Monthly Archives: September 2010

Evidence-based dentistry – detect oral cancers early through dental exams

Source: www.tonguecancer.com
Author: staff

A recent posting on the American Dental Association web site describes an interesting study conducted by a panel convened by the ADA Council on Scientific Affairs, a sub-group of the American Dental Association.

The panel, in conjunction with the ADA Center for Evidence-Based Dentistry (EBD) staff, reviewed five systematic reviews and four clinical studies to determine if dentists could detect oral cancers early through routine dental examination.

The study panel examined four distinct questions in the detection of oral squamous cell carcinomas during routine dental exams:

1. Does routine dental screening reduce the likelihood of potentially malignant lesions on the tongue, cheeks, lips, gums and other parts of the oral cavity?

2. Do specialized treatments help dentists identify potential cancers during routine examinations?

3. Compared to examinations without specialized detection tools, can dentists identify trouble spots or should dentists use these specialized tools for the early detection of squamous cell carcinomas in the mouth?

4. Are there specific groups which benefit more from detailed, dental examinations – groups such as seniors, smokers, men, women and other groups within the larger study group?

According to the panel’s report, “…while oral cancer screenings may detect potentially malignant and malignant lesions, clinicians are urged to remain alert to signs the lesions may become cancerous or early stage cancers while performing routine visual and tactile examinations in all patients, particularly those who use tobacco or consume alcohol heavily.”

It’s been shown that any kind of tobacco use is a cause for potential oral cancers and, when combined with alcohol, people who use tobacco and alcohol in conjunction, are 15 times more likely to be one of the 30,000 men and women diagnosed with tongue cancer or some other form or oral cancer this year.

In plain English, the panel set out to determine if dentists who examine patients for early signs of cancer increased chances of early detection and the conclusion, reported on the ADA web site, is that, indeed, dentists are often in the best position to detect potential cancerous lesions during routine dental examinations.

Dr. Michael Rethman, who undertook the study, stated, “”What’s most important is that this (review) points to the need for more research on the natural history of squamous cell carcinomas in the mouth and the epidemiology of oral cancer.

We still don’t understand the answers to a lot of fundamental questions like the progression of the disease and whether intervention helps. It’s plausible that early diagnosis helps, but we don’t even know that.

There’s an incredible need for more research on this topic,” Dr. Rethman concluded.

What Is Evidence-Based Dentistry?
EBD is a systematic approach to the delivery of dental care involving four main considerations:

  • the evidence of a problem through a visual examination and a tactile examination by the dentist; this may or may not include special procedures designed specifically to detect oral cancer early
  • evidence produced through viable studies undertaken by specialists in a particular medical field, i.e., are the study results solid evidence that can be used by dentists and other dental professionals
  • the clinician’s professional skills and judgment, a clear indication that dentists must remain current on the latest in early oral cancer detection
  • the patient’s needs and preferences, making the patient a partner in deciding the best course of treatment when squamous cell lesions are detected through a dental exam.

No one of these considerations is more or less important in determining the course of treatment that offers the most positive outcomes and, through the engagement of the patient, EBD creates a more effective partnership between medical and dental professionals and patients. The concerns and needs of patients with regard to quality of life are just as important as the up-to-date treatment options recommended by an oncologist (specialist in treatment of cancer) after oral cancer is detected by a dental professional.

EBD also entails a highly-detailed, systematic approach to the review of studies conducted in the field. This, too, provides the “evidence” dental professionals employ in the practice of EBD. These studies, like the one published on the American Dental Association web site, undergo extensive evaluation with an objective analysis of the way studies are conducted and how study results are interpreted.

EBD relies heavily on number crunching, using statistical data to help medical professionals to formulate courses of treatment for their patients. This “numbers-based” approach eliminates professional bias and offers more predictable outcomes based on evidence gathered in the field.

In other words, EBD relies on real-world statistical data to remove some of the “guess work” out of the early diagnosis of cancerous lesions by dentists. A dentist might overlook a lesion as a possible start of a cancer except that the patient fits one or more of the statistical groups most likely to experience oral cancer. Using EBD, the numbers drive the early diagnosis, not the medical or dental professional’s opinion.

