surgery

Anti-malarial drug can make cancer chemotherapy more effective

Source: medicalxpress.com
Author: Emma McKinney, University of Birmingham

Scientists at the University of Birmingham have found an anti-malarial drug was effective in treating head and neck cancer in mice.

The drug quinacrine was used extensively to prevent and treat malaria in soldiers fighting in mosquito-ridden areas during World War Two. It is similar to the quinine that makes tonic water glow, has minimal side-effects, and is now used for treating parasite infections and other conditions.

Each year around 11,900 people are diagnosed with head and neck cancer in the UK. Current treatment relies heavily on debilitating surgery and toxic chemotherapy, but despite this, it has a poor outcome with three to seven in 10 people surviving their disease for five years or more.

The drug, quinacrine, was tested through a number of methods, including on cell cultures, in tumour biopsies from patients with head and neck cancer, and in mice.

The research results, published in Oncotarget, show that in mice quinacrine can make standard chemotherapy more effective—suggesting a lower dose may be used, reducing toxic side effects.

The results also showed the drug to be effective at reducing the growth of cancer cells grown in the lab, and in tumors.

Significantly, the research in mice showed a combination therapy of quinacrine and chemotherapy, and so allowed for the chemotherapy dose to be halved while still maintaining the same impairment of tumor growth.

Lead author Dr. Jennifer Bryant, of the University of Birmingham’s Institute of Head and Neck Studies and Education, said: “This is important research in the laboratory and demonstrates the real potential in repurposing drugs.

“The team is now looking to translate these research findings into a clinical trial for head and neck cancer patients.”

Corresponding author Professor Hisham Mehanna, Director of the Institute of Head and Neck Studies and Education at the University of Birmingham and Consultant Head, Neck and Thyroid Surgeon at University Hospitals Birmingham NHS Foundation Trust, said drug repurposing is particularly exciting due to known safety in humans and low cost, which mean they can be rapidly translated from the lab to the clinic.

He added: “Head and neck cancer patients have limited treatment options, often associated with severe, potentially life-threatening, side effects, it is important, therefore, that we find different treatments.

“My team has developed a drug repurposing platform called “AcceleraTED’ which assesses drugs that treat other non-cancerous conditions and have been approved by the Food and Drug Administration and the European Medicines Agency to see if they have the potential to be effective anti-cancer agents against head and neck cancer.

“This research is an example of the success we are having in the laboratory through this platform in identifying promising drugs that can be candidates to be used in patients in clinic.”

October, 2019|Oral Cancer News|

Psychological impact of head and neck cancers

Source: pharmafield.co.uk
Author: Emma Morriss

Bristol-Myers Squibb (BMS), in partnership with patient groups The Swallows and the Mouth Cancer Foundation, have announced the results from a patient survey into the psychological impact of head and neck cancers. The research explored the long-term burden of treatment on head and neck cancer patients.

After undergoing treatment for head and neck cancer, which can include surgery, chemotherapy or radiotherapy, many patients report an ongoing impact on their day-to-day life. However, 55% of the 118 patients surveyed indicated they did not receive the right level of information in preparation for the complications encountered from treatment.

There are around 11,900 new head and neck cancer cases in the UK every year and the incidence of head and neck cancer has increased by 32% since the early 1990s.

Following treatment, the survey showed 56% of patients had problems with simple things like swallowing, often experiencing severe pain, while two-thirds of patients experienced changes in their voice or speech. The survey also showed self-reported change from pre- to post- treatment in vital areas including a drop in the ability to communicate (37%), memory loss (21%), and trouble sleeping (20%).

As well as physical symptoms, treatment can have severe implications on mental health too. 52% of patients reported feelings of anxiety before treatment, which only reduced to 48% following treatment. However, emotional and psychological support was only offered to 46% of patients.

A majority of patients did receive access to a clinical nurse specialist, however there was still 23% who were not offered this service. Clinical nurse specialists use their skills and expertise in cancer care to provide physical and emotional support, coordinate care services and inform and advise patients on clinical as well as practical issues, which have been shown to lead to more positive patient outcomes.

