How A Nasty, Brain-Eating Parasite Could Help Us Fight Cancer

How A Nasty, Brain-Eating Parasite Could Help Us Fight CancerWe’ve known since the turn of the 20th century that some infectious diseases are a major risk for developing specific cancers. More worryingly, about one-sixth of cancers worldwide are attributable to infectious agents. Globally, more than 2m cancer cases are linked to certain carcinogenic viral, bacterial or parasitic agents. Two-thirds of these occur in developing countries.

Although we’ve been aware of the connection between parasites and cancer since before the 18th century, we’re increasingly linking certain parasites to an increased risk of developing specific forms of cancer. For example, the fish-borne parasitic worms Opisthorchis viverrini and Clonorchis sinensis have been linked to increased risk of developing cancer of the bile duct (the tube that connects the liver to the intestines). Also, infection with the parasitic wormSchistosoma haematobium can cause bladder cancer. Worldwide, these three parasitic infections accounted for 8,300 new cancer cases in 2012.

Infections can lead to cancer by directly manipulating the genes that control growth of the affected host cell – causing the cell to grow out of control. They can also cause cancer through long-term inflammation that leads to changes in the affected cells and in nearby immune cells or by suppressing a person’s immune system that normally helps protect the body from some cancers. But we also know that the body’s own immune defences can be used to fight tumour cells. And now a new study suggests that a brain-eating parasite that has been incriminated in cases of brain cancer can be reprogrammed to treat ovarian cancer.

The team of investigators behind the new study set out to harness the immune system’s reaction to the presence of the parasite Toxoplasma gondii (T. gondii), which can be found in cat faeces, as a tool to cure ovarian cancer. Specifically, they identified specific proteins secreted by T. gondii that enable the immune system to attack established ovarian tumours in mice. This involved uncovering parasite specific proteins and associated host mechanisms that are important for the development of potent antitumor responses. The researchers deleted genes for proteins that the parasite injects into a host cell to modulate cell functions and immune response during infection. They also used the genetically altered parasites to vaccinate mice with aggressive ovarian cancer.

The results showed that active parasite invasion along with specific proteins secreted before and after penetration of mouse cells elicited an antitumour response and increased survival by at least 40 days (mice only live a couple of years) compared to non-vaccinated mice. While surviving a longer period with cancer can be considered as an improvement, these results should be handled carefully because vaccinated mice didn’t get rid of the cancer completely and we do not know how this treatment could affect tumour regression in humans.

Terrifying Bug

In the field of parasitology no single parasite is as popular as T. gondii. This single-cell parasite, which affects one third of the world’s human population, is best known for its ability to invade and damage the brain and alter the behaviour of affected individuals. Long before the Zika virus became a serious concern for expectant mothers, infection with T. gondii was terrifying not only to pregnant women, but also to individuals with seriously compromised immune systems, such as HIV/AIDS patients or patients on cancer therapies. This parasite can be passed along from mothers to the fetus, putting the developing babies at risk of severe neurological and vision disorders. It is very intriguing that what used to be a disturbing infection could potentially now be the remedy for an even more terrifying disease.

The idea of turning immune defences, elicited by parasitic infection, against illnesses is not new. Some worms have been shown to lessen susceptibility to type 1 diabetes and other autoimmune and inflammatory diseases, as well as to promote wound healing. However, the potential of exploiting the immune responses associated with T. gondii to help the immune system recognise and attack ovarian cancer, which is difficult to treat, is definitely out-of-the-box thinking and deserves to be commended. The same group of investigators has previously shown that the use of attenuated T. gondii can generate longlasting immunity that protects against the recurrence of disseminated pancreatic cancer. But it is early days and much more work needs to be done to determine if a similar mechanism happens in humans.

As more is learned about the dynamic cross-talks between this parasite, immune cells and tumours it may be possible that T. gondii or some of its proteins can one day become a real remedy that can be used to cure ovarian cancer and hopefully other forms of cancer, too.

To read this entire article on MedicalXpress.com, please click here.

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The ‘Fatal Attraction’ of an Ovarian Cancer Test

The 'Fatal Attraction' of an Ovarian Cancer TestUse of a blood test in the monitoring of ovarian cancer patients who are in remission is an example of the “fatal attraction of more information” in medicine, according to an editorial published July 21 in JAMA Oncology.