A Systematic Review Increases Diagnostic Specifics
In scientific research, systematic reviews by peers are used to determine the quality of the data collected during the study and to identify possible misconceptions or illogical conclusions drawn by researchers based on the information they gather.

This peer review qualifies the information collected and collated by researchers and provides authority to findings when the systematic review synchs up with the data contained in a collection of studies.

  • Do results from similar studies make sense?
  • Is there an identifiable pattern to results across numerous studies?
  • Are the results founded on quality research and scholarship?
  • Can the results lead to logical, evidence-based conclusions, i.e. tobacco is a leading cause of oral cancers. The studies uniformly back up this conclusion, giving this cause of oral cancer more “weight” than less specific evidence.
  • How were study groups selected? Undiagnosed, diagnosed, a combination? Exactly what groups were a part of each study?
  • How can the evidence be best used by the dental or medical professional in making a diagnosis and designing the optimum course of treatment?

The objective of any systematic review is specificity: while the study may be broad in scope, the on-going review by professional peers is designed to focus on narrow questions that may or may not be answered by a particular study. This is the reason a systematic analysis is undertaken. The more researchers and clinicians study data, the more reliable that data becomes.

Talk to Your Dentist
Evidence-based dentistry starts with you – your preferences and practices. You’re the best advocate you have so take a moment to talk to your dentist during your next visit.

Ask questions and be truthful. If you smoke, tell your dental professional (s/he’ll probably know by the discoloration of your teeth). If you consume alcohol, be straightforward. Explain your view of evidence-based dentistry and how important it is to you that your dental professional remain up-to-date on the latest in systematic reviews and on-going research.

Finally, ask your dentist to perform a visual and tactile examination for early signs of squamous cell carcinoma during each visit.

What? You haven’t seen your dentist in a while? Still smoking? Using snuff? Then you aren’t advocating for good oral health. You’ve heard it before: see your dentist twice yearly for a cleaning and a complete examination based on the latest evidence available to these professionals.

It starts with you. It starts with you making that appointment.

It’s time to pick up the phone and the evidence proves it. Make the call. Today.

September, 2010|Oral Cancer News|

When East meets West, cancer patients win

Source: www.healthzone.ca
Author: Nicole Baute

An ancient four-herb formula used in China for 1,800 years might one day be available as a prescription pill to treat side effects caused by cancer chemotherapy, thanks to research from Yale University and a growing international consortium focused on the globalization of Chinese medicine.

Huang Qin Tang (pronounced Hu-ang Chin Tong) is made with peonies, a purple flower called skullcap, licorice and fruit from a buckthorn tree. The Chinese medicine has long been used for diarrhea, nausea, vomiting and cramps, which happen to be side effects associated with certain chemotherapy drugs.

Now research led by Yung-Chi “Tommy” Cheng, the Henry Bronson Professor of Pharmacology at Yale University, suggests a Western version of this ancient medicine may reduce gut damage caused by chemotherapy in colon and rectal cancer patients.

Cheng says a capsule preparation of this formula, called PHY906, inhibits three processes that cause inflammation during chemotherapy and enhances the recovery of damage to tissue.

“This is an example of West meeting East for treatment of cancer,” Cheng said, on the phone from Taiwan.

Cheng, who has equity interest in the Yale-sponsored company that licenses the technology, is focused on getting PHY906 licensed as a prescription drug in the U.S. — not as a supplement or alternative.

A study published in Science Traditional Medicine Wednesday explains how PHY906 restored intestinal damage in mice caused by chemotherapy and also helped trigger the replacement of damaged intestinal stem cells with healthy ones.

The drug is now in preliminary clinical trials in the U.S., and Cheng says early results have been encouraging.

The research is part of a growing effort to understand and Westernize Chinese medicine. Canadian researchers are amongst those on their way to Hong Kong for the 9th annual meeting of the Consortium for Globalization of Chinese Medicine, which begins on Monday. Cheng, who grew up in Taiwan, is chairman of the consortium’s board of directors.

Michael Rieder, the CIHR-GSK Chair in Pharmacology at University of Western Ontario and the university’s representative to the consortium, has been following — and occasionally critiquing — Cheng’s groundbreaking research.

