that mutations discovered in one gene correlated with the disease. Although genetic changes previously were found in AML, this work shows that newly discovered mutations in a single gene, called DNA methyltransferase 3A or DNMT3A, appear responsible for treatment failure in a significant number of AML patients. The finding should prove rapidly useful in treating patients and may provide a molecular target against which to develop new drugs. [Read more…]
Low Dose CT Benefits Lung Cancer Detection
The National Cancer Institute (NCI) is today releasing initial results from a large-scale test of screening methods to reduce deaths from lung cancer by detecting cancers at relatively early stages. The report shows twenty percent fewer lung cancer deaths seen among those who were screened with low-dose spiral CT than with chest X-ray.
The National Lung Screening Trial (NLST), a randomized national trial involving more than 53,000 current and former heavy smokers ages 55 to 74, compared the effects of two screening procedures for lung cancer — low-dose helical computed tomography (CT) and standard chest X-ray — on lung cancer mortality and found 20 percent fewer lung cancer deaths among trial participants screened with low-dose helical CT. The NLST was sponsored by NCI, a part of the National Institutes of Health, and conducted by the American College of Radiology Imaging Network (ACRIN) and the Lung Screening Study group. A paper describing the design and protocol of the NLST, “The National Lung Screening Trial. [Read more…]
Personalized Blood Tests for Cancer Use Whole Genome Sequencing
Scientists at the Johns Hopkins Kimmel Cancer Center have used data from the whole genome sequencing of cancer patients to develop individualized blood tests they believe can help physicians tailor patients’ treatments. The genome-based blood tests, believed to be the first of their kind, may be used to monitor tumor levels after therapy and determine cancer recurrence.
“We believe this is the first application of newer generations of whole-genome sequencing that could be clinically useful for cancer patients,” says Victor Velculescu, M.D., Ph.D., associate professor of oncology and co-director of the cancer biology program at Johns Hopkins. “Using this approach, we can develop biomarkers for potentially any cancer patient.”
In a report on the work, published in the February 24 issue of Science Translational Medicine, the scientists scanned patients’ genomes for alterations that, they say, most researchers have not been looking for – rearrangements of large chunks of DNA rather than changes in a single DNA letter among billions of others. They call their new approach Personalized Analysis of Rearranged Ends (PARE).
“In sequencing individuals’ genomes in the past, we focused on single-letter changes, but in this study, we looked for the swapping of entire sections of the tumor genome,” says Bert Vogelstein, M.D., Clayton Professor of Oncology, co-director of the Ludwig Institute at Johns Hopkins, and Investigator in the Howard Hughes Medical Institute. “These alterations, like the reordering of chapters of a book, are easier to identify and detect in the blood than single-letter changes.”
Such DNA rearrangements are widely known to occur exclusively in cancer cells, not normal ones, making them ideal biomarkers for cancer.
Using six sets of cancerous and normal tissue samples taken from four colorectal and two breast cancer patients, the Johns Hopkins team used next-generation sequencing methods to catalogue the genome sequence data of each patient. To find DNA rearrangements, the team first identified regions where the number of DNA copies was more or less than anticipated and where sections of different chromosomes fused together. These regions were further analyzed to identify DNA sequences displaying incorrect ordering, orientation, or spacing. A range of four to 15 rearrangements were found in each of the six samples.
After investigators identified DNA rearrangements in patients’ tumor samples, they looked for the same changes in DNA shed from tumors into the patients’ blood. Using blood samples from two of the colorectal cancer patients, they amplified DNA found in the blood and determined that these tests were sensitive enough to detect rearranged tumor DNA in these samples.
Results from such blood tests, they say, could help clinicians detect cancer or its recurrence and inform them on how a patient is responding to cancer therapies. In one colon cancer patient’s example, the scientists found a section of chromosome four fused to a section of chromosome eight. “We developed a biomarker that could span this rearrangement and used a blood test to evaluate biomarker levels as the patient received a variety of cancer therapies,” says Rebecca Leary, a graduate student at the Johns Hopkins Kimmel Cancer Center.
After an initial surgery, the patient’s biomarker levels dropped due to the removal of the majority of the tumor. The biomarker levels rose again, indicating that additional cancer remained in the patient’s body. After chemotherapy and a second surgery, levels of the biomarker dropped substantially, but still showed a small but measurable level of the biomarker. This was consistent with a small metastatic lesion that remained in the patient’s liver.