The commonly used cancer antigen 125 (CA-125) test is irresistibly and destructively attractive to both oncologists and patients, suggests editorialist James Goodwin, MD, from the University of Texas Medical Branch, Galveston.

He explains that the routine use of the CA-125 test was proven to be “harmful” in this setting in a major clinical trial in 2009 ( ASCO Ann Meet Proc. 2009;27[18s]:1).

In that trial, patients randomized to routine CA-125 testing had no better survival and worse quality of life compared with patients who were randomized to clinical observation (and did not receive test results) because, overall, the test results triggered earlier second-line chemotherapy, which was not efficacious.

Now, 7 years later, a new study has been published as follow-up on this subject — to learn if the evidence from 2009 changed practice.

This new study, also published online in JAMA Oncology, prompted Dr Goodwin’s “fatal attraction” comment in the accompanying editorial.

The researchers, led by Katharine Esselen, MD, MBA, from Harvard Medical School in Boston, reviewed the use and frequency of CA-125 testing in 1241 women in remission after initial treatment of ovarian cancer at six National Cancer Institute-designated cancer centers from 2004 to 2011.They found that almost all of the study’s patients received CA-125 testing every 3 to 4 months, both before and after the 2009 study.

In short, the 2009 study results did not change CA-125 testing.

This becomes the leaping off point for Dr Goodwin’s editorial as he asks: “Why did practice not change?”

Physicians are capable of “rapid change in practice in the face of new information,” he says.

He cites an example: When a study showed an absolute survival improvement of 2% at 18 months after treatment with a taxane plus doxorubicin compared with doxorubicin alone in node-positive breast cancer, there was a doubling of use of the combination therapy within 3 months of an oral report of the findings (J Natl Cancer Inst. 2006;98[6]:382-388).

Dr Goodwin then proposes that two sets of factors contribute to the lack of change after the 2009 ovarian cancer study; the first is “the fundamental attractiveness of testing.”

“Physicians practice in a sea of uncertainty. Making life-altering decisions based on incomplete information is one of the major stresses of becoming a physician,” he writes. Thus physicians seek “more information through testing to reduce uncertainty.

This seems benign, suggests Dr Goodwin, who asks, “How could more information possibly hurt?” He also says that avoiding information “sounds antiscientific” and doctors are confident that they can interpret results “wisely.”

But these sentiments are not borne out by the new study.

When CA-125 tests revealed increased levels, second-line chemotherapy was initiated equally rapidly after and before the 2009 study results. And those results showed that this management (test followed by second-line chemotherapy) was inconsequential in terms of survival and detrimental to overall well-being.

This is where the metaphor of fatal attraction, which is a reference to a 1987 film about an extramarital affair, applies. Dr Goodwin suggests that the object of clinicians’ desire (in this case, a test result) can destructively backfire.

In discussing the second set of factors influencing the lack of practice change, Dr Goodwin faults the authors of the 2009 study results for not effectively “framing” the results of the study.

He explains that the approaches examined in the study were characterized as early versus delayed chemotherapy instead of CA-125 surveillance testing every 3 months versus no testing information.

“The findings of the study are then best framed as routine surveillance with CA-125 testing is harmful in patients diagnosed with ovarian cancer in remission after initial treatment,” he writes.

Patients and Their Needs Play a Role

Dr Esselen and her coauthors also have some thoughts about why the 2009 study results “may not have been widely embraced.”

Importantly, national guidelines on CA-125, “do not consistently advise against surveillance testing,” they observe.

Indeed, the 2015 National Comprehensive Cancer Center Network’s clinical guidelines recommend routine CA-125 testing for patients whose CA-125 levels are elevated at diagnosis. Also, the Society for Gynecologic Oncology categorizes CA-125 testing as optional. The American Society of Clinical Oncology recommends stopping surveillance testing in some asymptomatic patients.

CA-125 testing may also offer benefits that the 2009 study did not examine, say Dr Esselen and coauthors.

“Specifically, patients and physicians may be reluctant to stop CA-125 testing because it may offer a relatively inexpensive, patient-centered approach to maximize treatment options by identifying recurrent disease before irreversible complications ensue that might limit opportunities for eligibility for clinical trials or secondary cytoreductive surgery,” they write.

Thus CA-125 testing may be a “rational, values-based decision” to guard against the worst-case scenario of disease progression.

The authors also comment that both patients and physicians “may share a bias toward therapeutic action.”