“I’m a classical Western pharmacologist skeptical of a lot of stuff, so I said, ‘I want to see the proof in the pudding,’ ” Rieder said. “And this combination seems to be very effective. It’s been subject to rigorous testing, and it seems to be very useful as an adjunct to therapy for cancer.”

McMaster University will officially join the Consortium for Globalization of Chinese Medicine next week, becoming the second Canadian university involved.

Stephen Sagar, a professor of oncology at McMaster University specializing in radiation oncology, said technology made it possible for Cheng to split the herbs up into their chemical components, which helped him understand the chemicals that make Huang Qin Tang effective while ensuring consistency and quality.

For the past 15 years Sagar and his McMaster University colleague Raimond Wong have been researching Chinese medicine and its potential implications for cancer treatment. They are currently running a cross-North America trial on the effectiveness of acupuncture on treating xerostomia or dry mouth, a common side effect of chemo for head and neck cancers.

Rieder said the consortium’s aim is adjunctive therapy — Chinese medicine and Western science working together.

“The Western medicine is providing the cutting edge in terms of cure and killing disease, but the Chinese medicine is helping the patient tolerate it better and maybe helping the Western medicine work better,” he said.

September, 2010|Oral Cancer News|

Dentists don’t need tools to screen for oral cancer

Source: auburnpub.com
Author: Dr. Michael Keating

A comment from a patient the other day inspired this month’s topic. I had gone down to the room of one of the hygienists on my team to examine a patient at their six-month preventive therapy visit. I sat down and began examining the skin of the face and neck when the patient asked me what exactly I was looking for. It made me think. Maybe our patients don’t know what we are looking for as we dentists examine them. The exam is much more than coming in, picking up a mirror and explorer and checking just the teeth. Each dentist has their own method and technique of performing the exam. Rest assured, this important step is not missed.

So what is it I am looking for? This particular patient that prompted me to discuss oral cancer asked me the question as I was looking along their hairline and lifting back their bangs so I could examine the scalp and forehead. If you were to look at the Skin Cancer Foundation website (www.skincancer.org) you would find that basal cell carcinoma is found mainly on the face, scalp, ears, neck, shoulders and back. Let’s see, four out of six of those are right front and center to me when I go to look at a patient at their recall exam. Sure makes sense for me to check! So for this patient I told them I was looking for any signs of skin cancer, and if there was anything that I thought was suspicious, I would make a referral to my dermatologist colleagues for further study.

My exam next took me inside the mouth. I was looking for various types of cancer in each area of the mouth. I took a gauze square and grasped the tongue as my patient put their tongue out for me. In the mouth, the most common site for a squamous cell carcinoma is along the side and underside of the tongue. The rest of my exam was completed, looking under the tongue, the floor of the mouth, the throat, the roof of the mouth as far back as I could see and the lips, both inside and out.

Let’s talk about oral cancer a bit. The year 2010 is the fifth in a row in which there’s been an increase in the rate of occurrence of oral cancer. That is one scary statistic, especially to us dentists who are the ones who are looking in the oral cavity every day! The other scary statistic is that if oral cancer is detected in the early stages, the survival rate is 80-90 percent. Unfortunately, the majority of oral cancers are found in the late stage, when the death rate is 45 percent and the treatment is very disfiguring. When we dentists complete the oral cancer screening, there are tools at our disposal to make a decision as to whether a lesion needs to be examined further. Items such as a brush biopsy allow us to make faster decisions to refer for biopsy. Any lesion that is present for two weeks without resolution should be considered suspect and worthy of biopsy or referral. We now have further screening devices, including lights and rinses which have proven to be screening tools, but studies have shown they are no more effective than a thorough visual exam.

Oral cancer is such a disfiguring cancer that it behooves every dentist and hygienist to be part of the process to detect it early. As a patient, you can help to prevent oral cancer by eliminating tobacco use, both smoking and spit tobacco, and limiting alcohol use. Be sure to visit your dentist regularly and tell them if there are any sharp areas on teeth, fillings or dentures, as long-term exposure to these can precipitate cells to become irregular. Hopefully we can improve the detection of this cancer.

