Oral Cancer Foundation News Team - A

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Halving radiation therapy for HPV-related throat cancer offers fewer side effects, similar outcomes

Source: www.eurekalert.org
Author: Mayo Clinic press release

Mayo Clinic researchers have found that a 50 percent reduction in the intensity and dose of radiation therapy for patients with HPV-related throat cancer reduced side effects with no loss in survival and no decrease in cure rates. Results of a phase II study were presented today at the 59th Annual Meeting of the American Society for Radiation Oncology in San Diego by Daniel Ma, M.D. a radiation oncologist at Mayo Clinic.

“A common approach for treating HPV-related throat cancer is a combination of surgery followed by daily radiation therapy for six to 6½ weeks,” says Dr. Ma. “However, the radiation treatment can cause a high degree of side effects, including altered taste, difficulty swallowing, dry mouth, stiff neck and damage to the jaw bone.” Dr. Ma says that patients with HPV-related throat cancer tend to be young and, once treated, are likely to live a long time with possibly life-altering side effects from the standard treatment. “The goal of our trial was to see if an aggressive reduction of radiation therapy (two weeks of radiation twice daily) could maintain excellent cure rates, while significantly reducing posttreatment side effects, improving quality of life and lowering treatment costs.”

Researchers followed 80 patients with HPV-related oropharyngeal squamous cell cancer with no evidence of residual disease following surgery and a smoking history of 10 or fewer pack years. That’s the number of years smoking multiplied by the average packs of cigarettes smoked per day.

At two years following the aggressively de-escalated treatment, the rate of tumor control in the oropharynx (throat) and surrounding region was 95 percent. Of the 80 patients in the trial, only three experienced a local cancer recurrence. One patient experienced a regional cancer recurrence. Patient quality of life largely improved or did not change following treatment, except for some dry mouth.

“Patients in our trial had a very dramatic reduction in side effects, compared with standard treatment,” says Dr. Ma. “For example, no patient in our trial needed a feeding tube placed during dose-reduced treatment; whereas, close to a third of patients had feeding tubes placed with traditional radiation therapy doses on other recent clinical trials.” Dr. Ma says the reduction in side effects did not lead to any reduction in cure rate, as survival rates were similar to traditional survival rates for HPV-related throat cancer.

September, 2017|Oral Cancer News|

Norgine launches Lymphoseek in Italy

Source: www.prnewswire.co.uk
Author: press release

Norgine B.V. today announced the launch of Lymphoseek® (technetium Tc 99m tilmanocept) in Italy. Lymphoseek® is a radiopharmaceutical used for diagnostic purposes by nuclear medicine specialists and surgeons. It is specifically designed for a procedure called sentinel lymph node biopsy (SLNB) and represents a significant alternative to the current method of identifying sentinel lymph nodes in adult patients with breast cancer, melanoma, or localised squamous cell carcinoma of the oral cavity.

Lymphoseek® has been specifically designed to target, bind to and be retained in sentinel lymph nodes, the first lymph node (or group of nodes) to which cancer cells are most likely to spread from a primary tumour. Lymphoseek® has a false negative rate of 2.6% in T1-T4cN0 oral squamous cell carcinoma (OSCC). It detected sentinel lymph nodes in 98% of patients with Tis, Tx or T1-T4cN0 breast cancer and T1-T4cN0 melanoma

Lymphoseek® offers particular value in identifying lymphatic drainage from tumours in the floor of the mouth (underneath the tongue) which can prove especially difficult. Currently up to 70-80% of patients with early oral cancer receive elective neck dissection surgery, a major procedure which could be avoided by using sentinel lymph node biopsy (SLNB) for staging.

Peter Martin, COO at Norgine commented: “Making Lymphoseek® available to patients demonstrates our commitment to improving patients’ quality of life with access to new innovative specialist diagnostic tools and treatments. Norgine wants all eligible patients suffering from oral cancer, breast cancer or melanoma to have their cancers accurately staged using sentinel lymph node biopsy with Lymphoseek®. This will result in a reduction in unnecessary surgical interventions that can optimise the use of healthcare resources and improve patients’ outcomes.”

Head and neck cancer is the seventh most common type of cancer in Europe. It is about half as common as lung cancer, but twice as common as cervical cancer. There were more than 150,000 new patients diagnosed in Europe in 2012.

September, 2017|Oral Cancer News|

Simple test can detect oral cancer in minutes

Source: www.click2houston.com
Author: Click2Houston.com Staff

Nearly 50,000 people will be diagnosed with oral cancer in the United States this year, and those numbers are expected to rise. Now, a simple, non-invasive test may soon be available to detect this deadly cancer early, with the hope of saving more lives.

