NFCR Writer David Perry, Author at NFCR

NFCR Writer David Perry

Man Up: June Is Men’s Health Month

“Even in the face of better, more accessible detection and prevention programs, we need men to recognize and adopt healthier lifestyles,” said President Bill Clinton when he proclaimed Men’s Health Week over 20 years ago. “No health care policy can replace the benefits that American men would reap from this change.”

But men’s health is tricky. From a very early age, men are conditioned to “man up” and “stick it out” in any number of situations, health-related and otherwise. The aches and pains and lumps and bumps that may actually be the first signs of a medical emergency are often ignored or regarded as something to soldier through. Because it will all go away eventually, right?

“Since childhood, boys have been told ‘big boys don’t cry,’ so men tend to put feelings aside and not express themselves,” says advocate Ana Fadich. “That can lead to several health problems.”

However, as vice president of the Men’s Health Network, Fadich goes well beyond simple advocacy. June is Men’s Health Month, and Men’s Health Week runs from the 11th until Father’s Day on the 17th. For Fadich and her staff, it’s crunch-time. From Twitter chats to sports events, Fadich aims to inform men in all the places where they “live, work, play, and pray” that they are not invulnerable, and that for the sake of their families, for whom men often are the prime income-earner, to take the initiative to maintain their own good health. This includes a screen for a number of cancers, some of which men might not even know about and others that are uncomfortable for men to even think about.

  • Testicular cancer, for instance, is a young man’s disease, striking as early as 15.
  • Skin cancer is a particular concern because men tend to equate sunscreen with frou-frou beauty products and so forgo it all together.
  • While leaps and bounds have been made with prostate cancer awareness, the prospect of a rectal exam still keeps many men away from the doctor’s office (a simple blood test is all it takes for a correct diagnosis).
  • That discomfiture carries over to colorectal cancer; the thought of a colonoscopy can be simply too much to bear, even if the necessity is acknowledged.
  • The irony is that all these cancers have several obvious symptoms in their early stages when they are most easily and successfully treated, but are either not recognized or not diagnosed in time.

“It is very important for men to do their own self-exams,” says Fadich. “With testicular cancer, you do it in the shower. Feel around and test if there are any lumps, and if there are, go to your doctor and talk about it. Young boys don’t even know the difference between testicles, and say, the prostate. They know the names, and I think it’s great in media you are able to hear about the different ways people address them. But we need more men that are out there to talk about these health issues and get guys to actually do these tests themselves.

“We were seeing that there were a lot of women’s health movements, a lot of programs geared toward women getting their mammograms, making sure they were getting proper nutrition, getting pap smears,” she continues. “And men just didn’t seem to have that, and men were perfectly fine with it because it meant they didn’t have to go to the doctor.”

But men do have to go to the doctor. It was because of that urgency that Men’s Health Week was established in 1994. Far from being restricted to just cancer, it is a time when all the medical conditions affecting men should be on the table and up for discussion, however uncomfortable the discussion may be.

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References:

  • Clinton, William J. Proclamation 6700 — National Men’s Health Week, 1994. Washington, D.C., 1994.
  • Fadich, Ana. “Men’s Health Week: Interview with Ana Fadich,” interview by David Perry. nfcr.org. May, 2018.

 

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Immunotherapy: Where We’re Headed

It is the “new territory” of oncology: Getting the immune system to successfully fight a standing cancer. No other biological system within our bodies is more suited, adept or evolved to such a purpose. Indeed, our immune system is remarkably successful in spotting and destroying the tiny genetic mutations from which a tumor arises.

Except when it isn’t.

The ability of cancer, any cancer, to go unnoticed by the body is one trait which what makes it so formidable and unique a disease type. Unfortunately, the goal of totally reorienting the immune system in any way is still unrealized. But that is not to say science has not come very close. Indeed, it is getting closer.

June is Cancer Immunotherapy Awareness Month. And the National Foundation for Cancer Research (NFCR) is excited to be offering this blog post—a deeper dive into this equally exciting tumor treatment category, still only in its adolescence.

Let’s look at differing elements of immunotherapy.   

Monoclonal Antibodies

A diverse group, monoclonal antibodies, also known as MABs, work by attaching themselves to cancer cells, thereby making it easier for the patient’s body to recognize them as hostile. One type of MABs, called checkpoint inhibitors, block the proteins cancer produces which, otherwise, “inhibit” a desired immune response. They are already used to treat some melanomas and lung cancers. Still other MABs prevent cancer cells from dividing.

Cytokines

Perhaps the most famous cytokine is interferon. At its most basic, interferons are naturally occurring proteins made by the cells of the immune system. While they do not directly kill cancerous cells, interferons do modulate how the immune system responds to a threat, cancer or otherwise. However, scientists have since manufactured interferons using recombinant DNA as cancer therapies, such as interferon alfa-2a (also known as Roferon-A), which is used to treat hairy cell leukemia, HIV/AIDS-related Kaposi sarcoma, and chronic myelogenous leukemia. Another type of cytokine is aldesleukin, used most often in attacking kidney cancer.