“These results show the impact treatment may have on head and neck cancer patients. The continued problems and symptoms experienced by patients after treatment significantly impacts patients’ daily life. We also know physical disfigurement can increase social anxiety. It is important that we raise the awareness of this and work together to provide solutions to improve and support patient outcomes.” said Mouth Cancer Foundation, Clinical Ambassador, Mr Mahesh Kumar.

“With the incidence of head and neck cancers increasing, it is vital we understand what we can do to help patients. We are so pleased to have worked in collaboration with BMS and the Mouth Cancer Foundation to help raise awareness of this disease and understand where patients might need more help to reduce the impact on their lives. We know head and neck cancers, and the associated complications, do not get a lot of attention so it’s crucial for awareness days such as World Head and Neck Cancer Day to be used to shine a light on the disease. By doing so, it will help to improve detection, treatment and outcomes for patients.” commented Chris Curtis, Chairman of The Swallows.

Head and neck cancer: Novel treatment approaches

Source: www.curetoday.com
Author: staff

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S, and Itzhak Brook, M.D., M.Sc., board members of the Head and Neck Cancer Alliance, share insight into the role of novel treatment approaches like immunotherapy, robotic surgery and de-escalation in the management of cancers of the head and neck.

Transcript:
Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: Dr. Brook, traditionally the treatment for head and neck cancer has been surgery, radiation, chemotherapy or some combination of those three. But there are some new and emerging treatment approaches to head and neck cancer along with many other cancers. Can you tell us a little bit about immunology? What is immunotherapy in the care of the head and neck cancer patient?

Itzhak Brook, M.D., M.Sc.: Most days, we don’t get cancer because our immune system is like the police department of our body. They detect cancer early and eliminate it. Unfortunately, in the case of cancer, the cancer cells can fool the immune system, and they go undetected and cause the disease. The main advantage of immunotherapy is that we are using the body’s defenses, the immune system, to kill the cancer in a much better way than the chemotherapy. Chemotherapy destroys the cancer cells, but it also affects the body cells. Immunotherapy is more precise. It is directed only to the cancer cells, so the rest of the body stays unscathed. That’s the beauty of immunotherapy. So, immunotherapy is an evolving field in cancer. They have many, many new drugs in the pipeline, and many studies are being done. But right now, there are several drugs that are good and seem to help in a patient with cancer, cancer that has already spread or that surgery cannot reach. The body’s own immunity would reach it.

One of them is monoclonal antibodies that were developed specifically for the cancer cells, and the other one is checkpoint inhibitors, which overcome the attempt by the cancer cells to fool the immune system and protect the cancer cells from their own immunity. So, by blocking those checkpoints, the body’s own immunity comes in and destroys the cancer cells. Those drugs are very promising because first of all, they are more effective in getting only the cancer cells. They do cause fewer side effects, and we are hopeful that they would be the new armamentarium that we will have for head and neck cancer.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: So, would you say that’s something you should ask your physician about to find out what clinical trials and what types of medications are offered for your specific type of cancer at the time of diagnosis?

Itzhak Brook, M.D., M.Sc.: Absolutely, and that is depending on your own illness, on the seriousness or stage of the illness. And your physician would be able to consult the right specialist to tailor the specific treatment for you, and that’s very important because now we have a new tool that can augment the chemotherapy. And many of those treatments are given in combination. Conventional treatment with chemotherapy plus immunotherapy seems to work very well in many patients.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: Yes. The future is exciting in that regard. In the case of the HPV-positive oropharyngeal cancers, there has also been a lot of interest and push toward robotic surgery in caring for that patient population. I know that that’s not for everybody, and it’s more suited for some of the smaller tumors because of the side effects that might go along with it. What is your understanding of the role of robotic surgery in the care of head and neck cancer patients?