Jeffrey Stanger was enjoying the good life when a trip to the dentist led to a frightening diagnosis. A biopsy revealed Jeffrey had oral cancer.

“When we refer to oral cancer, I’m talking about tumors involved in the mouth or the throat,” otolaryngologist, Dr. Elizabeth Franzmann explained.

Franzmann said cases of oral cancers are on the rise in this country due to the human papilloma virus or HPV. She says this type of cancer can be difficult to detect early on.

“So we are in better need of screening tools for this disease that are simple and inexpensive,” Franzmann added.

Franzmann and her team discovered that a molecule called CD44 plays an important role.

“We published a paper that showed that sure enough the levels in cancer patients were elevated compared to controls,” Franzmann said.

From there they developed a simple oral rinse test called OncAlert that can be used right in the dentist’s office.

Franzmann, showing the product, explained, “This protein pad here will turn a certain color of green.”

The green color means shows a person is at high risk. Jeffrey says this simple test can be a life saver.

“So you can detect it in very earlier stages,” he explained.

Jeffrey had surgery to remove the cancer, and is back smiling and enjoying life.

In spring of 2017 Vigilant Biosciences opened their FDA trial for the U.S. version of the OncAlert rapid test. A similar test that’s sent to the lab is already available here in the U.S. Both tests are made by Vigilant Biosciences, which recently received a federal grant from the National Institutes of Health for Oral Cancer Research.

September, 2017|Oral Cancer News|

Alcohol industry ‘playing down’ risk of cancer by using tobacco industry tactics

Source: news.sky.com
Author: Paul Kelso, Health Correspondent

The alcohol industry is misleading the public by downplaying the risk of cancer through similar tactics to the tobacco industry, researchers say.

Liquor bottles in grocery store

A study led by the London School of Hygiene and Tropical Medicine (LSHTM) and Sweden’s Karolinska Institutet found the industry is using “denying, distortion and distraction” strategies to minimise evidence.

Researchers analysed information relating to cancer on the websites and documents of 28 alcohol industry organisations between September and December last year, finding that most showed “some sort of distortion or misrepresentation” of evidence.

The industry most commonly presented the relationship between alcohol and cancer as highly complex, implying there was no evidence of a consistent or independent link, according to the study.

Other tactics included denying that any relationship existed or claiming that there was no risk for light or moderate drinking, as well as presenting alcohol as just one risk among many.

Alcohol consumption is an established risk factor for a range of cancers, including oral cavity, liver, breast and colorectal cancers, and accounts for about 4% of new cancer cases annually in the UK.

The latest British government advice on alcohol, issued last year, makes an explicit link between cancer and alcohol.

It states: “The risk of developing a range of health problems (including cancers of the mouth, throat and breast) increases the more you drink on a regular basis.”

During the consultation phase the alcohol industry challenged the link with cancer.

The authors of the report, published in the Drug and Alcohol Review journal, said it was important to highlight that those who drink within the recommended guidelines – not more than 14 units a week for both men and women – “shouldn’t be too concerned when it comes to cancer”.

Mark Petticrew, Professor of Public Health at the LSHTM and the study’s lead author, told Sky News: “The information, on balance, across organisations we looked at seems to be quite extensively inaccurate or misrepresents the evidence.

“The evidence linking alcohol consumption and cancer is reasonably clear and has firmed up over recent years. The information on these websites, given out by alcohol bodies, appears to be not representing that evidence base, which is quite consistent.

“We know the tobacco industry attempted to confuse the relationship between lung cancer and smoking and put out a lot of very distracting information. We see similar types of argument use in these alcohol industry websites.”

Institute of Alcohol Studies chief executive Katherine Brown said: “This report shows that, like the tobacco industry before them, alcohol companies are misleading consumers about the evidence linking their products to cancer.

“We cannot rely on a profit-driven industry to promote public health. Consumers have a right to know the truth about alcohol and cancer, so they can make fully informed decisions about their drinking.”

The alcohol industry denied the report’s findings.

Glasses of light and dark beer on a pub background.

Drinkaware, a charitable trust funded by drinks manufacturers, said: “Its recent review of Drinkaware’s cancer information, which is extensive, has confirmed that the information we are providing accurately reflects the most recent research evidence.”

Henry Ashworth, president of the International Alliance for Responsible Drinking, said: “We do not agree with the conclusions reached in this paper. We believe in sharing the current state of the scientific evidence and stand by the information that we publish on drinking and health.”