Cancer Vaccines

A relatively new idea, a cancer vaccine works along the same lines as vaccines for smallpox or the flu, the idea behind a cancer vaccine is to “fool” a patient’s immune system into thinking it is suffering a malignancy—even though, in the case of “preventive” vaccines it may not be, versus “therapeutic” vaccines, where it is. The result is the creation of antibodies capable of staving off cancer before it has a chance to take root, or to stop a cancer already underway, or to destroy any cancer cells remaining after another form of treatment.

Adoptive Cell Transfers

Still very new, the most promising adoptive cell transfer technology, CAR T-cell therapy, is a process by which a patient’s T-cells, also called “killer” T-cells, are harvested and genetically engineered in order to better seek and destroy cancer that has so far eluded detection. These man-made T-cells can persist in the body for years, guarding against cancer’s return.

Oncolytic Virus Therapy

The idea of injecting a virus into an already sick patient can be unsettling, but this type of immunotherapy is already being used to treat melanoma, the most virulent form of skin cancer. A genetically modified virus is put into a tumor, where it invades the constituent cells and begins to make copies of itself, causing the infected cell to eventually burst and die. As those cells die, they release antigens that a patient’s immune system recognizes and then creates antibodies targeting all cells with those same antigens. The virus does not harm the patient.

BCG

Short for Bacillus Calmette-Guérin, this technology is currently used to treat bladder cancer. Similar in idea to oncolytic virus therapy, this technology uses a bacterium instead of a virus. A weakened form of the same bacteria that causes tuberculosis is inserted into the bladder, causing an immune response against the cancer cells. This process is being studied for other cancers as well.

All these therapies are administered in familiar ways, such as orally, topically, intravenously, or via the bladder, a process called intravesical. As a field, immunotherapy still qualifies as an emerging science, trailing well behind the conventional cancer treatments of surgery, chemotherapy and radiation. At the same time, several immunotherapies have moved out of clinical trials and are open to the public, while other immunotherapies are already in clinical trials.

Multiple NFCR-funded fellows are performing research on the cutting edge of the immunotherapy categories introduced above. For example, Wayne Marasco, M.D., Ph.D., is recognized as a world-leader in the field of monoclonal antibodies, and his efforts hold great promise for the treatment of renal cell carcinoma, the most common type of kidney cancer, and other tumor types. Cytokine and viral cancer therapies both are associated with few scientists whose laboratories offer as much promise as do those of Paul Fisher, M.Ph., Ph.D. Other recent examples include CAR-T expert, Laurence Cooper, M.D., Ph.D.

This is the field of immunotherapy. And with our understanding of genetics and genetic engineering growing in leaps and bounds every day, it is a field generating tremendous hope for cancer treatments. With justification—and NFCR support!  

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References:

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Douglas Lowy & John Schiller: An Ounce of Prevention

When Douglas R. Lowy, M.D., and John T. Schiller, Ph.D., receive the 2018 Albert Szent-Györgyi Prize for Cancer Research, it will set a precedent for the honor itself. By creating an effective vaccine for the human papillomavirus (HPV), cause of practically all cervical tumors, Lowy and Schiller forged a means to virtually eliminate at least one kind of cancer. And for the first time in the history of the Prize, the award goes not to the discoverer of a particular mechanism of cancer or a new drug target, but to the inventors of a means to prevent tumors altogether.

“HPV is responsible for more than 275,000 deaths per year,” says Lowy. “The vaccine has the potential to drastically reduce that number.”

Worth a Pound (and Dollar) of Cure

He is not spinning the vaccine’s potential impact. Now on the market as Gardasil and Gardasil 9 from the U.S. manufacturer Merck and as Cervarix from the U.K.’s GlaxoSmithKline, its work is cut out for it. There are more than 100 types of HPV, of which at least 13 are cancer-causing. And while HPV is mostly linked to cervical cancer, the virus too causes approximately 95% of anal cancers, 70% of oropharyngeal cancers, 65% of vaginal cancers, 50% of vulvar cancers and 35% of penile cancers. Indeed, high-risk HPV types cause approximately 5% of all cancers worldwide.

It is perhaps ironic that neither Lowy nor Schiller went into oncology with a vaccine particularly in mind. Cancer ran in Lowy’s family and that personal experience set him to cancer research from a clinical standpoint. On the other hand, Schiller is a microbiologist and molecular biologist by training.

“And when I first started, it was just before there was any real inkling that HPV caused cervical cancer,” says Schiller, recalling the early days of his and Lowy’s research in 1983.