The investigators envision that PARE-based biomarkers could also be used to determine whether cancer cells are present in surgical margins or lymph node tissue removed during surgery and possibly for diagnosing early disease. “Eventually, we believe this type of approach could be used to detect recurrent cancers before they are found by conventional imaging methods, like CT scans,” says Luis Diaz, M.D., assistant professor of oncology at Johns Hopkins.
The technology used to examine the patients’ genomes will become inexpensive, predicts Velculescu. He says the genome scan cost them about $5,000 per patient, but that sequencing costs continue to drop. CT scans currently cost $1,500 per scan and are limited in their ability to detect microscopic cancers.
“If current trends in genome sequencing continue, PARE will be more cost effective than CT scans and could prove to be more informative,” says Kenneth W. Kinzler, Ph.D., professor of oncology and co-director of the Ludwig Center at Johns Hopkins.
The Johns Hopkins team plans on testing more patient samples and refining their techniques to produce a commercially viable genome-based blood test. They have filed for patents on the technology.
Under a licensing agreement between the Johns Hopkins University and Genzyme, Velculescu, Vogelstein, and Kinzler, are entitled to a share of royalties received by the University on sales of products related to research described in this paper. The terms of these arrangements are managed by the Johns Hopkins University in accordance with its conflict-of-interest policies.
Funding for the research was provided by the National Institutes of Health, The Lustgarten Foundation, the National Colorectal Cancer Research Alliance, and a UNCF-Merck Fellowship.
Source: Science Translational Medicine, (2/24/2010); John Hopkins Medicine
Natural Compound Sceptrin Reduces Cancer Cell Motility
Scientists have discovered that the natural compound sceptrin, which is found in marine sponges, reduces cancer cell motility (movement) and has very low toxicity. Metastasis is one of the deadliest aspects of cancer, so restricting aberrant cell movement is an important step towards advancing treatments. The research was was conducted by investigators at Sanford-Burnham Medical Research Institute (Sanford-Burnham, formerly Burnham Institute for Medical Research) led by Kristiina Vuori, M.D., Ph.D., and published online in ACS Chemical Biology, in collaboration with Phil S. Baran, Ph.D., of The Scripps Research Institute.
The team tested sceptrin in multiple tumor cell types, including cervical, breast and lung cancers. Sceptrin restricted motility in all cell lines. Further tests showed the compound works by limiting the cells’ ability to contract, a critical function for cell motility. The researchers also found that sceptrin synthesized in the laboratory was just as effective at combating motility as the naturally-derived compound.
Given the recently achieved synthesis of sceptrin in multi-gram quantities by the Baran laboratory, sceptrin could prove to be an attractive lead molecule for further preclinical testing and development for therapeutic purposes,” said Dr. Vuori. It may also prove to be a useful research tool in order to elucidate the mechanisms involved in cell motility.”
The researchers cultured growing cancer cells with growth factor to encourage motility. These cells were treated with varying amounts of sceptrin, which was found to be more effective at increased concentrations. Subsequently, the team conducted apoptosis and cell proliferation studies to determine whether these mechanisms accounted for the decrease in motility of sceptrin-treated cells. Other assays determined that sceptrin limits motility by reducing cell contractility.
Souce: ACS Chemical Biology, Sanford-Burnham Medical Research Institute (2/18/2010)
Barriers to Screening May Increase Colorectal Cancer Deaths
Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Despite evidence and guidelines supporting the value of screening for this disease, rates of screening for colorectal cancer are consistently lower than those for other types of cancer, particularly breast and cervical. Although the screening rates in the target population of adults over age 50, have increased from 20-30 percent in 1997 to nearly 55 percent in 2008 — the rates are still too low. An NIH state-of-the-science panel was convened this week to identify ways to further increase the use and quality of colorectal cancer screening in the United States.
“We recognize that some may find colorectal cancer screening tests to be unpleasant and time-consuming. However, we also know that recommended screening strategies reduce colorectal cancer deaths,” said Dr. Donald Steinwachs, panel chair, and professor and director of the Health Services Research and Development Center at the Johns Hopkins University. “We need to find ways to encourage more people to get these important tests.”
The panel found that the most important factors associated with being screened are having insurance coverage and access to a regular health care provider. Their recommendations highlighted the need to remove out-of-pocket costs for screening tests.
Given the variety of tests available, the panel emphasized that informed decisions incorporating personal preferences may help reluctant individuals determine which test’s combined attributes — invasiveness, frequency, and required preparation — are preferable to them, helping them identify and obtain the most palatable test. For example, an individual may choose a more invasive test requiring less frequent follow-up or a less invasive test requiring more frequent follow-up.