Chris Snowdon, head of lifestyle economics at the Institute of Economic Affairs, said: “This is a diatribe disguised as a study that seeks to create a false narrative in which businesses always lie and anti-alcohol campaigners always tell the truth.

“We need to have sensible and evidence-based information about the risks of alcohol. The risks associated with cancer are not the biggest risks when it comes to drinking, the bigger risks are to do with violence, drink-driving and liver cirrhosis.

“It’s not cancer, so I’m not convinced that actually people understood fully what the risks associated with drinking are in terms of cancer when it doesn’t have an effect on people’s consumption of it at all.”

September, 2017|Oral Cancer News|

World Trade Center responders might face greater risk of HPV throat and tongue cancer

Source: medicalxpress.com
Author: provided by Rutgers University

Firefighters at the World Trade Center were exposed to tons of toxic dust and debris that blanketed Manhattan on 9/11. Credit: Shutterstock

Researchers at Rutgers University – investigating the causes of head and neck cancers in World Trade Center rescue and recovery workers – will take the lead in a study to determine whether the responders are at a greater risk for human papillomavirus (HPV)-related throat and tongue cancer because of their exposure to toxic dust and debris.

“If we find that the prevalence of HPV is higher in World Trade Center exposed rescue workers it could mean that they have an increased likelihood of infection with HPV or have less of an ability to be able to clear this common infection naturally,” said Judith Graber, assistant professor of epidemiology in the School of Public Health.

HPV is the most common sexually transmitted infection in the United States, according to the Centers for Disease Control and Prevention, with most infections going away on their own. There is also now a vaccine to prevent HPV given to adolescents and teens. This is a new vaccine not given to adults and rates of vaccination have been low in the US.

While HPV-related oropharyngeal cancer, which includes throat, tonsils, back of tongue and soft palate, is relatively small, the number of HPV throat and tongue cancers are expected to increase and surpass HPV-related cervical cancers by 2020.

Graber said oropharyngeal cancer – which has a lower survival rate – is among the diseases which pose great risk for WTC rescue and recovery workers, who appear to have a greater incidence of throat and tongue cancer. Surviving patients, often left disfigured after treatments, are at a higher rate for depression, unemployment and suicide compared with other cancer patients, according to the study.

While the prevalence of HPV in the United States among people age 69 and younger is estimated at less than 10 percent, Graber said research indicates that 80 percent of all tumors found in this type of cancer are infected with HPV, some which can cause cancer.

“The symptoms, risk factors and exposure history could help in early prevention of this very devastating cancer,” said Graber.

The new Rutgers study will use tissue samples provided by the World Trade Center Biorepository at Mount Sinai from WTC workers diagnosed with oropharyngeal cancer and compare to tissue samples of people being treated for the disease at University Hospital in Newark.

This research is a spinoff of a two-year federally funded study examining risk factors for all head and neck cancers among WTC responders. Graber and her colleagues, including co-principal investigator, Mark Einstein, professor and chair department of OBGYN & Women’s Health at Rutgers New Jersey Medical School, are hoping to discover opportunities for early detection for these potentially debilitating diseases.

“HPV is very common, but cancers related to HPV are uncommon,” said Einstein. “Understanding the relationship between HPV and the development of oropharyngeal cancer is of critical importance so we can prevent and target this cancer better with novel therapies”.

What researchers need to determine in this new study, Graber said, is whether the higher incidence of the throat and tongue cancer is due to the fact that this group is being closely monitored, because of respiratory exposure after 9/11 or as a result of an HPV infection that creates a problem for a weakened immune system.

The information is critical, Graber said, in the quest to design a more definitive study to determine how and why these cancers are developing among those exposed during the rescue, recovery and clean-up efforts at the World Trade Cente

September, 2017|Oral Cancer News|

What’s next after creating a cancer-prevention vaccine?

Source: www.scientificamerican.com
Author: Dina Fine Maron

A winner of this year’s Lasker Awards talks about his work with HPV

Imagine a vaccine that protects against more than a half-dozen types of cancer—and has a decade of data and experience behind it.

We have one. It’s the human papillomavirus (HPV) vaccine, and it was approved for the U.S. market back in June 2006. It can prevent almost all cervical cancers and protect against cancers of the mouth, throat and anus. It also combats the sexually transmitted genital warts that some forms of the virus can cause.