Dr. Michael K. Keating, DDS, is a dentist in Auburn

September, 2010|Oral Cancer News|

SciClone identifies unique genetic markers associated with patient response to SCV-07 treatment in oral mucositis

Source: www.marketwatch.com
Author: press release

SciClone Pharmaceuticals, Inc. today announced that researchers have identified two unique gene clusters that differentiated subjects who responded to treatment in the Company’s phase 2a proof of concept study of SCV-07 for the prevention of severe oral mucositis (OM; WHO grades 3-4) in patients with advanced head and neck cancer. The Company believes that the discovery of these gene clusters may assist in providing the framework for effectively identifying those patients most likely to respond to SCV-07 in future clinical trials based on their individual genomic profile or gene signature. These findings were presented today in a poster presentation at the 4th American Association for Cancer Research (AACR) International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

As part of the Company’s recently completed phase 2a OM study, researchers collected and analyzed RNA samples from patients prior to and at the completion of the trial’s treatment phase. Results from this gene expression analysis demonstrated the strong association of two specific gene clusters with patient response to SCV-07. Consistent with SCV-07’s activity as a modulator of the immune system, these clusters included genes associated with G-protein coupled receptors, signal transducers, glycoproteins and membrane proteins.

“The identification of these specific genetic markers represents an exciting and potentially powerful development in the clinical advancement of SCV-07 for the treatment of oral mucositis,” said Dr. Stephen T. Sonis, speaking in his role as Chief Medical Officer of Biomodels, LLC. Dr. Sonis is also a Clinical Professor of Oral Medicine at Harvard University, and a senior surgeon at Brigham and Women’s Hospital and the Dana Farber Cancer Institute. “The previously reported findings from SciClone’s phase 2a study suggested a consistent trend favoring patients in the trial’s high dose group, and we now also have potentially critical insight into why this compound may be more likely to produce a response in a particular subset of patients. These new biomarker data should prove valuable in our ongoing research related to SCV-07 and we plan to further investigate this genomic profile and its connection to potential responders in future studies.”

In addition to the gene expression differences, researchers demonstrated that SCV-07 treatment was associated with significant differences in levels of several immune-related cytokines thought to be important in the development of OM. Samples from patients treated with high dose SCV-07 were analyzed, and it was determined that levels of MIF (p < 0.049), MIP-1 beta (p < 0.049) and VEGF (p < 0.015) were found to be significantly higher compared to placebo, whereas levels of IL-1 alpha (p < 0.045) were found to be significantly lower compared to placebo. The patients in the low dose group did not demonstrate these same changes, consistent with the dose effects seen in the clinical study in which the lower dose did not show the same positive response seen in the higher dose treatment arm. The Company believes that the new information regarding cytokine activity may provide additional insight into the fundamental mechanism of action of SCV-07 in the treatment of OM. "This phase 2a proof of concept study has provided significant clinical data to support the safety and potential efficacy of SCV-07, as well as the increasingly important area of biomarker identification," commented Friedhelm Blobel, Ph.D., SciClone's President and Chief Executive Officer. "Importantly, each of these findings will inform our ongoing clinical development of SCV-07 and we look forward to initiating our phase 2b study in patients with OM in late 2010 or early 2011." On May 17, 2010, SciClone announced topline results from the Company's phase 2a proof of concept study of SCV-07 for the prevention of severe OM in patients with advanced head and neck cancer. Based on the findings from the phase 2a study and completed discussions with the U.S. Food and Drug Administration, SciClone is planning to initiate a phase 2b study in late 2010 or early 2011. As compared to the completed phase 2a trial, the phase 2b study design is expected to include higher doses of SCV-07 and be adequately powered to demonstrate statistical significance. Additionally, researchers will continue to investigate the role of specific genetic profiles on patient response to SCV-07, as well as the potential link between cytokine activity and SCV-07's sub-cellular mechanism of action.