In their paper, the authors also discuss the economic impact of continued CA-125 testing, but in his editorial Dr Goodwin says that he is uncomfortable with this focus. “In the context of CA-125 testing, the issue of cost effectiveness becomes absurd. How can a test or treatment be cost-effective if it is not effective — indeed, if it is harmful?” he writes.

The CA-125 test is relatively inexpensive test (Medicare reimbursement is $28). The cost is “not by any means irrelevant but it muddles the issue,” the editorialist writes.

Dr Goodwin says that patients play a role in decision-making about CA-125 testing. “While physicians may be challenged dealing with uncertainty, many of our patients refuse absolutely to tolerate it…even if that knowledge can lead to harm.” Most patients choose more clinical information when it is offered, he says.

Dr Goodwin does not think that the practice of routine CA-125 testing will likely stop, and believes that the controversy may “fade away.”

In conclusion, he writes that the testing will probably continue:”The fatal attraction of more information is too compelling.”

However, Dr Esselen suggests that the test has a place in ovarian cancer management.

In a press statement, she said: “It’s very easy to talk about CA-125 testing on a grand scale and its lack of impact on overall survival,” she said. “But when there’s an individual who has a history of ovarian cancer sitting in front of you, it’s a completely different story.”

To read the full article published on Medscape.com, please click here.

Making Medicine More Precise, Accessible

Making Medicine More Precise, Accessible

Medical science is more advanced than at any point in history. Yet the health care system — medical science applied to actual patients — still leaves many people without the best and latest treatments.

For example, new knowledge about health and disease accumulates in research labs at an accelerating rate. Genomics explores the effects of DNA variations. Proteomics examines the roles of proteins. The microbiome, the set of microscopic creatures living on and in us, is increasingly linked to well-being. And environmental influences affect all of these other factors, for good or ill.

But amid this torrent of discoveries, there’s a growing backlog in trying to put them into action. The innovations remain stuck in the laboratories or kept within elite medical institutions, left untranslated into medications, equipment and other therapies that would help doctors, health insurers and the public.

Fixing the bottleneck has become its own branch of medical science. The young but exploding field is known by various names that emphasize various nuances — translational medicine, personalized medicine, individualized medicine and precision medicine.

These terms point toward the same goals: Making medicine more effective by creating smoother and quicker paths for commercializing lab discoveries, plus tailoring those new products and technologies to the many different types of patients.

“In its simplest terms, it’s the right drug for the right patient at the right time,” said Damian Doherty, editor of a new publication devoted to the field — the Journal of Precision Medicine. His peer-reviewed journal joins an expanding field of similarly focused titles.

It sponsored the Precision Medicine Leaders Summit this month, drawing experts from around the country to downtown San Diego for spirited discussions about the field’s biggest hopes and biggest hurdles.

//players.brightcove.net/15364600001/default_default/index.html?videoId=5089464948001Tremendous changes have already taken place.

With the use of “big data” and other powerful information technologies, more genetic variations linked to cancer are being identified. Patients’ genomes are screened against drugs such as the blood thinner Plavix to determine if those medications will be effective, a practice pioneered by the local Scripps Health network.

Such testing is also occurring at Rady Children’s Institute for Genomic Medicine in San Diego. Infants and children with undiagnosed diseases are screened there in a bid to find treatments for them. Dr. Stephen Kingsmore, president and CEO of the institute, discussed at the summit how the life of an infant who had seven days to live was saved by this kind of diagnosis.

The summit’s participants also dealt with practical challenges.

These include how to get more Americans from diverse racial, gender and age categories to enroll in clinical trials. Also, how to maximize collaboration between scientific institutes, biotech companies and pharmaceutical giants so there’s a streamlined process for turning lab findings into usable drugs and products.

And the summit’s attendees took on the difficult issue of disparities in access to the most advanced and comprehensive care. In other words, how can experts help patients in poor communities or those living far away from a major medical center secure the chance to try groundbreaking or experimental treatments?

Underlying all of these speeches and forum panels was the omnipresent theme of economics. Can the government, hospitals, physicians, drug companies, scientists and others take advantage of precision medicine to control medical costs while raising the quality of care?

The advantages are too great not to pursue precision medicine, said Euan Ashley, a Stanford University Medical Center associate professor of medicine and genetics, in an article last week in Nature Reviews Genetics.