Noting differences in screening rates across racial and ethnic groups, socioeconomic status, and geographic location, the panel emphasized the need for targeted strategies for specific subgroups. Compared with non-Hispanic whites, Hispanics are less likely to be screened.
The panel also noted that if efforts to increase utilization are successful, there will be a greater demand for colorectal cancer screening services. Available capacity involves not only facilities and appropriately trained providers, but also support for informed decision making, resources to coordinate screening services and communicate results effectively, and enhanced monitoring practices to ensure that positive results are followed up with colonoscopy. Depending on the scale of increases in screening rates, there may be a need to increase local and national capacity.
In addition to increasing first-time screening rates, the panel also identified the need to ensure that individuals return for subsequent testing at the recommended intervals. A variety of colorectal cancer screening tests are available and different guidelines recommend them at different intervals.
The conference was sponsored by the NIH Office of Medical Applications of Research and the National Cancer Institute along with other NIH and Department of Health and Human Services components. This conference was conducted under the NIH Consensus Development Program, which convenes conferences to assess the available scientific evidence and develop objective statements on controversial medical issues.
The 13–member conference panel included experts in the fields of cancer surveillance, health services research, community-based research, informed decision-making, access to care, health care policy, health communication, health economics, health disparities, epidemiology, statistics, thoracic radiology, internal medicine, gastroenterology, public health, end-of-life care, and a public representative. A complete listing of the panel members and their institutional affiliations is included in the draft conference statement.
In addition to the material presented at the conference by speakers and the comments of conference participants presented during discussion periods, the panel considered pertinent research from the published literature and the results of a systematic review of the literature. The systematic review was prepared through the Agency for Healthcare Research and Quality Evidence-based Practice Centers (EPC) program, by the RTI International-University of the North Carolina Evidence-based Practice Center. The EPCs develop evidence reports and technology assessments based on rigorous, comprehensive syntheses and analyses of the scientific literature, emphasizing explicit and detailed documentation of methods, rationale, and assumptions.
Source: National Institutes of Health (Feb. 4, 2010)
Targeted Therapy Delivers Chemo Directly to Ovarian Cancer Cells
With a novel therapeutic delivery system, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center has successfully targeted a protein that is over-expressed in ovarian cancer cells. Using the EphA2 protein as a molecular homing mechanism, chemotherapy was delivered in a highly selective manner in preclinical models of ovarian cancer, the researchers report in the July 29 issue of the Journal of the National Cancer Institute.
EphA2 is attractive for such molecularly targeted therapy because it has increased expression in ovarian and other cancers, including breast, colon, prostate and non-small cell lung cancers and in aggressive melanomas, and its expression has been associated with a poor prognosis.
“One of our goals has been to develop more specific ways to deliver chemotherapeutic drugs,” said senior author Anil K. Sood, M.D., professor and in the Departments of Gynecologic Oncology and Cancer Biology at M. D. Anderson. “Over the last several years we have shown that EphA2 is a target that is present quite frequently in ovarian and other cancers, but is either present in low levels or is virtually absent from most normal adult tissues. EphA2’s preferential presence on tumor cells makes it an attractive therapeutic target.”
The researchers used a carrier system to deliver chemotherapy directly to ovarian cancer cells. The immunoconjugate contains an anti-EphA2 monoclonal antibody linked to the chemotherapy drug monomethyl auristatin phenylalanine (MMAF) through the non-cleavable linker maleimidocaproyl. Research has shown that auristatins induce cell cycle arrest at the G – M border, disrupt microtubules and induce apoptosis (programmed cell death) in cancer cells.
The investigators evaluated the delivery system’s specificity in EphA2-positive HeyA8 and EphA2-negative SKMel28 ovarian cancer cells through antibody-binding and internalization assays. They also assessed viability and apoptosis in ovarian cancer cell lines and tumor models and examined anti-tumor activity in orthotopic mouse models with mice bearing HeyA8-luc and SKOV3ip1 ovarian tumors.
According to Sood, who is also co-director of both the Center for RNA Interference and Non-Coding RNA and the Blanton-Davis Ovarian Cancer Research Program at M. D. Anderson, the immunoconjugate was highly specific in delivering MMAF to the tumor cells that expressed EphA2 while showing minimal uptake in cells that did not express the protein. In the models, the therapy inhibited tumor growth in treated mice by 85 percent – 98 percent compared to control mice.