September, 2010|Oral Cancer News|

Nuances in the changing epidemiology of head and neck cancer

Source: Cancer Network
Author: Daniel C. Beachler, MHS

Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of malignancies caused by the traditional risk factors of tobacco, alcohol, and poor oral hygiene, as well as more recently identified roles of human papillomavirus (HPV) and Epstein-Barr virus (EBV).[1-3] We commend Kim and colleagues on their comprehensive review of the epidemiology of HNSCC. There has been a clear change in the epidemiology of HNSCC which has further accentuated differences in etiology, survival, and demographics among HNSCC patients. We will discuss several important nuances of this changing epidemiology, including the role of tobacco, race, sexual behavior, and gender, as well as HNSCC in nonsmokers and nondrinkers.

As tobacco use has declined over the past several decades,[4,5] so has the number of cancers caused by tobacco and alcohol.[1,6,7] Continued decline in tobacco use and associated HNSCC is not guaranteed, however; in fact, some recent evidence suggests rates of tobacco use in the US may be stabilizing.[5] In contrast, the incidence of HPV-associated HNSCC has increased over the past several decades,[7] although it is unclear what is driving this change. The increasing incidence of HPV-associated HNSCC could be related to changes in oral sexual practices resulting in more oral HPV infection, or it may be explained by increased persistence and progression due to changes in relevant cofactors.

Kim and colleagues noted in their review that HPV-associated HNSCC largely occurs among nonsmokers and nondrinkers. While it is true that HNSCC patients with HPV-associated disease are more likely to be young, white, and lacking a history of tobacco or alcohol use, compared with HNSCC patients not infected with HPV,[8] it is underappreciated that nonsmokers and nondrinkers constitute less than 20% of HPV-associated HNSCC cases.[8-10] Many HPV-associated HNSCCs occur among current and former tobacco and alcohol users, including some individuals with very heavy usage.[8-10] While the proportion of HNSCC patients who are nonsmoker nondrinkers (NSNDs) is higher among HPV-associated HNSCCs,[10,11] this does not suggest that NSNDs are at increased risk of these cancers, but simply that other types of HNSCC are rarer among NSNDs. Indeed, the proportion of HNSCCs caused by HPV in the general population has also increased as tobacco-related cancers have declined.[12-14] Smokers may actually be at increased risk of HPV-associated cancer, as tobacco use is associated with increased oral HPV prevalence[15,16] and persistence,[17] and increased odds of HPV-associated HNSCC in some[9] but not other[8] case control studies.

In the past few decades, survival rates for many cancers have improved, but overall survival rates for HNSCC have remained low. Worldwide 5-year survival for HNSCC remains below 50%.[18] Kim and colleagues mention the increased incidence and decreased survival of HNSCC among African Americans compared with Caucasians. Indeed, median survival for African-American oropharyngeal cancer patients is less than half that observed for Caucasian patients in the same clinical care setting.[6,19] Preliminary evidence suggests that a lower proportion of HNSCC among African Americans are caused by HPV compared with Caucasians.[8,19] As individuals with HPV-associated HNSCCs have substantially improved survival compared with those who have HPV-unassociated HNSCC,[20] the racial differences in HPV etiology may explain some of the heterogeneity in HNSCC survival rates. It is currently unclear, however, whether racial disparities in HNSCC survival are explained solely by the greater proportion of tobacco-related HPV-negative HNSCC among African Americans or whether additional biologic and environmental disparities contribute to the observed survival differences. Additionally, as patients with HPV-associated HNSCC who use tobacco have poorer survival,[21] they are an important group to target in improving patient outcomes.

HPV-associated HNSCC represents an emerging viral cancer, and it is therefore important to understand the associated risk factors. Kim and colleagues noted that sexual behavior is an important risk factor for HPV-associated HNSCC. While we strongly agree that current evidence suggests transmission from oral sex,[8,22,23] that relationship sometimes leads to a mischaracterization of this disease as always being associated with promiscuous behavior. While oral HPV infection is not as ubiquitous as genital HPV infection,[24] risk factors for acquisition and progression to cancer are not yet well understood. Recent studies suggest that more than half of HPV-associated HNSCC patients have had five or fewer lifetime oral sex partners and approximately half did not perform oral sex before they were 20 years of age[8,22,25,26]; that is, many people with HPV-associated HNSCC do not have a high-risk sexual history.