On Wednesday, two researchers who completed fundamental work on these vaccines received one of this year’s prestigious Lasker Awards, a group of medical prizes sometimes called the “American Nobels.” Douglas Lowy and John Schiller, whose research provided the basis for the HPV vaccine, were selected alongside a researcher who separately unraveled key aspects of metabolic control of cell growth. Planned Parenthood was also given an award, for its public service. Lowy and Schiller, who both work at the U.S. National Cancer Institute (NCI), received the Lasker for their research on animal and human papillomaviruses—work that enabled the development of a vaccine against HPV-16 type, a form of the virus that fuels many HPV malignancies. The duo’s experiments proved that the vaccine is effective in animals, and they also conducted the first clinical trial of an HPV-16 vaccine in humans. That gave pharmaceutical companies the evidence they needed to invest in their own vaccines designed to protect against multiple kinds of HPV, and ultimately led to the versions administered around the world today.

Yet HPV shots have had a difficult run. Despite overwhelming evidence of their safety and effectiveness, in some developed countries—including the U.S.—HPV inoculations face opposition from individuals and groups that fear the shots are still too new and unproved to use on their children. The HPV vaccine also faces another hurdle beyond other routine pediatric shots: the virus is transmitted via sexual contact—which some parents and communities believe teens should not or will not have, and thus that the shots should not be mandatory. (The U.S. Centers for Disease Control and Prevention [CDC] currently recommends administering two doses of the vaccines to children 11 to 12 years old, administered at least six months apart.)

Scientific American spoke with Schiller, a virologist, about his and Lowy’s award-winning HPV research, their future plans and how to combat anti-vaccine attitudes.

[An edited transcript of the interview follows.]

What’s the biggest hurdle to getting more coverage with the HPV vaccine?
The biggest problem is actually not in the West or most developed countries; it is in the lower- and middle-income countries because of availability there and vaccine prices that limit availability. In those settings vaccine acceptance is actually very high. But those settings present the biggest problem, since some 85 percent of cervical cancers occur in low-resource settings. In the more developed countries there are many different factors involved [in vaccine hesitancy], and they differ by country. In the U.S. it is more about fear of vaccines in general. And there are some issues with HPV vaccines specifically related to this being about a sexually transmitted disease.

So far, more than 270 million doses of HPV vaccines have been distributed worldwide. But in the United States, by 2015 only 28 percent of teen males and 42 percent of teen girls had received the full course of three shots then recommended by the CDC. How can the science community help combat HPV vaccine hesitancy?
There are quite a few studies that show one of the biggest issues is that the vaccine is not being promoted sufficiently by pediatricians and general practitioners. If you look at other vaccines like for meningitis and hepatitis B—which are also administered to adolescents and could be given in the same visit as HPV—they are given at greater rates than HPV. So, there is some disconnect in communication between pediatricians and parents there. Part of the problem here is that the HPV vaccine is a prophylactic vaccine to prevent a disease—cervical cancer—that those providers never see. Obstetrician-gynecologists see it, but pediatricians don’t, which is the opposite of most other childhood or pediatric vaccines. Right now it’s being singled out as something special instead of treated as a routine childhood or adolescent vaccine. But we’ve had this vaccine for 10 years now and it’s not the new kid on the block anymore.

Mounting evidence suggests that among people who feel vaccines are unsafe, any new data showing that they arereally safe does not move the needle to convince them. So, what can be done?
My feeling is that there is a certain percentage of people who, no matter what facts you present to them, they are just not going to be convinced. Quite frankly it doesn’t pay to spend a lot of resources trying to convince that relatively small fraction. What we need to focus on is a much larger fraction of the population who aren’t having their kids vaccinated for reasons like convenience—like it’s a hassle—or they just need a bit more information to make them comfortable. People against all vaccines, those people would not be convinced to get an HPV vaccine so it’s not worth spending a lot of resources on them. I think one of the things that would increase HPV vaccine coverage would be allowing people to get them at their local CVS. I’m not an expert on this, but I have a daughter who as a teen spent much more time at the local CVS than at her local Kaiser clinic. Different states have different laws about which vaccines can and can’t be delivered at pharmacies—but if someone could go get an HPV vaccine at the same place they get their flu vaccine, presumably it would lead to an uptick.

I see you studied molecular biology as an undergrad at the University of Wisconsin–Madison. Did you always want to work on vaccines?
No, absolutely not. When I first started out I was an academic purist and thought you should study knowledge for its own sake. I was fascinated by molecular biology. When I first heard about the way metabolism works in bacteria, plants and humans, that just wowed me because that was a common feature of all life. I just wanted to study that. I thought people who did translational work were sort of selling out to the man—this was in the 1970s. I didn’t get interested in vaccines until much later. Now, I’m very fascinated with translational research.