Itzhak Brook, M.D., M.Sc.: Robotic therapy is an amazing new procedure. It’s being done using the robotic tools that are able to do the surgery in a much less invasive way without traumatizing many of the normal tissues of the body. They cause less damage. The recovery period is shorter, and patients benefit from it tremendously. In that procedure, there is a robotic machine that the surgeon operates, and it allows very, very precise ability to cut the cancer out, and it does cause less long-term damage to the tissues and less deformity, you may say. And that’s a wonderful tool. But unfortunately, as you said, it is limited to areas of the body that the robot can reach. And when the cancer is in places that are not reachable by the robotic approach, one needs to use the conventional approach. But even in that area, there is a development of using endoscopic surgery where one can use a laser and the endoscopic approach, or the laser can kill or burn out the cancers that are more deeply located in the throat, again saving major surgery and even saving removal of the larynx from patients.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: That’s right. And also, there’s a push toward de-escalation of the radiation and the chemotherapy in some of these HPV-positive patients, as well, because the tumors are more responsive to the treatment. So, there are many studies going on looking at whether we can do less treatment for the different types of diseases. As you spoke earlier, I think finding the right specialists is important; not everybody is a specialist in all these new and advanced technologies. If you’re looking for robotic surgery, find that specialist that really does a lot of robotic surgery and is an expert in that field. The same is true for the immunotherapy and other treatment approaches as well. So, I think being your own advocate, again, to find these different alternative options and these new treatments in clinical trials becomes exceedingly important in the age of all these new discoveries.

Itzhak Brook, M.D., M.Sc.: Fortunately, the knowledge of experience in those procedures, the laser and the robotic surgery, is becoming more prevalent in the United States. And when I had my cancer, when I needed to make choices 10 years ago, there were only a handful of experts. But right now, almost every major medical center has an expert in those fields, so it’s more available for people.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: Absolutely. So, even if you have to travel a distance to get to those major medical centers, it’s worth the effort and travel and time to be able to seek these other opinions and see what your other options are before pursuing your treatment.

Itzhak Brook, M.D., M.Sc.: Absolutely.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: Yes, I agree.

September, 2018|Oral Cancer News|

Complex cancer decisions, no easy answers

Source: blogs.biomedcentral.com
Author: Jeffrey Liu

With the many different options now available for the treatment of cancer, it can be very difficult for both clinicians and patients to decide on the best possible treatment strategy, particularly when faced with a complicated cancer. In this blog, Dr Jeffrey C. Liu reflects on the challenges encountered in cancer decision making, particularly when presented with difficult cases.

When treating cancer, sometimes the treatment decisions are straightforward and unambiguous. For example, surgery is the treatment of choice for an early, uncomplicated tongue cancer. However, many times, the recommendation for cancer treatment is not straightforward and requires combination treatment – one or more of surgery, radiation or chemotherapy.

As a head and neck cancer surgeon, I work with a team to make these treatment decisions, and usually team consensus is achieved. However, when we are faced with the choice of multiple treatments that all have the same chance of cure available, it seems to result in a never ending discussion amongst our team.

Take for example an advanced tonsil cancer. These cancers can sometimes be removed first with surgery, a process which removes both the primary cancer and the lymph nodes in the neck. Then, depending on the pathology results, patients may need radiation treatment, chemoradiation or sometimes no further treatment at all. Meanwhile, chemoradiation alone, and no surgery, is an excellent option. Whether the patient receives surgery or no surgery, the chance of cure is pretty much the same. However, based on the need for additional treatment after surgery, the patient may have better, equivalent, or worse function than chemoradiation alone.

How then can a patient make a decision with imperfect data? I wish I could help my patients better with these complex decisions. Most patients will make this decision only once in their lives. With the increased emphasis on patient autonomy, there is sometimes a feeling to just “present the options and let the patient decide.”

However, when a group of smart experienced doctors who all treat the same cancer, cannot reach an agreement, how is a patient with no experience expected to make the right decision? There is not enough time to explain to patients the observations of hundreds of such decisions and their thousands of outcomes. Some patients are so overwhelmed by the decision, that they just want someone to tell them what to do. Others have so many questions and concerns that they get lost in the details and paralyzed by the process. I don’t know the right answer for such patients.