It was a lecture by Harald zur Hausen, who first noticed HPV’s role in cervical cancer and would later win the Nobel Prize for his work that rerouted the two.

“I came strictly to study this model system of how to make normal cells into cancer cells by putting a virus into it,” Schiller continues. “And suddenly, I was going from just studying a model system of trying to understand what cancer is, to studying a group of viruses that looked like it was actually going to be a substantial cause of cancer. But we were still studying how they caused cancer. It wasn’t until about 10 years later that we started to work on the vaccine.”

Simply put, the HPV vaccine works by fooling the patient’s immune system into thinking there is an infection so as to make antibodies. The vaccines target the HPV L1 major capsid protein, which can assemble to form virus-like particles morphologically resembling native virions, to generate an immune response strong enough to overwhelm HPV. Interestingly enough, HPV LI is not part of the virus itself, but rather forms the shell surrounding the virus. Nevertheless, it provides the correct immunological response that is able to prevent an HPV infection, and the changes that ultimately lead to cancer from it.

Schiller says that while it is relatively easy enough to describe, the arc of the vaccine, from research to finished product, took 15 years to complete. He is acutely aware of the time span, as his daughter was born around the time he and Lowy began their work!

A Unique and Inspiring Partnership

And as Lowy and Schiller emphasize, and the Szent-Györgyi Committee recognizes, the HPV vaccine is the result of teamwork. Lowy and Schiller exemplify the idea. Their collaboration spans decades. When asked about their syzygy, the two let the superlatives fly.

“My research is far better as a result of working with John than it would have been working without him,” says Lowy.

Doug and I have had this wonderful collaboration for 30 years,” says Schiller. “It’s relatively unusual that people can continuously work together for that amount of time.”

Both are equally unanimous in their grace winning the Szent-Györgyi Prize.

“It’s incredibly gratifying to receive this kind of recognition from such an outstanding group of peers,” Schiller says. “The people who made this selection are the who’s-who of cancer research.”

Adds Lowy, “I was amazed. I think of the Szent-Györgyi Prize as certainly one of the top prizes in cancer research, but I also think about it being a prize usually either for fundamental discoveries or for cancer treatment, and to highlight an advance in cancer prevention was really something I never expected.”

Groundless Challenges Unfortunately Remain

But both doctors acknowledge that even with such accolades, their work continues—and certainly not always along predictable lines. A bitter paradox is that just because there is a vaccine does not mean people will, or can, take it. In poor countries where HPV-related cancers are rampant, the vaccine is often cost-prohibitive. In rich countries, HPV, like HIV/AIDS, carries a social stigma of being a sexually transmitted disease (STD). Schiller laments that parents can be unwilling to vaccinate their children for an STD (or vaccinate at all), and also notes healthcare provider hesitancy is not helping either. The best thing for doctors to do, he advises, is to discreetly downplay the vaccine.

“Just say that ‘it’s time for your meningococcal, HPV, and DPT; roll up your sleeve’ and they get much better uptake rates,” Schiller says. “Physicians think they have to talk about HPV and point out that it’s sexually-transmitted, but it really isn’t necessary. All you have to say is that it is time to take these vaccines.”

The Szent-Györgyi Prize for Progress in Cancer Research was established in 2006 by the National Foundation for Cancer Research (NFCR) in honor of its co-founder, Albert Szent-Györgyi, M.D., Ph.D., recipient of the 1937 Nobel Prize for Physiology and Medicine. It recognizes and honors scientists who have made seminal discoveries that have resulted in, or led toward significant contributions to, cancer prevention, diagnosis and treatment with a high impact of saving people’s lives.

Colleagues at the U.S. National Cancer Institute’s Laboratory of Cellular Oncology since 1983, Lowy and Schiller have co-authored more than 150 publications related to the molecular biology, immunology, and epidemiology of the papilloma virus. Their accomplishments have been recognized by such other awards beyond the Albert Szent-Györgyi Prize for Progress in Cancer Research as the Albert Sabin Gold Medal Award (2011), the PhRMA Research and Hope Award (2013), the National Medal of Technology and Innovation from President Barack Obama (2014) and the Lasker-DeBakey Clinical Medical Research Award (2017).

The gentlemen will be honored at an award ceremony held Saturday, May 5th, in Washington, D.C.

References:

NFCR thanks Doctors Lowy and Schiller for their Spring 2018 interviews

 

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Hail, Bounteous May!

May is Cancer Research Awareness Month, a time highlighting the vital role of study and experimentation in the quest for cancer cures. As such, it is a particularly special month for the National Foundation for Cancer Research (NFCR). If fact, our Svent-Györgyi Prize for Progress in Cancer Research ceremony, NFCR’s flagship annual public event, will again this year fall accordingly—this coming Saturday, May 5th

It is not just the scientists and physicians that are to be honored. Patients, survivors, supporters, and trial subjects are too recognized for their contributions to battling a disease that is anything but straightforward to cure. Indeed, funding and awareness remain as important now as they ever were.