So, what changed?
It was a very gradual thing. To this day we still do basic research, and it’s still intrinsically valuable to do basic research because you don’t know when it will lead to a transformational breakthrough.

What led you to work on HPV?
When I had just joined the field, suddenly there was this discovery that made papilloma viruses important for human health as opposed to just an understanding of how cells become cancerous. I had joined Doug Lowy’s lab at the National Cancer Institute as a postdoc back in 1983, and the second lecture I went to there was by Harald zur Hausen—who later won the Nobel Prize—and his lecture was saying “eureka! We found a virus that seems to cause 50 percent of cervical cancers”—and that virus turned out to be a human papilloma virus strain, HPV-16. So basically we went from looking at a model about how a normal cell transforms to become carcinogenic to something probably involved in causing human cancer. It was somewhat serendipitous.

What are you working on now?
One thing we are doing at the NCI, and cosponsored by the Bill & Melinda Gates Foundation, is testing if one dose of HPV vaccine is enough to provide long-term protection. It would be transformative, especially in the developing country setting, if you could just have one dose at a younger age. This new trial is going to be done in Costa Rica in collaboration with the Costa Rican government. That’s the site where we had done a prior pilot trial that suggested one dose may be enough.

We are also looking into cancer immunotherapy work. It turns out that these virus-like particles that we work with for the HPV vaccine—these are typically the outer shell of a virus, like from the HPV-16 strain or other animal, or human papilloma virus particles—have a unique ability to infect tumor cells and bind to them specifically. So we are using that knowledge to develop cancer therapies that are broad-spectrum. It turns out these cancers, like melanoma, do bind these particles, specifically.

One other thing we are doing is trying to develop vaccines that would treat herpes simplex infections and HPV infections in the female genital tract. Again, this would take advantage of these virus-like particles’ structures.

Last year I interviewed Michael Sofia, who won a Lasker Award for his hepatitis C vaccine work. The name of that vaccine, sofosbuvir—brand name Sovaldi—is a nod to his last name. But the National Institutes of Health (NIH) do a lot of early-stage research, and then it’s passed off to private companies that develop it further. Your name isn’t part of the HPV vaccines Gardasil or Cervarix, for example. Is it frustrating doing a lot of that behind-the-scenes work?
It’s funny because I would never have thought of that. It would have never entered my mind to name a vaccine after ourselves. We are so used to doing this translational work. My job is to move a project along so it’s interesting enough for a company to invest hundreds of millions of dollars for the benefit of large numbers of people. NIH doesn’t have the money to do phase III trials for lots of drugs, and even if they did it wouldn’t lead to all the drugs we need—because NIH wouldn’t have the money to develop them. This translational and basic research is what NIH does best. That work is way too fraught with failure for companies to do it all. It has to be done in the public sector, and then when things look more promising companies can take it over.

What advice would you offer someone considering becoming a scientist now?

It’s got to be a passion because being a scientist—especially early in your career—is more a lifestyle than occupation. You have to really want to do it, because there is a lot of uncertainty—especially about running your own lab and getting funding. Success and failure can be on a knife’s edge sometimes. The other thing is that you need to be strategic about thinking of what you want to go into, and that’s hard for young people because they don’t have the perspective: There are some fields just opening up ripe for discoveries. And there are some areas that are very mature, that we have been working on for a long time, where there are a lot of scientists working already—so the chances of making a big impact are lower. From my own life, this is like when we started with human papilloma viruses. When I went into this field, we had just been given the tools to study them and so it seemed like a great opportunity to get involved. In some ways it’s best if you can pick an emerging field with new tools to answer big questions. But you have to pick something you are really interested in and go with it.

The other thing I’d say is read a lot. Now with PubMed and access to all these journals there is no excuse for not knowing the background in something that basically has already been done. Young people tend to want to get out and do experiments, but a few days searching PubMed may save someone years of work trying to reinvent the wheel.

Right now, what would you say is the biggest challenge—or one of the biggest challenges—that needs to be solved?
That’s a really tough one. I think as scientists we are all sort of locked into the things we study. I could say cancer, obviously. But Alzheimer’s is something we obviously need to solve. HIV infection. All these different things. One of the things that really needs to be solved in terms of the whole scientific enterprise now is stable funding. Right now we are in a situation where there are too many good scientists—especially young scientists—competing for a limited pot of money. So you lose some good people because there’s not enough money to go around. Also, people are forced to do relatively mundane things that are really a methodological extension of something they’ve done before instead of something truly transformative that would have a large chance of failure. Grant reviewers are looking at something likely to succeed and move the field incrementally, or something transformative that may have a high chance of failure, and have to make those decisions. This is an issue across the sciences. The obvious solution would be to have more funding, but then that raises the question about how to do that. And I’m not a politician.