Unfortunately, there is no option but to choose a treatment strategy and move forward. We all carry the hope that one day, with more research and better understanding, such complex decisions for the treatment of cancer, will become the easy ones.

October, 2017|Oral Cancer News|

Penn surgeons become world’s first to test glowing dye for cancerous lymph nodes

Source: www.phillyvoice.com
Author: Michael Tanenbaum, PhillyVoice Staff

Surgeons at the University of Pennsylvania have achieved a global first with the use of a fluorescent dye that identifies cancerous cells in lymph nodes during head and neck cancer procedures.

The study, led by otorhinolaryngologist Jason G. Newman, seeks to test the effectiveness of intraoperative molecular imaging (IMI), a technique that illuminates tumors to provide real-time surgical guidance.

More than 65,000 Americans will be diagnosed with head and neck cancers in 2017, accounting for approximately 4 percent of all cancers in the United States, according to the National Cancer Institute. About 75 percent of these cancers are caused by tobacco and alcohol use, followed by human papillomavirus (HPV) as a growing source for their development.

Common areas affected by these cancers include the mouth, throat, voice box, sinuses and salivary glands, with typical treatments including a combination of surgery, radiation and chemotherapy.

Lymph nodes, which act as filters for the immune system, are often among the first organs affected by head and neck cancers as they spread or resurface. Initial surgeries may leave microscopic cancerous cells undetected in the lymphoid tissue, heightening the risk that a patient’s condition will return after the procedure.

“By using a dye that makes cancerous cells glow, we get real-time information about which lymph nodes are potentially dangerous and which ones we can leave alone,” Newman said. “That not only helps us remove more cancer from our patients during surgery, it also improves our ability to spare healthy tissue.”

With the aid of a fluorescent dye, surgeons are able to key in on suspicious tissue without removing or damaging otherwise healthy areas. Previously adopted for other disease sites in the lungs and brain, the practice now allows Newman’s team to experiment with indocyanine green (ICG), an FDA-approved contrast agent that responds to blood flow.

Newman explained that since tumor cells retain the dye longer than most other tissues, administering the dye prior to surgery singles out the areas where cancer cells are present.

The current trial at Penn will enable researchers to determine whether ICG is the most suitable dye for head and neck cancers and provide oncologists with a deeper understanding of how cancer spreads in the lymph nodes.

October, 2017|Oral Cancer News|

Magnolia man joins exclusive trial in battle against cancer

Source: www.cantonrep.com
Author: Denise Sautters

Rich Bartlett is looking forward to getting back to his hobbies — woodworking and nature watching — and enjoying a good steak and potato dinner. Until then, though, he is in a fight for his life, one he plans to win.

Bartlett is a cancer patient and the first participant in a clinical trial at University Hospitals Seidman Cancer Center in Cleveland to test the safety of an immunotherapy drug — Pembrolizumab — when added to a regimen of surgery, chemotherapy and radiation therapy.

Back to the beginning
Bartlett went to the dentist in October for a checkup.

“He had a sore in his mouth he thought was an abscess,” explained his wife, Nancy Bartlett, who pointed out that, because radiation and chemo treatments cause the inside of the mouth to burn and blister, it is hard for Bartlett to talk.

“When the dentist looked at his sore, he sent Richard to a specialist in Canton, and in early November, he had a biopsy done. It came back positive for cancer.”

From there, he was referred to Dr. Pierre Lavertu, director of head and neck surgery and oncology at University Hospitals, and Dr. Chad Zender from the otolaryngology department, who did Bartlett’s surgery.

“They let us know it was serious,” said Nancy. “It had gone into the bone and the roof of the mouth, but they were not sure if it had gone into the lymph nodes. By the time we got through that appointment, it was the first part of December and (they) scheduled him for surgery on Dec. 22.”