“Once we optimized the dosing regimen, the drug was highly effective in reducing tumor growth and in prolonging survival in preclinical animal models,” Sood said. “We actually studied bulkier masses because that is what one would see in a clinical setting where there are pre-existent tumors, and even in this setting the drug was able to reduce or shrink the tumors.”
As for future research with the EphA2-silencing therapy, Sood said, “We are gearing up to bring it to phase I clinical trials. A lot of the safety studies are well under way or nearing completion and we anticipate that this drug will enter clinical trials within the next few months.”
He added that his group is simultaneously conducting preclinical testing on other chemotherapy drugs to determine which agents might combine well with the immunoconjugate used in the current study.
“There is growing interest in molecularly targeted therapy so that we are not indiscriminately killing normal cells,” Sood noted. “The goal is to make the delivery of chemotherapy more specific. The immunoconjugate we used is in a class of drugs that is certainly quite attractive from that perspective.”
Source: University of Texas M. D. Anderson Cancer Center
Chemotherapy Drug Resistance Linked to Genetic Variant in Women with Breast Cancer
Researchers have found links between an individual’s genetics and their response to treatment with chemotherapy. The findings, by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and colleagues, show how a genetic variant, located in the SOD2 gene, may affect how a person responds to the chemotherapy drug cyclophosphamide. Cyclophosphamide is used in the treatment of breast and other cancers.
The SOD2 gene produces a key protein that protects cells from damage by molecules known as reactive oxygen species, or free radicals. Reactive oxygen species are produced by normal cellular processes and the action of some chemotherapy drugs. The findings represent the first preliminary evidence pointing toward a mechanism and a potential biomarker for cyclophosphamide resistance in breast cancer patients. The study appeared online June 9, 2009, in Clinical Cancer Research.
“This study shows how, with the progress of individualized medicine, a diagnostic test may be developed that determines whether a patient has certain genetic variations that may modify the effect of certain chemotherapies,” said study author Sharon Glynn, Ph.D., of NCI’s Center for Cancer Research.
“In the future, such tests may be used to guide the treatment of patients with the SOD2 variation, ensuring that they receive a therapy that is more effective than cyclophosphamide-based therapies,” added senior author Stefan Ambs, Ph.D., also of the Center for Cancer Research.
Most genes in human cells are present in two copies — one inherited from the mother and the other inherited from the father. These gene copies can vary from one another. Some variations in genes play an important role in how a gene is expressed or how its protein product functions.
The variant identified by the researchers in the SOD2 gene affects both the structure and the function of the encoded protein, an enzyme known as manganese superoxide dismutase (MnSOD) and affects the ability of MnSOD to reach its proper location in the cell and its activity level. MnSOD normally functions inside cellular compartments known as mitochondria and helps protect cells from damage caused by reactive oxygen species formed during cellular metabolism. Excessive levels of reactive oxygen species can be toxic to cells. Indeed, some anticancer drugs depend on increased production of reactive oxygen species to kill cancer cells. Furthermore, some studies have indicated that, because MnSOD neutralizes reactive oxygen species, it can modify the effects of chemotherapy drugs. For example, in laboratory and animal models, increased activity of MnSOD protects cells against the toxic effects of doxorubicin, which is a widely used anticancer drug.
In the new study, the research team investigated whether the variation affected survival in two separate groups of women with breast cancer: 248 women in the United States and 340 women in Norway. Some of the women received chemotherapy, and some did not receive chemotherapy. The team first analyzed DNA from the women to determine their genotype, meaning which types of the SOD2 gene they had. The researchers found that, among patients who received chemotherapy, those who had one form had decreased survival and those with another form had the poorest survival. In contrast, the genotype of SOD2 did not affect survival among those who did not receive chemotherapy.
Next, the team looked at the relationship between SOD2 genotype and the type of chemotherapy the women received. The data were analyzed according to which of three types of commonly used chemotherapy drugs were administered: doxorubicin, 5-fluorouracil, or cyclophosphamide. Both doxorubicin and cyclophosphamide generate reactive oxygen species in cancer cells during treatment. The researchers determined that the presence of a particular variant was associated with decreased survival of patients treated with chemotherapy regimens that contained any of the three drugs. However, the most significant effects were found with the drug cyclophosphamide. Women with a distinct variant form of SOD2 and who received cyclophosphamide-containing chemotherapy had the poorest survival.
The research team says more work is necessary to confirm these findings and to examine the precise mechanism by which a genotype influences the response of cancer cells to cyclophosphamide. The team plans to examine the influence of several variations on the resistance to other chemotherapies.
Source: National Institutes of Health (NIH), 6/9/2009