What, if anything, does this Lasker Award do for your work?
Quite honestly, probably nothing, because one of the nice things about being part of intramural research [at NIH] is that I have stable funding. I’ve had six people in my lab for the last 25 years, so this won’t lead to more grants or me doubling the size of my lab, or anything like that. I’m happy with my moderate-sized lab and collaborations with a lot of great people. That’s why I’m here. Every four years we have a site visit, which is a retrospective review of “what have you done for us lately,” and if it’s reasonable I will continue to get funding. So the award won’t affect my research career much at all.

Right now, some in the scientific community fear amid this political climate that facts matter less than they once did and thus science matters less. What’s your take on that?
Obviously, my perspective is science matters a lot. I really can’t comment on what’s happening in the country overall—and whether this is something that is pervasive where science is really held in less esteem, or it’s that there is a vocal minority being heard a lot now. I would hope it’s the latter.

September, 2017|Oral Cancer News|

Personalised cancer treatment

Source: medicalxpress.com
Author: University of Oslo

In Norway, more and more people are being affected by cancer of the mouth and throat. In recent years, the incidence has increased but the mortality has remained the same. Cisplatin is one of the most commonly administered cytostatics for this patient group. At the start of treatment, the drug works well. Gradually, though, most patients experience that the tumour develops resistance against this drug and the prognosis for survival then becomes very poor.

In her PhD thesis, Jian Gao wanted to find out how the cancer cells could protect themselves against this cytostatic i.e. what is the underlying mechanism of resistance.

She therefore cultured various cancer cell lines derived from oral cavity which were given differing doses of the cytostatic cisplatin. A cancer cell line is cultured from patients’ cancerous tumours and can live indefinitely in the laboratory. These types of cell lines are used to examine the biology and the changes that have resulted in the development of cancer. Because the cancer cell lines divide in the laboratory, they can also adapt to new growth conditions, for example by becoming resistant to the cytostatic cisplatin in the same way as the cancer tissue in the patients.

“First, I had to find those cancer cells that were sensitive to the cytostatic,” explains Jian Gao. By identifying the sensitive cancer cell lines that I could make resistant in the laboratory, I could then study which changes took place in the cells as they changed from being sensitive to being resistant,” clarifies Gao.

Cytostatic for cancer cell lines

“During this process I found two different cancer cell lines. At the beginning, I gave them a dose of cytostatic that was strong enough to kill half of the cancer cells. This dose was increased each week, and after eight months both types of cancer cells were resistant to the cytostatic, cisplatin,” explains Gao.

Next, these cells had a resting period from any type of treatment. Gao wanted to see whether this resistance could be reversed by the pause in cytostatic treatment. However, it became apparent that the pause did not have any effect and the cells were permanently resistant to cisplatin. The resistant cell lines had changed permanently.

“Since I have two cell types that I knew were resistant, and I could now compare these cell lines with the original sensitive cancer cell lines,” comments Gao.

To compare gene expression in the cells, Gao used a technique that studies the expression of about 21,000 genes, a so-called mRNA microarray. This technique was used to look at changes in gene expression in the resistant cancer cell lines and then compare them with the gene expression in the original sensitive cancer cell lines.

Up-regulated genes

Only three genes were found to be up-regulated in both of the resistant cell lines. Of these genes, Gao decided to look at a cytokin, interleukin 6 (IL-6), which is a signal molecule that is often up-regulated in cancer, and which is associated with a poor prognosis and cisplatin resistance in several types of cancer.

By investigating expression of the IL-6 gene in head and throat cancers in 399 patients and then comparing this with survival, Gao and her co-workers found that, after treatment with the cytostatic cisplatin, the patients with cancer tumours with the up-regulated interleukin 6 gene did not have a better prognosis for survival.

Apparently, such cancer tumours were resistant to cisplatin. However, detailed mapping of the resistant cancer cell lines revealed that IL-6 in itself did not make the cancer cisplatin resistant. The effect had to be exerted via currently unknown mechanisms, possibly in the interaction between the cancer and IL-6 stimulation in the surrounding connective tissue.

Growth factors

Connective tissue can produce growth factors which cause the cancer to grow. There are a number of different growth factors and, of the eight known epithelial growth factors, Gao and her co-workers could demonstrate a relationship between the tumour’s gene expression in four of these epithelial growth factors and survival. The four growth factors were: Amphiregulin, epidermal, heparin-binding EGF-like growth factor and betacellulin. Could increased production of these growth factors explain cisplatin resistance?