The cancer tripled in size by then and the surgery lasted 10 hours. Doctors had to remove the tumor, all of the lymph nodes and parts of the jaw and the roof of Bartlett’s mouth.

“They harvested skin from his hand to rebuild the inside of his mouth, and took the veins and arteries and reattached everything through his (right) cheek,” she said. “He could not even have water until February because of the patch. He uses a feeding tube to eat now.”

The tube is temporary until Bartlett heals.

Clinical trial
Just before he started chemo and radiation therapies, the hospital called him about the clinical trial.

The trial is the first to use quadra-modality therapy — or four different types of therapy — against the cancer, according to Dr. Min Yao, the principal investigator.

Yao said Bartlett has squamous cell carcinoma of the oral cavity, with only a 50 percent chance of survival.

“Patients have surgery, then followed by six weeks of radiation and chemotherapy and immunotherapy,” Yao said in an email interview. “That is followed by six more months of immunotherapy, one dose every three weeks.”

Bartlett currently is in the radiation, chemotherapy and immunotherapy part of the study.

“It is too early to tell how he is responding,” said Yao. “His tumor has been resected. After the treatment, we will see them periodically with scans. Cancer often recurs in the first two years after treatment.”

Pembrolizumab originally was developed to activate the body’s immune system in the fight against melanoma. Former president Jimmy Carter was treated with the drug for his brain metastases from melanoma in 2015.

A truck driver by trade, Bartlett will undergo daily fluoride treatments for the rest of his life to protect his teeth.

“We did not realize until we got to Cleveland just how bad this was,” said Nancy. “When you have oral cancer, and they are getting ready to do radiation and chemo, you have to go have your teeth cleaned and examined and get anything done that needs to be done because radiation tends to compromise your blood flow in your mouth. That was a step we didn’t know.”

Although he was shocked to hear the outcome of that sore in his mouth, Bartlett is grateful to be a part of the trial.

“Who wouldn’t feel good about something like this? I mean, you got something that was used on Jimmy Carter, who is recovered and is now making public appearances again,” said Bartlett, who is looking forward to June when hopefully he can start eating again and enjoying his hobbies.

“I am very hopeful about this. The whole thing has been a trial. I have a dentist in Cleveland who said I was going to be in the fight of my life, and I am. I am in a huge fight. The chemotherapy is what has knocked me down the most, but I am very positive about the outcome of this.”

March, 2017|Oral Cancer News|

Imaging method has potential to stratify head and neck cancer patients

Source: www.eurekalert.org
Author: press release

Manchester researchers have identified a potential new way to predict which patients with head and neck cancer may benefit most from chemotherapy.

These patients commonly receive pre-treatment induction chemotherapy, before either surgery or radiotherapy, to reduce the risk of disease spread. However the effectiveness of such treatment is reduced in tumours with poor blood flow.

Previous studies have shown that CT scans can be used to assess tumour blood flow. Now researchers at The University of Manchester and The Christie NHS Foundation Trust – both part of the Manchester Cancer Research Centre – have explored the use of MRI scans in predicting which patients would benefit from induction chemotherapy.

Professor Catharine West, who led the study, said: “It’s also important to identify those patients who are unlikely to respond to induction therapy so that we can skip ahead in the treatment pathway and offer them potentially more effective treatments and hopefully improve their outcome.”

The team used an imaging technique known as dynamic contrast-enhanced MRI (DCE-MRI), where a contrast agent tracer is injected into a patient’s vein whilst they have a series of MRI scans taken. This allows scientists and doctors to investigate the blood flow and vessel structure of a patient’s tumour.

They found that the blood flow of a patient’s tumour before they received induction therapy could predict response to treatment. In a paper recently published in the journal Oral Oncology, the group report that those with high tumour blood flow were more likely to respond.

Jonathan Bernstein, a co-author on the paper, said: “Delivery and effectiveness of chemotherapy appears to be better in tumours with higher blood flow. However, amongst those patients with lower measured tumour blood flow, more work is needed to determine those who will and won’t respond.”