“Fueled by technological advancement, fundamental discovery of genetic elements related to health and disease has been the engine of human genetics for decades,” Ashley wrote. “Building on this foundation, precision medicine will use the knowledge gained to redefine disease, to realize new therapies and to provide hope for generations of patients to come.”

That’s the vision. At the summit, experts in precision medicine outlined a path to getting there.

Government Efforts

The federal government during President Barack Obama’s tenure and California during Gov. Jerry Brown’s latest terms have committed to advancing precision medicine. These efforts have largely involved fostering coordination among the wide-ranging groups with a stake in the field.

Money hasn’t necessarily been a big part of the governmental investment. California’s initial contribution to precision medicine, announced in 2014, was just $3 million. And the Obama administration’s push came with a relatively modest injection of $215 million.

More important, making precision medicine an official priority gave it a stamp of approval, indicating that this was the direction health care would take. The goal is to get those in all aspects of medicine to understand that they have a role to play, said Dr. Elizabeth Baca, a senior health care adviser in Brown’s Office of Planning and Research.

“It’s not just in one program or one area,” Baca said at the recent summit in San Diego. “It’s about a different approach to disease … the knowledge network, environment, lifestyle. It’s not just about the genes.”

While the $3 million wasn’t a formidable sum, Baca said it served to prompt discussions about how those involved in medicine could use the resources they already have more effectively through translational science.

“We talked with a lot of thought leaders in this space from private sector venture capital, academia, patient groups, to think about what we could do in California,” Baca said.

Since all of this planning is supposed to wind up helping patients, any project adopted by the initiative will be measured for results, Baca said. A benefit to patients needs to show up within two years.

One project selected for funding is to speed up diagnosis of infectious diseases by examining body fluids from the spine and elsewhere for the presence of infectious agents. The fluids are screened for the presence of genetic material from a panel of known pathogens. This technology has already been used to diagnose a disease that numerous tests couldn’t find, Baca said.

The California program’s website is www.ciapm.org.

At the federal level, Obama’s campaign, called the Precision Medicine Initiative, was unveiled in January 2015.

Components include enlisting at least 1 million volunteers to provide their health and genetic information, finding genetic variants that fuel cancer and develop better therapies against them, building high-quality databases and formulating better technology for transmitting data across different networks.

Recruiting the 1 million-plus volunteers started last month.

Safeguarding the privacy of volunteers’ personal information from hackers and others is obviously a concern, said Fae Jencks, a White House adviser with the initiative. The White House is asking the public for suggestions on what it would like to see in terms of data security for such medical projects.

The initiative’s website is whitehouse.gov/pmi.

Since there’s less than half a year left in the White House for the Obama administration, officials have worked to ensure the initiative continues long term, Jencks said. Survival odds look good because Congress has given bipartisan support to the initiative.

The initiative’s work at the National Institutes of Health, the nation’s dominant source of funding for life sciences, is directed by scientist Eric Dishman. The former Intel executive joined the NIH in April. Since he is not a political appointee, Dishman’s job continues even after Obama leaves office, Jencks said.

 

Making Medicine More Precise, AccessibleCancer

While precision medicine can be used for all diseases, cancer is among those in the most need of better approaches. Uneven progress against cancer provides one of the greatest frustrations for researchers, and it was a major topic at the Precision Medicine Summit.

Underlying the frustration is cancer’s great complexity. It’s not just one disease, but more like many diseases with many different causes. Uncontrolled cell growth is the common factor.

Some forms are easily treatable, such as choriocarcinoma, or cancer of the placenta. This cancer was nearly 100 percent fatal before the discovery of chemotherapy. With chemotherapy, it’s more than 90 percent curable.

Other forms are mostly incurable even today. These include pancreatic cancer, which killed Apple co-founder Steve Jobs at the age of 56. Its five-year survival rate is just 7 percent, according to the American Cancer Society.

Still other cancers, such as ovarian cancer, often initially respond to treatment but tend to recur and metastasize. Subsequent treatments become progressively less effective, and patients often die of the recurrence. Not surprisingly, there’s an urgent push to find more effective drugs for resistant and metastatic cancers, and to get experimental drugs to patients in greatest need.

Many of these newer drugs target genetic disorders specific to tumor cells in particular patients. And existing drugs are being further examined to find out if they may work against other cancers than the ones they are approved to treat.