“The National Foundation for Cancer Research is focusing on the connections between basic and clinical research—giving more reasons for progress being made against cancer,” declared NFCR CEO Franklin Salisbury, Jr. “Bringing smarter, more effective treatments into the clinic, more cures can be delivered and patient’s lives saved.”

Part of the role Cancer Research Awareness Month serves is to emphasize the need for adequate funding for a disease that still kills more people than are cured of it. Dr. Margaret Cuomo, in her book A World Without Cancer, estimates that while there has been a drop in the cancer death rate, it is only by 1% every year, and only since 1990.

“Still, that’s hardly cause for celebration,” she writes. “Cancer’s role in one out of every four deaths in this country remains a haunting statistic.”

Distinguishing itself in the cancer sector by emphasizing long-term, transformative research often overlooked by other major funding sources, NFCR has delivered more than $350 million in funding to public education and cancer research leading to several important, life-saving discoveries with the help of more than 5.3 million individual donors over the last 45 years.

The Foundation channels its resources into very specific mechanisms of cancer’s biology, such as angiogenesis (the formation of blood vessels), along with such dynamic fields as personalized and targeted therapies, therapeutic antibody engineering and genomics. And yet our organization prides itself on being so much more than only a source of funds.

For example, the NFCR plays a leading role in supporting projects including GBM AGILE, a global medical and scientific collaborative effort representing the first disease-specific adaptive clinical trial platform for glioblastoma multiforme (GBM), a dreaded brain cancer. The international effort is designed specifically to capitalize on a growing knowledge base, incorporate novel clinical trial advances and leverage emerging capabilities to undertake more innovative and complex trial protocols.

Equally important, and in what is a strong undercurrent to Cancer Research Awareness Month, the NFCR aims to help bring developments to patients in as timely a manner as possible. The GBM AGILE effort is just one example of how we are dedicated to shortening the time between a laboratory discovery, which takes place in what can be an insular environment, to new treatments in clinics and hospitals.

“There is a deafening silence about available cancer treatments today that needs to be addressed if we hope to translate the breakthroughs in research to patients at their bedsides,” Franklin explains.

“It’s going to be research that cures cancer,” he continues. “As a catalyst for the kinds of ‘disruptive innovations’ that are accelerating the development of successful new approaches to treating cancer, all types of cancer, NFCR is prioritizing the connections between basic cancer research and translating discoveries being made in the laboratory into new treatments.”

And, if anything is, this is worth recognizing and honoring!

One of NFCR’s generous partners has agreed to help us fund vital cancer research by matching every dollar you give to the Matching Gift Challenge, up to $130,000!

Join the Challenge, Double Your Impact!

 

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Michael Hall: TOR de Force

Dr. Miachel Hall

Dr. Michael Hall’s speech about his work discovering TOR (target of rapamycin) at NFCR’s 2017 Szent-Györgyi Prize Ceremony

The discovery of rapamycin in 1972 did not create major waves in the oncology community. But in 1989, Michael N. Hall, Ph.D., took a second look, screening yeast cells for rapamycin resistance. That led to the discovery of TOR, or “Target Of Rapamycin,” and one of the most profound paradigm shifts in medical science.

“TOR is a highly conserved, nutrient-activated protein kinase,” Hall explains. “More importantly, it is a central controller of cell growth.”

The Benefits of Regulation!

And not just cell growth; this kinase (a specialized enzyme), also called mTOR, is in fact very busy in the body. TOR is linked to cell proliferation, motility, protein synthesis, cell survival and orderly death, and takes a role in the first steps of gene expression. The enzyme has a hand in insulin activation and control of the actin cytoskeleton. Perhaps because it has so many functions, it is understandable that so many things can go wrong when TOR malfunctions. Cancer, diabetes, cardiovascular disease and obesity all have causes linked to the misregulation of TOR. Of all those maladies, highest on Hall’s list is the relationship between cancer and TOR.

“With the realization that TOR controls growth and metabolism, the importance of targeting… mTOR pathways increased,” says Hall. “The state of cancer research was quite advanced at the time we discovered TOR. What was not advanced was our understanding of cell growth control and thus how this could be targeted to treat cancer.”

He explains that when that this pathway is activated, it contributes to tumor growth in 70 percent of all cancers. With TOR also came the notion of targeting cellular metabolism, cancer cell metabolism in particular. The idea of targeting metabolism was not new with the discovery of TOR, but the discovery of TOR put this notion on firmer ground, and provided a new, viable target for drug researchers.