Source: ‘Tumor plasma flow determined by dynamic contrast-enhanced MRI predicts response to induction chemotherapy in head and neck cancer’, Bernstein et al. (2015) Oral Oncology

September, 2015|Oral Cancer News|

Critical Outcome Technologies and MD Anderson Cancer Center to evaluate COTI-2 in treating head and neck cancers

Source: www.marketwatch.com
Author: press release

Critical Outcome Technologies Inc. (“COTI”), the bioinformatics and accelerated drug discovery company, announced today that it recently executed a material transfer agreement (“MTA”) with Dr. Jeffery Myers, MD, PhD, FACS of The University of Texas MD Anderson Cancer Center for the continued evaluation of COTI-2 in the potential treatment of patients with head and neck squamous cell cancer (“HNSCC”).

There are approximately 500,000 new cases worldwide of HNSCC a year, making it the sixth leading cancer in terms of new cases. In the United States, HNSCC is considered to be a rare disease and therefore represents a second “Orphan Disease” opportunity for COTI-2.

If HNSCC is caught at an early stage, current therapies, which include surgery and radiation followed by chemotherapy, can be effective. Unfortunately, HNSCC tumors with p53 mutations tend to be more difficult to treat with such mutations occurring in 30-70% of HNSCC tumors. These mutations are associated with poorer patient outcomes as traditional chemotherapy, using the current first line chemotherapy, cisplatin, is often ineffective. The overall five-year survival rate of patients with HNSCC is 40-50%.

As a small molecule activator of misfolded mutant p53 protein, COTI-2 has demonstrated in preclinical studies its ability to restore p53 function and thus induce cancer cell death for many common p53 mutations. As previously announced, the Company is planning a Phase 1 study in gynecological cancers (ovarian, cervical and endometrial) at MD Anderson with Dr. Gordon Mills and his team and these studies in HNSCC with Dr. Myers will seek to extend the understanding of COTI-2’s ability to treat p53 mutations across multiple cancer types.

Dr. Jeffrey Myers, leader of MD Anderson’s Multi-Disciplinary Head and Neck Cancer Research Program, has been studying the impact of p53 mutation, a common event in HNSCC, on tumor progression and response to therapy. His group has evaluated a number of single agent and combination treatments for p53 mutant tumors, and his preliminary findings with single agent COTI-2 in HNSCC in vitro tumor models show tremendous promise. In addition to seeing sensitivity of HNSCC cells to COTI-2, his group has found that this drug sensitivity is associated with activation of p21, an important mediator of p53’s response to cellular DNA damage. This response is consistent with the p53-dependent mechanism of action studied by Dr. Mills in ovarian cancer. Dr. Myers and his colleagues are planning more extensive studies of COTI-2 and its dependence on p53 re-activation for its effects in both in vitro and in vivo HNSCC tumor models.

“We look forward to further exploring COTI-2’s impact on HNSCC tumors,” said Dr. Wayne Danter, President and CEO. “We continue to believe that COTI-2 represents a potential breakthrough treatment given the central importance of p53 gene mutations in many cancers, including HNSCC. This second indication would broaden the treatment opportunities for our lead oncology asset, which has already been granted the Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of ovarian cancer.”

October, 2014|Oral Cancer News|

Blood test could predict oral cancer recurrence

Source: www.livescience.com
Author: Rachael Rettner, Senior Writer

A new blood and saliva test that looks for traces of the human papillomavirus (HPV) can predict whether some people with oral cancers will have their cancer come back, early research suggests.

It helps to know as soon as possible that cancer has returned, because tumors that are caught early are easier to treat.

In the study, the researchers analyzed blood and saliva samples from 93 people with head and neck cancers; about 80 percent of these patients had cancers that tested positive for HPV. All of their cancers had previously been treated with surgery, radiation or chemotherapy.

The researchers looked for fragments of DNA from HPV-16, a strain of the virus that is strongly linked with head and neck cancer. The virus may be found in cancer cells that linger in the body after treatment, the researchers said.