Jian Gao’s research showed that if these growth factors were up-regulated, there was a high probability that the patient would not survive. At the same time, no relationship was found between cisplatin resistance in the cancer cell lines and the production of these growth factors.

However, the researchers could demonstrate that the more of these four growth factors a tumour expressed, the poorer the prognosis for the patient. By quantifying the amount of mRNA in the tumour tissue, Gao and co-workers could predict the patient’s prognosis considerably more accurately than the TNM system, which is the traditional method used to determine the stage of a cancer. The level of these four growth factors could predict how long even the most ill patients with distant metastases would live.

These growth factors have a common receptor in the so-called EGF receptor family. Currently, there are a number of drugs in use in patient treatment that can block this receptor. For patients whose cancers demonstrate high expression of these growth factors, it could potentially be particularly appropriate to use these medicines to reduce the growth of the cancer and increase the patient’s chances of survival.

In the last part of her PhD thesis, Gao tried to find the various “inhibitors” that could affect cisplatin resistance. After several trials with various signal and receptor inhibitors, she finally found that a drug called AG825, which inhibits the activity of an EGF receptor family member (HER 2), could reduce cisplatin resistance in four different cancer cell lines. This occurred by increasing the ability of cisplatin to trigger the cells’ self-destruct programme (apoptosis).

These drugs are already in use to treat patients with other types of cancer and, even though the details of the mechanism must be investigated in more detail, Gao and co-workers have demonstrated the probability that treatment with a cytostatic combined with “inhibitors” of the cancer cells’ protective mechanism will be advantageous. This could considerably improve the effect of the cytostatic cisplatin and thereby improve the prognosis for survival for patients with cancer of the head or throat.

But a lot of work still remains, and the journey from cell line reactions in the laboratory to how cancer cells in patients react to the same type of combined therapy is often long. Only more research can provide the answer to whether this is a navigable route to a more effective, personalised treatment of cancer of the head and throat.

September, 2017|Oral Cancer News|

Gliknik announces dosing of first patient in phase 2 trial targeting prevention of recurrence of high-risk oral cavity cancer

Source: www.prnewswire.com
Author: press release

Gliknik Inc. today announced that clinicians have enrolled and dosed the first of 80 patients in the company’s phase 2 clinical trial assessing the efficacy and safety of biropepimut-S (GL-0817), an immunomodulatory therapeutic targeting the prevention of recurrence of squamous cell cancer of the oral cavity in patients at high risk of recurrence after surgery, chemotherapy, and radiation.

“We are pleased to enroll the first patient in this phase 2 trial of biropepimut-S, which will further our understanding of the potential role of this advanced-design cancer vaccine with immune enhancing adjuvants in high-risk oral cavity cancer,” said Jeff Herpst, Senior Director of Clinical Development at Gliknik.

High-risk oral cavity cancer is associated with a recurrence rate of approximately 70% within three years of the time of surgical resection despite adjuvant chemoradiotherapy. Unfortunately, only a small percent of patients respond to the clinical options currently available for physicians to use in treating such patients who recur.

“With recurrent oral cavity cancer being so difficult to treat, now is an opportune time to assess how useful and safe biropepimut-S may be in protecting individuals from recurrence of high-risk oral cavity cancer,” said David Block, CEO of Gliknik. “The goal of the study is to see if we can activate the individual’s immune system to eliminate residual cancer cells that cannot be seen by current imaging methods, thereby avoiding clinical recurrence. We are finding that physicians and patients are interested in clinical trials addressing this significant unmet medical need.”

August, 2017|Oral Cancer News|

HPV-related oral cancers have risen significantly in Canada

Source: www.ctvnews.ca
Author: Sheryl Ubelacker, The Canadian Press

The proportion of oral cancers caused by the human papillomavirus has risen significantly in Canada, say researchers, who suggest the infection is now behind an estimated three-quarters of all such malignancies. In a cross-Canada study, published Monday in the Canadian Medical Association Journal, the researchers found the incidence of HPV-related oropharyngeal cancers increased by about 50 per cent between 2000 and 2012.

“It’s a snapshot of looking at the disease burden and the time trend to see how the speed of the increase of this disease (is changing),” said co-author Sophie Huang, a research radiation therapist at Princess Margaret Cancer Centre in Toronto.

Researchers looked at data from specialized cancer centres in British Columbia, Alberta, Ontario and Nova Scotia to determine rates of HPV-related tumours among 3,643 patients aged 18 years or older who had been diagnosed with squamous cell oropharyngeal cancer between 2000 and 2012.