A Modest Luminary

Therefore, it should come as little surprise that Hall is the 2017 recipient of the prestigious Szent-Györgyi Prize for Progress in Cancer Research. Established in honor of National Foundation for Cancer Research co-founder Dr. Albert Szent-Györgyi, Ph.D. (who received the 1937 Nobel Prize for his study of vitamin C and cell respiration), the yearly award is a symbol of the organization’s enduring commitment to uphold Dr. Szent-Györgyi’s vision of curing cancer through innovation and collaboration. The Prize, bestowed to those scientists who made an original discovery or breakthrough, serves to highlight the essential role basic research plays in understanding cancer.

“The award of the 2017 Szent-Györgyi Prize to Dr. Hall is a wonderful recognition of his breakthrough discovery of TOR which has made possible many of today’s advanced anti–cancer therapies,” proclaimed Dr. Sujuan Ba, NFCR President. “His pioneering research is a great example of how laboratory research at the fundamental stage can impact cancer treatment and care for many patients around the world.”

But Hall demurs, saying only, “I am extremely honored, particularly when considering the previous laureates.”

The humility is disarming, and (as those who know him well confirm), genuine. But the man is a veritable prize-magnet: the Cloëtta Prize for Biomedical Research (2003), Louis-Jeantet Prize for Medicine (2009), Marcel Benoist Prize for Humanities or Science (2012), Breakthrough Prize in Life Sciences (2014), and the Canada Gairdner International Award (2014) all adorn his résumé, as do others. Hall is also a member of the U.S. National Academy of Sciences, and Professor of Biochemistry at Biozentrum of the University of Basel, Switzerland, for those counting.  

Pathways to Success

The fruits of Hall’s discovery are plain. Today, TOR inhibitors are used to treat kidney, breast, brain and pancreatic cancers, and numerous clinical trials are currently underway testing TOR inhibitors in the treatments of many types of cancer. Thousands of lives have been saved. But, knowing full well that nothing wilts faster than the laurels you rest on, Hall continues his work unabated, prizes or not.

“There are many new treatment strategies to be identified and exploited,” he says. “Among these are the needs to identify pathways that mediate evasive resistance to targeted cancer drugs. Once such secondary pathways are identified, they can also be blocked to prevent resistance.”

The 2018 Szent-Györgyi Prize Ceremony takes place Saturday, May 5th, in Washington, DC. Following tradition, Hall, as last year’s winner, will present the award to this year’s winners, Douglas R. Lowy, M.D., and John T. Schiller, Ph.D. for their development of vaccines for the human papillomavirus.


References:

NFCR thanks Dr. Hall for his Spring 2018 interview

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Medical Coalition Led Largely by NFCR Unites to Battle Glioblastoma

Medical knowledge of glioblastoma multiforme (GBM), the deadliest form of brain cancer, has grown exponentially, but has not resulted in marked improvements in treatment for patients. Addressing this is GBM AGILE (GBM Adaptive Global Innovative Learning Environment), a global medical and scientific coalition that is the first platform trial for GBM.

The ambitious initiative is introduced in detail in a February 2018 marker paper published by the American Association for Cancer Research journal, Clinical Cancer Research. GBM AGILE is designed to translate the growing knowledge base about the disease into effective clinical trials of candidate drug products and combinations, far better incorporating novel clinical innovations and global capabilities into complex trial protocols than is currently the case. The goal: Nothing less than new and better GBM treatments.

The National Foundation for Cancer Research (NFCR) is playing a leading role. In addition to financial and coalition building support, among the decision makers guiding the endeavor are the following, each a member of the Executive Committee to the Global Coalition for Adaptive Research (GCAR), the newly created formal management body for GBM AGILE:

  • Dr. Sujuan Ba, NFCR President and a member of GCAR’s Board of Directors
  • Dr. Michael Wang, NFCR Chief Strategy Officer
  • Dr. Webster Cavenee, NFCR’s Scientific Advisory Board chairman and GCAR Chief Scientific Officer
  •  Dr. W.K. Alfred Yung, a longtime NFCR Fellow and GCAR Chief International Development Officer

I know I speak for all of the patient advocacy groups when I say that the commitment we have seen from the international GBM research communities to unite different disciplines and break down barriers for the benefit of GBM patients is inspiring to all of us,” said Dr. Ba.

We have to do something more—something different—something that brings the best science and innovative clinical trials together to identify therapies that work,” adds Dr. Mitchell Berger, a GBM AGILE co-investigator and Chief of Neurosurgery at the University of California at San Francisco. “GBM AGILE is the best path to achieve those goals than I have seen for decades.

With roots tracing to 2015, GBM AGILE is a two-stage, multi-arm, platform trial comprised of figures with glioblastoma multiforme basic and clinical research expertise identifying the most promising therapies and biomarkers for the dreaded disease. Coalition doctors will then use obtained knowledge to inform the design of a new-generation adaptive trial that reconfigures as new patients enter—“learning” which candidate drugs and cocktails thereof present the greatest likelihood of success.