Among people with HPV-positive tumors, the new test identified 70 percent of those whose cancer returned within three years, the researchers said.

“Until now, there has been no reliable biological way to identify which patients are at higher risk for recurrence, so these tests should greatly help [to] do so,” study researcher Dr. Joseph Califano, professor of otolaryngology at Johns Hopkins School of Medicine, said in a statement.

Patients with head and neck cancer typically visit the doctor every one to three months during the first year after their diagnoses to check for cancer recurrence. But new tumors in the tonsils, throat and base of the tongue can be difficult to spot, and are often not detected early, the researchers said.

Still, more research is needed to confirm the findings, Califano said. Because HPV infection is common, the test may identify HPV infections that are not related to the cancer. “We can’t be sure our test results are cancer-specific, and not due to other forms of HPV infection or exposure,” Califano said.

The researchers are now looking for additional genetic markers that would increase the accuracy of their test.

Note:
The study is published today in the journal JAMA Otolaryngology–Head & Neck Surgery.

August, 2014|Oral Cancer News|

Researchers find way to diagnose aggressiveness of oral cancer

Source: www.news-medical.net
Author: staff

Studying mouth cancer in mice, researchers have found a way to predict the aggressiveness of similar tumors in people, an early step toward a diagnostic test that could guide treatment, according to researchers at Washington University School of Medicine in St. Louis.

“All patients with advanced head and neck cancer get similar treatments,” said Ravindra Uppaluri, MD, PhD, associate professor of otolaryngology. “We have patients who do well on standard combinations of surgery, radiation and chemotherapy, and patients who don’t do so well. We’re interested in finding out why.”

Reporting in Clinical Cancer ResearchK/em>, the investigators found a consistent pattern of gene expression associated with tumor spreading in mice. Analyzing genetic data from human oral cancer samples, they also found this gene signature in people with aggressive metastatic tumors.

“We didn’t automatically assume this mouse model would be relevant to human oral cancer,” said Uppaluri, who performs head and neck surgeries at Barnes-Jewish Hospital. “But it turns out to be highly reflective of the disease in people.”

Rather than use genetic methods to induce tumors in the mice, the research team repeatedly applied a known carcinogen, in much the same way humans develop cancer of the mouth.

“Patients often have a history of tobacco and alcohol use, which drive the development of these tumors,” Uppaluri said. “We felt that exposing the mice to a carcinogen would be more likely to produce similar kinds of tumors.”

The researchers, including first author Michael D. Onken, PhD, research assistant professor of cell biology and physiology, showed that this exposure sometimes produced tumors in the mice that did not spread, but other times resulted in aggressive metastatic tumors, similar to the variety of tumors seen in people. Uppaluri’s team then collaborated with Elaine Mardis, PhD, co-director of The Genome Institute at Washington University, to find out whether the mouse and human tumors also were genetically similar. They compared their mouse sequences to human data sets from The Cancer Genome Atlas (TCGA).

“When we sequenced these tumors, we found that a lot of the genetic mutations present in the mouse tumors also were found in human head and neck cancers,” Uppaluri said.

Further analysis identified a common signature in the expression of about 120 genes that was associated with the more aggressive tumors, whether in mice or people. The researchers confirmed this signature using data collected from 324 human patients. Subsequently, using oral cancer samples from patients treated at Washington University, they developed a proof of concept test from their signature that identified the aggressive tumors with about 93 percent accuracy.

Working with the Washington University Office of Technology Management, Uppaluri has a patent pending on this technology and recently received funding from the Siteman Cancer Frontier Fund to develop a laboratory test that predicts aggressive disease and would be easily available for any patient diagnosed with head and neck cancer.

“These kinds of tests are available for other types of cancer, most notably breast cancer,” he said. “They are transformative genetic tests that can alter the clinical management of patients, tailoring therapies especially for them. It’s our goal to develop something like that for head and neck cancer.”

Source:
Washington University School of Medicine