It’s a promising approach, UC San Diego oncologist and researcher Razelle Kurzrock said at the summit. Kurzrock is co-founder of CureMatch, a San Diego company that makes software that guides doctors in choosing the best course of cancer treatment.

“I genuinely believe that genomics and other ‘omics’ is bringing us the ability to match patients with the best drugs,” Kurzrock said. “What they are telling us is the classical way of doing clinical trials and practice doesn’t work well. And we need to do things differently in order to transform care.”

That transformation must overcome considerable inertia, Kurzrock said.

“We’ve built this enormous way of doing things that we’ve been doing for decades, and the science is saying we need to do things differently,” she said. “For cancer patients with metastatic disease, we need to move to combination therapy. Single agents are unlikely to get very far with these patients.”

Advanced approaches to cancer therapy need to be used earlier in the disease.

“Right now, we’re using them almost exclusively for end-stage patients,” Kurzrock said. “That’s really too late.”

The Clearity Foundation, a San Diego nonprofit, specializes in matching the best drugs to ovarian cancer patients with recurrent tumors. Through partners, Clearity arranges for tumor samples to be genetically analyzed and compared with those of others in a tumor database of hundreds of tumor samples.

Results are summarized in a “tumor blueprint” that indicates which drugs have had the best effect against that tumor’s genetic profile. This can help doctors and patients decide which drugs to try, whether recommended for the cancer, or an “off label” use, or perhaps an experimental drug.

Clearity provides these services free of charge.

 

Making Medicine More Precise, AccessibleAdding To Arsenal

Meanwhile, discoveries continue to roll out, illuminating the molecular roots of cancers.

In June, scientists led by Kurzrock’s fellow researcher and oncologist Catriona Jamieson published a study in the journal Cell Stem Cell that showed how precursor cells to leukemia transform into actual leukemia stem cells — and how that process can be stopped.

The culprit is an enzyme called ADAR1 that edits RNA. In certain leukemias, precursor cancer stem cells become sensitive to inflammation, which causes increased production of ADAR1. That enzyme changes the sequence of genetic molecules called microRNAs.

In turn, the altered microRNAs cause the precursor cells to grow more rapidly, precipitating a dangerous turn of events known as “blast crisis.”

Jamieson said the discovery could be used in the near-term to monitor and predict the progression of leukemia. In the longer term, a drug that can stop the process could be developed to treat ADAR1-sensitive leukemia.

The final link in this process of research for new drugs and development of new ways to use them is to actually get the drugs to patients.

Surgical oncologist Timothy Yeatman told summit participants the clinical trial locations for testing new cancer therapies are inconvenient for many patients who could benefit. These trials tend to cluster in prestigious hospitals in big cities, posing a burden on patients who live far away or who are being treated in community hospitals.

Since 85 percent of cancer care is delivered in these community settings, there’s enormous room to improve patient access, said Yeatman, director of Gibbs Cancer Center. The center is located in Greer, a city of about 27,000 between Greenville and Spartanburg in South Carolina.

Automating start-ups and centralizing contracting can help these community hospitals take part by cutting the needed labor and time, he said.

“You can open a trial up in 17 days from receipt (of authorization) like we did last week,” Yeatman said.

By teaming with community hospitals and their patients, clinical trial sponsors such as drug companies also benefit, Yeatman said, citing a Forbes article on money lost from trials with botched openings.

“Billions of dollars (are) lost in opening trials at sites where there are no patients,” Yeatman said. “If you can screen for patients ahead of time … and then not doing the site visit until you absolutely positively know there’s a patient there … you won’t have goose eggs when you open a trial. And these $100,000 site openings will disappear.”

 

Making Medicine More Precise, AccessibleAdvancing Technology

Genomic sequencing and testing technology has progressed exponentially since the first human genome draft was completed in 2001. But everyone in the field agrees that much more progress is needed to truly unlock its potential.

Thermo Fisher Scientific is working toward that end in partnerships with the federal government and pharmaceutical companies, said James Godsey, vice president of R&D for Thermo Fisher’s Clinical Next Generation Sequencing Division.

Thermo Fisher is working with the National Cancer Institute to demonstrate the usefulness of genomic testing as a new standard for guiding treatment, Godsey said. The company has a large center in Carlsbad, acquired when it purchased Life Technologies in a deal completed in 2014 for $13.6 billion. The company competes with Illumina in selling instruments for next-generation sequencing, or NGS.