HPV is the most common sexually transmitted infection worldwide. Most people never develop symptoms and the infection resolves on its own within about two years.

“In 2000, the proportion of throat cancer caused by HPV was estimated at 47 per cent,” said Huang. “But in 2012, the proportion became 74 per cent … about a 50 per cent increase.”

Statistics from a Canadian Cancer Society report last fall showed 1,335 Canadians were diagnosed in 2012 with HPV-related oropharyngeal cancer and 372 died from the disease.

HPV is the most common sexually transmitted infection worldwide. Most people never develop symptoms and the infection resolves on its own within about two years. But in some people, the infection can persist, leading to cervical cancer in women, penile cancer in men and oropharyngeal cancer in both sexes.

Most cases of HPV-related oral cancer are linked to oral sex, said Huang, noting that about 85 per cent of the cases in the CMAJ study were men.

HPV-related tumours respond better to treatment and have a higher survival rate than those linked to tobacco and alcohol use, the other major cause of oral cancer, she said, adding that early identification of a tumour’s cause is important to ensure appropriate and effective treatment.

While some centres in Canada routinely test oral tumours to determine their HPV status, such testing is not consistent across the country, the researchers say.

In the past, physicians generally tended to reserve tumour testing for cases most likely to be caused by HPV – among them younger males with no history of smoking and with light alcohol consumption – to prevent an unnecessary burden on pathology labs.

“Only as accumulating data have supported the clinical importance of HPV testing has routine testing been implemented in most (though not all) Canadian centres,” the researchers write.

The study showed that the proportion of new HPV-related oral cancers rose as those caused by non-HPV-related tumours fell between 2000 and 2012 – likely the result of steadily declining smoking rates.

Huang said males tend to have a weaker immune response to HPV than do females, which may in part explain the higher incidence of oral cancers linked to the virus in men.

HPV vaccines given to young people before they become sexually active can prevent infection – and the researchers say both boys and girls should be inoculated.

Currently, six provinces provide HPV immunization to Grade 6 boys as well as girls, with the other four provinces set to add males to vaccination programs this fall, said Huang.

“So vaccinating boys is very important because, if you look at Canadian Cancer Society statistics (for 2012), HPV- related oropharyngeal cancer in total numbers has already surpassed cervical cancers,” she said.
“The increase of HPV-related cancer is real, and it’s striking that there’s no sign of a slowdown.”

August, 2017|Oral Cancer News|

U.S. FDA removes clinical hold on CEL-SCI’s phase 3 head & neck cancer trial

Source: www.businesswire.com
Author: press release

CEL-SCI Corporation today announced it has received a letter from the U.S. Food and Drug Administration (FDA) stating that the clinical hold that had been imposed on the Company’s Phase 3 cancer study with Multikine* (Leukocyte Interleukin, Inj.) has been removed and that all clinical trial activities under this Investigational New Drug application (IND) may resume.

Multikine is being studied as a potential first-line (before any other cancer treatment is given) immunotherapy that is aimed at harnessing the patient’s own immune system to produce an anti-tumor response. Nine hundred twenty-eight (928) newly diagnosed head and neck cancer patients have been enrolled in this Phase 3 cancer study and all the patients who have completed treatment continue to be followed for protocol-specific outcomes in accordance with the Study Protocol.

The study’s primary endpoint is a 10% increase in overall survival for patients treated with the Multikine treatment regimen plus standard of care (SOC) versus those who receive SOC only. The determination if the study’s primary end point has been met will occur when there are a total of 298 deaths in those two groups. Current SOC for this indication is surgery, followed by radiation therapy alone or followed by concurrent radio-chemotherapy.

There is a clear and unmet medical need for a new treatment in this indication as the last FDA approved treatment for advanced primary head and neck cancer was over 50 years ago. The FDA has also designated Multikine an Orphan Drug for neoadjuvant therapy in patients with squamous cell carcinoma of the head and neck (SCCHN).

About Head and Neck Cancer
Head and neck cancer describes squamous cell carcinomas located inside the neck, mouth, nose, and throat. According to the World Health Organization, the annual incidence of head and neck cancer is approximately 550,000 cases worldwide, with about 300,000 deaths each year. Risk factors involved with head and neck cancer include heavy alcohol use, tobacco use, and the cancer causing type of human papilloma virus (HPV).

About CEL-SCI Corporation
CEL-SCI’s work is focused on finding the best way to activate the immune system to fight cancer and infectious diseases. The Company has operations in Vienna, Virginia, and in/near Baltimore, Maryland.

August, 2017|Oral Cancer News|