By including patients with both newly diagnosed and recurrent tumors and accounting for their presentation in a statistical model, the trial design will facilitate integration of knowledge that might have otherwise been disparate. Importantly, although GBM AGILE is designed to identify effective therapies and develop biomarkers for GBM, the overall process and philosophy could also be adapted for other rare cancers and diseases. When the GBM AGILE initiative began taking form, there were no virtually no biomarkers that could be employed to drive drug development and guide treatment. As a result, GBM patients have not benefited from the advances known as precision medicine.

An experimental arm (a model of treatment that includes the patient) that performs sufficiently well during its initial stage will “graduate.” Graduation signals a seamless move into the arm’s confirmatory stage. Doctors expect many arms to be added and removed as GBM AGILE progresses. An arm can be added to the trial at any time after it is approved by relevant GBM AGILE committees, provided the patient accrual rate is sufficient.

The GBM AGILE trial design offers the opportunity to accelerate delivery of improved therapies to trial participants, whereas the broadly defined eligibility criteria will leverage information learned from more patients. The seamless inferential design means that highly effective treatment arms proceed rapidly through the trial, enabling faster registration, regulatory review and adoption for routine clinical care. While even unsuccessful treatments will still be mined for information concerning potential contributions.

Thanks to the deep molecular characterization of GBM, we are beginning to get a better picture of the genes and pathways that are altered in GBM, so there is finally an opportunity to identify real biomarkers and conduct a ‘smart’ trial like GBM AGILE,” said Dr. Yung.

There were an estimated 22,810 cases of primary malignant brain tumors in United States in 2014, of which GBM is the most common type. Median survival for adults with the anaplastic astrocytoma form of GBM is about two to three years; for more aggressive gliomastomas treated with temosolamide and radiation (the standard protocol), the median survival rate is 14.6 months while the two-year survival rate is 30%. Child patients fair slightly better, with the five-year survival rate at around 25%.

 

References:

  • Brian M. Alexander, Sujuan Ba, et al. Adaptive Global Innovative Learning Environment for Glioblastoma: GBM AGILE. (February 2018) Clinical Cancer Research. DOI: 10.1158/1078-0432.CCR-17-0764

 

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New Test Developed for Pre-Cancerous Barrett’s Esophagus

In recognition of Esophageal Cancer Awareness Month, this National Foundation for Cancer Research post offers a look at a significant diagnostic advancement for a risk factor associated with the terrible disease.

A new test for Barrett’s esophagus, a precancerous forerunner of the much deadlier esophageal adenocarcinoma, is in clinical trials and may replace, or at least strongly augment, the standing procedure of endoscopy. Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett’s esophagus (BE) that offers promise for preventing deaths from esophageal adenocarcinoma.

Esophageal adenocarcinoma, or EAC, is a highly lethal cancer with more than 80 percent mortality at five years. Early detection is key, and EAC can easily be prevented when still in the BE stage and early foci of near cancerous changes (dysplasias) are ablated. In a significant step forward, the Case Western team has developed an easy, five minute outpatient test that is more than 90 percent sensitive for detecting individuals with BE. Patients simply swallow a vitamin pill-sized balloon that swabs the esophagus, and that, after retrieval through the mouth (the “pill” is attached to a thin, silicone catheter), is tested for DNA abnormalities that the investigators discovered are diagnostic of BE. Traditional endoscopy is an expensive and invasive test that requires sedation and is thus often unsuitable as a method for wide BE screening.

“Our goal is early detection,” said Dr. Amitabh Chak, M.D., one of the developers of the pill and head of the Barrett’s Esophagus Translational Research Network BETRNet program. He points out that BE is often overlooked by patient and doctor alike because other, more common (and even more likely) conditions have the same symptoms.

“Symptoms, such as heartburn, can also be commonly seen in individuals who have acid reflux disease without BE,” he explains. “These symptoms can easily be treated by over the counter medications so people often don’t get tested for BE, particularly by an invasive test such as endoscopy. As a result, when individuals develop EAC, 95 percent of the time the presence of the prior Barrett’s esophagus was undetected and unknown. We wanted an easier, less costly test that could provide a practical way for screening and early detection of individuals with BE, who can then be followed closely to prevent development of EAC.”

In the clinical trial, patients tolerated the balloon test well, with 82 percent reporting little to no anxiety, pain, or choking, 93 percent stating they would repeat the procedure again, and 95 percent stating they would recommend the test to others. After delivery to the stomach, the small balloon was inflated by injecting air through the catheter. The inflated balloon was maneuvered to swab the lower esophagus near the stomach, the region where BE begins, and obtain a sample of the lining cells. Surface texturing on the balloon increased the effectiveness of the sampling. The balloon was then deflated through the catheter and inverted back into the capsule, thus protecting the esophagus sample from dilution or contamination. After retrieval of the capsule through the mouth, DNA was extracted from the balloon surface for testing.