“Now, the focus is shifting to actionable cancer genes, the identification of those in a very efficient manner,” Godsey said.

For Novartis and Pfizer, Thermo Fisher is developing advanced cancer tests to be used as companion diagnostics for new drugs. This is one way to increase effectiveness by selecting patients whose tumors are genetically vulnerable to specific drugs. Better targeting could also lower prices, by avoiding the use of drugs that are likely to be ineffective.

Getting medicines approved by the U.S. Food and Drug Administration should be easier when accompanied by a test, he said.

“Our goal there is to create the first multi-analyte, universal companion diagnostic NGS panel that enables that,” Godsey said. “The effort is substantial on many fronts. We have to develop the product; the software and the instrumentation, and validate that on their initial (genomic) markers.”

Once that is done, Novartis and Pfizer can simply test their new drugs or drugs from other companies on Thermo Fisher’s FDA-approved 52-gene panel, which quickly detects the presence of thousands of genetic variants associated with solid tumors.

“The time to market approval, the cost, the risk, all is driven down dramatically,” Godsey said. “We think this is central to the success of precision medicine.”

To read this entire article, published online by The San Diego Union-Tribune, please click here.

Insurers’ Fine Print May Exclude Health Care Important To Women

Insurers' Fine Print May Exclude Health Care Important To WomenBuried in the fine print of many marketplace health plan documents is language that allows them to refuse to cover a range of services that are used more often by women, a study finds.

It’s unclear if these exclusions have prevented patients from getting needed treatments. An insurance industry representative says patients are generally able to get care if it’s appropriate for them. Yet some women with a family history of hereditary breast and ovarian cancer, for instance, may have gaps in care because of the exclusions.

More broadly, advocates say, the report suggests coverage issues that may still need to be addressed, despite significant improvements in coverage of women’s health needs following passage of the Affordable Care Act.

The study by researchers at the National Women’s Law Center, an advocacy group based in Washington, D.C., examined exclusions in marketplace plans offered by 109 insurers in 16 states in 2014 and 2015.

The health law requires insurers to explain whether they cover 13 services, including acupuncture, bariatric surgery and infertility treatment, in a plan’s easy-to-read general summary of benefits. But other services that aren’t required to be listed there may also be excluded. And those exclusions may be hard to find in the more detailed plan coverage materials, which can be quite technical and run dozens of pages.

The researchers reviewed plans’ detailed documents and identified six types of excluded services that could have a disproportionate impact on women’s health care, although many of them also are used by men. The excluded services included:

  • Treatment for conditions that result from noncovered services, such as an infection following cosmetic surgery. They were excluded by 42 percent of plans.
  • Maintenance therapy for a chronic disease or other care that prevents regression of a stable condition (27 percent of plans).
  • Genetic testing, except as required by law (15 percent).
  • Fetal reduction surgery, which is sometimes recommended when a woman is carrying multiple fetuses in order to protect the woman’s health or improve the odds of a successful pregnancy (14 percent).
  • Treatment for self-inflicted conditions, such as a suicide attempt (11 percent).
  • Preventive services not required by law (10 percent).

“We wanted to highlight issues that would have a particular impact on women as well as show how broad some of the exclusions are,” says Dania Palanker, who co-authored the study and is now an assistant research professor at Georgetown University’s Center on Health Insurance Reforms.

It’s not uncommon for women who have a family history of breast or ovarian cancer to run into this type of roadblock when they need genetic testing or preventive services, says Lisa Schlager, vice president of community affairs and public policy at Force, an advocacy group for people affected by hereditary breast, ovarian and related cancers.

The Affordable Care Act requires insurers to cover services that are recommended by the U.S. Preventive Services Task Force, an independent panel of medical experts, without requiring consumers to pay anything out of pocket. The task force recommends that women with a family history of breast or ovarian cancers receive genetic counseling and, if necessary, testing for a mutation in the BRCA1 or BRCA2 genes that are known to increase the risk of developing those cancers.

However, insurers aren’t required to cover testing for the 40 or so other genetic mutations that are also recognized as increasing women’s risk of breast or ovarian cancer, Schlager says, and many don’t do so.

If a woman does test positive for a BRCA mutation, insurers may not cover earlier or more frequent screening or other preventive care she may need, Schlager says.

“We are in this strange scenario where insurers are paying for the testing and then not paying for the breast MRIs or prophylactic mastectomies,” she adds.