The development of the balloon follows on the heels research done by the same team concerning for what DNA to test. It was previously found that two genetic biomarkers, VIM DNA methylation and CCNA1 DNA methylation, are common in BE.

“Having two accurate biomarkers increases confidence in our ability to correctly diagnose Barrett’s esophagus,” said Dr. Moinova, study first author and instructor at Case Western Reserve School of Medicine. “Taken together, our findings show that non-endoscopic balloon sampling paired with molecular tests for the methylated VIM and CCNA1 biomarkers is effective in addressing the need for simple, non-invasive, safe, and accurate Barrett’s esophagus screening.”

The research can found in the January 2018, issue of Science Translational Medicine.
 

 

References:

  • Moinova, Helen et al.  Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett’s esophagus.  (January, 2018). Science Translational Medicine. DOI: 10.1126/scitranslmed.aao5848
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Flu Virus Harnessed to Fight Pancreatic Cancer

Flu fighting cancer

Led by Dr. Gunnel Halldén of Queen Mary University in London, a team of scientists modified a common flu virus to successfully inhibit the growth of pancreatic cancer. The new technique could potentially become a promising new treatment for patients with the aggressive disease, and could be combined with existing chemotherapy to improve chances of survival. This is the first time that pancreatic cancers were targeted in such a manner.

“The new virus specifically infects and kills pancreatic cancer cells, causing few side effects in nearby healthy tissue,” says first author Dr. Stella Man. “Not only is our targeting strategy both selective and effective, but we have now further engineered the virus so that it can be delivered in the blood stream to reach cancer cells that have spread throughout the body.”

She continues: “If we manage to confirm these results in human clinical trials, then this may become a promising new treatment for pancreatic cancer patients, and could be combined with existing chemotherapy drugs to kill persevering cancer cells.”

Pancreatic is one of the deadliest cancers. The disease is particularly aggressive and has the lowest survival rate of all cancers, fewer than five percent of patients diagnosed survive for five years or more. Initial symptoms, such as nonspecific lower back pain, may be misdiagnosed; noticeable symptoms, such as jaundice, do not manifest until the disease has progressed into its later stages. Additionally, pancreatic cancer can also rapidly develop resistance to current therapies, and it is here that the Queen Mary study shows the most promise. To avoid drug resistance, the use of mutated viruses has emerged as a promising new strategy for attacking cancers in a more targeted way.

Halldén and her team took advantage of a unique feature of pancreatic cancer cells, the presence of a specific molecule called alpha v beta 6 (αvβ6), which is found on the surface of many pancreatic cancer cells but, crucially, not on normal cells. The team modified the common flu virus to display an additional small protein on its outer coat that recognizes and binds to αvβ6-molecules. Once the virus enters the cancer cell, the virus replicates, producing many copies of itself prior to bursting out of the cell and thereby destroying it in the process. The newly released viral copies can then bind onto neighboring cancer cells and repeat the same cycle, eventually removing the tumor mass altogether. The researchers tested the viruses on human pancreatic cancer cells, which had been grafted onto mice, and found that they inhibit cancer growth.

The concept of using modified viruses has previously shown promising results in various cancers including brain, head and neck, and prostate. The researchers say that their new virus is more specific and efficacious than previous viral versions, and has the added advantage of being able to cooperate with chemotherapy drugs that are currently used in the clinic.
The team stresses that for all its potential, the research is still in its early days, and Halldén and her team are actively searching for funding to proceed further.


References:

  • Man, Stella et al. The Novel Oncolytic Adenoviral Mutant Ad5-3Δ-A20T Retargeted to αvβ6 Integrins Efficiently Eliminates Pancreatic Cancer Cells. (Feb. 2018) Molecular Cancer Therapeutics. DOI: DOI:10.1158/1535-7163.MCT-17-0671
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Researchers Develop Antibody to Fight Colorectal Cancer

Fight Colorectal CancerPresident Bill Clinton declared March Colorectal Cancer Awareness Month in 2000, highlighting a disease that represents eight percent of all new cancers diagnosed yearly and, out of the estimated 135,430 people who developed it just last year, caused an estimated 50,260 deaths in the United States alone. As outlined in a February 2018 report, a team of researchers working at Yale University engineered an antibody that blocks the growth of colorectal cancer models. If the findings successfully move on to clinical trials in human patients, a powerful new tool in the fight against colorectal and other cancers will have been established.

The research concerns two proteins, DKK2 and Wnt. Wnt proteins, in fact, form a huge “family” responsible for signaling the developmental and biological development of cells. However, under certain conditions, scientists have come to realize that the signals coming from Wnt directly affect the development of cancer, although the mechanics of how was not understood.