Clare Krusing, a spokeswoman for America’s Health Insurance Plans, a trade group, calls the report “overblown.” She says it fails to address whether treatments are safe and effective for all patients; whether other effective treatments are covered; and whether there are processes to help patients get access to excluded treatments.

“If a patient has a medically necessary reason for this care, it will likely be covered,” Krusing says.

Kirsten Sloan, senior policy director at the American Cancer Society Cancer Action Network, says people who use the society’s call center aren’t generally complaining about plan coverage exclusions. Still, coverage distinctions may be confusing for patients, Sloan says, and highlight the need for better transparency in communicating coverage information.

To read this full article on NPR, please click here.

Tiny 3D Models May Yield Big Insights Into Ovarian Cancer

Tiny 3D Models May Yield Big Insights Into Ovarian CancerWith a unique approach that draws on 3-D printing technologies, a team of University of Wisconsin-Madison researchers is developing new tools for understanding how ovarian cancer develops in women.About 1.5 percent of American women will be diagnosed with ovarian cancer, but most of them will not be diagnosed until late in the disease’s progression — after the cancer has spread to other parts of the body. This is reflected in the grim outlook for most women: The five-year survival rate for ovarian cancer is about 25 percent.

Paul Campagnola, a professor of biomedical engineering and medical physics at UW-Madison, leads a group of researchers aiming to improve that outlook by understanding how ovarian cancer cells interact with nearby body tissue, and by developing new tools for imaging and detecting the disease. With a $2 million grant from the National Institutes of Health, they will use technology they’ve developed on the UW-Madison campus to develop images of tissues from surgical patients. The first target is collagen, a common protein that gives much of the body structure by holding bones, ligaments and muscles together.

“In most cancers, including ovarian, there are large changes in the collagen structure that goes along with the disease,” Campagnola says. “It might happen first. It might be later. It’s actually not known.”

Campagnola and his colleagues, including Kevin Eliceiri, director of UW-Madison’s Laboratory for Optical and Computational Instrumentation, and Manish Patankar, associate professor of obstetrics and gynecology, hope to eliminate that unknown by printing tiny, 3-D models of the collagen samples.

The models will be biomimetic — synthetic, but mimicking biological materials, as Velcro mimics the burs of a plant — and extremely small. Because, after seeding the models with ovarian cancer cells, the researchers will implant them into mice.

Why not simply inject the mice with cancer cells and skip the painstaking imaging and 3-D printing process? Mice don’t get ovarian cancer — a partial answer for why we still don’t understand ovarian cancer as well as many other cancers.

“The current way that people study ovarian cancer in a mouse is very poor,” Campagnola explains. “They just take human cell lines and then inject them into a mouse. Then some of them will form into a tumor, but most do not.”

By implanting a 3-D tissue model seeded with ovarian cancer into mice, Campagnola hopes to mimic more closely the conditions of metastatic ovarian cancer in humans.

“What’s different is our tissues will already be 3-D structured,” Campagnola says. “One problem when people study cancer sometimes is that they put cells in a dish. Cells in a dish don’t act like cells in tissue. So we’re trying to give them the tissue structure that cancer cells would have in a native environment.”

From there, they’ll study how the implanted tumors grow inside the mice, and hopefully begin to learn more about the cues and processes involved in the disease’s progression and spread.

It’s an approach that no one has ever attempted, one that will also help improve the way doctors make images of ovaries inside the body.

“It’s an integrated approach to improving our imaging capabilities, but then also using our imaging capabilities to make these models so we can study the biology,” Campagnola says.

Ultimately, the team’s long-term goal is to improve screening, diagnosis and treatment of ovarian cancer. One of the most effective ways to improve the outlook for women with ovarian cancer is to develop a straightforward method for screening women at higher risk for the disease. Women with a mutation in a gene called BRCA — a mutation also implicated in a higher risk for breast cancer — have a 40 percent chance of developing ovarian cancer in their lifetime.

“Those are the women we really want to follow,” Campagnola says. “You could imagine — we’re a long way off from this — screening those women every few years with a minimally invasive device through a laparoscope or through the fallopian tubes.”

But to get to that point, Campagnola says, researchers need to know a lot more about how ovarian cancer works.

“You have to know what you’re looking for,” he says. “That’s why we have all this more basic work to do to get to that point. That’s why we need better imaging tools and we need better models to understand the biology of the disease.”

To read this entire article on ScienceDaily, please click here.

Protein Discovery May Lead to Superior Ovarian Cancer Detection

Researchers have discovered a protein that may help detect ovarian cancer early, along with an enzyme vital to the growth and spread of the disease, with both findings providing a potential target for new treatments.

The key to beating ovarian cancer is early detection and treatment; if the cancer is found early, it typically responds well to chemotherapy. However, once it metastasizes it becomes chemo-resistant, and extremely difficult to kill.

“We need to save the lives of more women by making ovarian cancer treatment more effective,” said Katherine Taylor, chief executive at Ovarian Cancer Action. “There has been little progress in ovarian cancer treatment in the past 30 years so these findings are promising, and have provided 2 areas of focus for scientists working on ovarian cancer. Early detection and effective treatment are vital, and these discoveries will hopefully bring us closer to both.”

In a study published in EBioMedicine, researchers found that individuals with ovarian cancer, and those with inherited mutations in BRCA1 and BRCA2 genes, had higher levels of the protein SOX2 present in their fallopian tubes.

“Ovarian cancer can be undetectable for up to 4 years and only a third of people with the cancer get an early diagnosis,” said researcher Professor Ahmed Ahmed. “A test for SOX2 could not only help detect cancers early but in some cases would enable us to detect a tumor before it becomes cancerous. Early treatment hugely improves the odds for patients, so early detection is essential. However, there is still a lot of work to be done because detecting SOX2 in the fallopian tubes is not an early task.”

During a second study published in Cancer Cell, researchers identified an enzyme responsible for enabling ovarian cancer to metastasize. Once the cancer starts to spread, it will typically do so in the omentum, which is an apron of fatty tissue that covers the small intestine, and is rich in adipocytes.

In prior research, the free fatty acids produced by these cells increase the spread of cancer. However, the results of the current study showed that ovarian cancer was only able to proliferate in the presence of the enzyme SIK2, which plays a role in fat burning to produce energy that cancer cells need to survive in the omentum.

“We continued this study of SIK2 and found that levels of the enzyme were higher in secondary tumors in the omentum than in the related primary tumors in the ovaries,” Ahmed said.

Following a series of experiments, researchers were able to confirm that SIK2 not only played a key role in the growth of ovarian tumors, but also in the metastasis that spreads them to the omentum, where they become much more lethal.

“SIK2 is an important target for future treatments because it provides cancer cells with energy and also drives their increase in number,” Ahmed said. “Our experiments showed that suppressing SIK2 disrupted these pathways, which in the human body would reduce the possibility of cancer cells spreading and coming back.”

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Liquid Biopsies Improve Ovarian Cancer Recurrence Detection

Liquid Biopsies Improve Ovarian Cancer Recurrence DetectionLiquid biopsies can detect ovarian cancer recurrence long before the tumor reappears, a new study found.

The study, published in Scientific Reports, included 10 patients with advanced stages of ovarian cancer who had their blood drawn before and after surgery. Researchers used mate-pair sequencing to compare DNA from the liquid blood biopsies to DNA tissue samples taken from the tumor.

“In this study, the blood drawn before and after surgery and the surgical tissue was used to identify DNA fragments with abnormal junctions that can only be seen in this patient’s tumor DNA,” said researcher George Vasmatzis, PhD. “Next generation mate-pair sequencing was used to identify specific DNA changes of the tumor to create an individualized monitoring panel for liquid biopsy. This allows us to shape treatment to the individual patient rather than using a standard treatment that may not work for everyone.”

The results of the study revealed that when post-surgery DNA matched the tumor, patients had recurrence of ovarian cancer later on. When the post-surgery DNA did not match the tumor DNA, patients were found to be in remission.

In 2015, more than 21,000 women in the United States were diagnosed with ovarian cancer, and 14,000 died from the disease, the study cited. Often, the tumor cannot be detected until the late stages of the disease, causing ovarian cancer to have one of the highest death rates of all gynecological cancers.

Although most patients go into remission after the initial treatment, the tumor ends up returning 75% of the time, and typically does not respond to chemotherapy.

“With liquid biopsies, we don’t have to wait for tumor growth to get a DNA sample,” Vasmatzis said. “This important discovery makes it possible for us (to) detect recurrence of the disease earlier than other diagnostic methods. We can repeat liquid biopsies to monitor the progression of the cancer. That gives hope of a better treatment plan over time.”

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