“We found that this Wnt inhibitor, DKK2, which was thought to inhibit tumor formation, promoted tumors through suppression of tumor immunity,” said Dianqing Wu, senior study author and professor of pharmacology at the Yale School of Medicine. He adds, “If you inactivate, or neutralize, or blockade this inhibitor, it causes reduction of tumor formation through activation of the host’s immune system.”

Colorectal cancers are notorious for developing resistance to immunotherapies designed to trigger the patient’s own immune system into fighting tumors more aggressively, suggesting to the Yale researchers the presence of an unidentified agent acting behind the scenes, which led to the focus on DKK2. The Yale team then went about “inhibiting the inhibitor.” Wu explains how, in order to explore the role of DKK2 (short for Dickkopf-related protein 2) in cancer, researchers crossbred a mouse model of colorectal cancer with mice lacking the protein. The resulting offspring had fewer and smaller tumors.

Genetic or antibody-mediated ablation of DKK2 has been shown to potentially activate the natural killer cells of a patient’s immune system, specifically CD8+ T cells (the body’s in-built cancer killers); impede tumor progression; and enhance the effects of the PD-1 blockade, which can restore immune function within the tumor. Anti-DKK2 antibody treatment could prove a boon for medical scientists facing cancers that become resistant to immunotherapies designed to trigger the patient’s own immune system into fighting tumors more aggressively.

Another uptick is that the anti-DKK2 antibody could prove a boon for medical scientists facing other cancers that become drug-resistant. Wu and his colleagues note that in addition to colorectal cancer suppression, the antibody may also be effective in blocking the growth of certain melanomas when combined with standing immunotherapies.

The findings appear in the Nature Medicine scientific journal.


References:

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Study Better Predicts Stomach Cancer

Although stomach (AKA gastric) cancer is the third deadliest cancer in the world, claiming an estimated 10,960 lives in the United States alone in 2017, it remains one of the more difficult cancers to notice and detect. Indeed, more than two-thirds of patients are diagnosed only after the disease is at an advanced stage. A recent study out of Singapore, hailed as “landmark,” offers the potential to develop more effective screening for stomach cancer, enabling timely and better early-stage treatments.

The study focuses on a known risk factor for stomach cancer called intestinal metaplasia (IM). Patients with IM are six times more likely to develop stomach cancer than those without. The Singaporean team, composed of researchers from the National University Health System (NUHS) and the Duke University-National University of Singapore (Duke-NUS) Medical School, has used genomic technologies to better understand the pre-cancer role of IM, as well as that of Helicobacter pylori bacteria, which is also linked to the condition.

“Previous genetic studies on IM have mainly focused on patients who were already diagnosed with stomach cancer. But these are limited in their ability to predict who are likely to develop the disease and how the disease will progress,” said Professor Patrick Tan, co-lead investigator and a Duke-NUS Medical School professor. “This new study is the first to comprehensively map out the genetic changes in IM in a cohort of stomach cancer-free subjects, which helps us better predict the possible occurrence and progression of the disease.”

Although showing signs of decline in medically advanced nations, stomach cancer is notorious in medical circles for being particularly hard to detect before it enters the metastatic stage. If the cancer is diagnosed and treated before it has spread outside the stomach, the five-year survival rate is 67%. From there, the statistics become grimmer. If the cancer spreads to surrounding tissues or organs and/or the regional lymph nodes, the five-year survival rate is 31%. If the cancer spreads to a distant part of the body, the five-year survival rate plummets to five percent. Early detection is key.

A comprehensive analysis of the genetic patterns of IM can predict its subsequent progression towards stomach cancer. The genetic analysis of IM helps to identify those with a higher risk of progression to stomach cancer, adding further information to what is available by microscopic examination alone.

“Our study is the largest series of IM to be studied in detail by genetic analysis,” says Dr. Yeoh Khay Guan, co-lead investigator and Deputy Chief Executive at NUHS. “These new findings help us understand why some people have a higher risk of progression to stomach cancer, and identify those who may benefit from closer follow-up to prevent cancer or to detect it early so that it can be cured.”

Pertaining to at least one National Foundation for Cancer Research (NFCR) initiative associated with this theme of genetic research into gastric cancer, an initiative for new precision oncology treatment approaches was conducted by the Foundation in connection with its Tissue Bank Consortium in China and other scientists. A multi-disciplinary team led by NFCR scientist, Wei Zhang, Ph.D., analyzed Next Generation Sequencing data from hundreds of gastric cancer samples from the Bank, discovering defects in three cellular signaling pathways (BRCA2, Wnt and PI3-K-ERBB4). Several newly developed drugs that target these pathways have also been tested in breast and ovarian cancers, and may lead to improved treatments for patients with stomach cancer.

References:


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