The incidence of HNSCC is two- or three-fold higher among men than women, and interestingly this difference is observed for HPV-associated HNSCC as well as HPV-unassociated HNSCC.[7-10,27] While gender differences in the incidence of HPV-unassociated HNSCC are likely explained by differing rates of tobacco and alcohol use,[1,4] it is less clear why such a strong gender difference is observed for HPV-associated HNSCC. A recent systematic review found similar oral HPV infection prevalence in healthy men and women, suggesting acquisition rates may be similar.[24] If the higher incidence of HPV infection in men is not explained by acquisition differences, then it may be due to differences in HPV persistence and progression in men vs women. Differences in innate immune response by gender have been suggested,[28,29] but their effect on oral HPV infection has not been explored. Efficacy of the prophylactic HPV vaccines against oral HPV infection is not known. Because most HPV-associated HNSCC occurs in men, if these vaccines are proven effective against oral HPV infection, this would need to be factored into considerations for HPV vaccination policy in men.

—Daniel C. Beachler, MHS

—Gypsyamber D’Souza, PhD, MS, MPH


September, 2010|Oral Cancer News|

SIBLING proteins may predict oral cancer

Source: www.sciencedaily.com
Author: Medical College of Georgia

The presence of certain proteins in premalignant oral lesions may predict oral cancer development, Medical College of Georgia researchers said.

SIBLINGs, or Small Integrin-Binding Ligand N-linked Glycoproteins, are a family of five proteins that help mineralize bone but can also spread cancer. SIBLINGs have been found in cancers including breast, lung, colon and prostate.

“Several years ago we discovered that three SIBLINGs — osteopontin, bone sialoprotein and dentin sialophosphoprotein — were expressed at significantly high levels in oral cancers,” said Dr. Kalu Ogbureke, an oral and maxillofacial pathologist in the MCG School of Dentistry. “Following that discovery, we began to research the potential role of SIBLINGs in oral lesions before they become invasive cancers.”

The study, published online in the journal Cancer, examined 60 archived surgical biopsies of precancerous lesions sent to MCG for diagnosis and the patients’ subsequent health information. Eighty-seven percent of the biopsies were positive for at least one SIBLING protein — which the researchers discovered can be good or bad, depending on the protein. For instance, they found that the protein, dentin sialophosphoprotein, increases oral cancer risk fourfold, while bone sialoprotein significantly decreases the risk.

“The proteins could be used as biomarkers to predict [the potential of a lesion to become cancerous],” said Dr. Ogbureke, the study’s lead author. “That is very significant, because we would then be in a position to modify treatment for the individual patient’s need in the near future.”

Precancerous oral lesions, which can develop in the cheek, tongue, gums and floor and roof of the mouth, are risk factors for oral squamous cell carcinoma, which accounts for over 95 percent of all oral and pharyngeal cancers. Oral cancer, the sixth most common cancer in the world, kills about 8,000 Americans annually, Dr. Ogbureke said.

Treatment has been stymied up to this point because of clinicians’ inability to predict which lesions will become cancerous. Surgery is standard for oral cancer, but treatment methods vary for precancerous lesions.

“When we treat these lesions now, there’s an implied risk of under- or over-treating patients,” Dr. Ogbureke said. “For example, should the entire lesion be surgically removed before we know its potential to become cancer, or should we wait and see if it becomes cancer before intervening?”

Further complicating the matter is that the severity of dysplasia, or abnormal cell growth, in a lesion can be totally unrelated to cancer risk. Some mild dysplasias can turn cancerous quickly while certain severe dysplasias can remain harmless indefinitely. The protein findings, which help eliminate the guesswork in such cases, “are fundamental,” Dr. Ogbureke said. “If we’re able to recognize these lesions early and biopsy them to determine their SIBLING profile, then oral cancer could be preventable and treatable very early.”

Dr. Ogbureke’s next step is to design a multi-center study that incorporates oral cancer risk factors, such as smoking and alcohol consumption, to further investigate their relationship with SIBLING protein expression.

Source:
Medical College of Georgia (2010, March 5). SIBLING proteins may predict oral cancer. ScienceDaily. Retrieved September 21, 2010,

September, 2010|Oral Cancer News|

‘Synthetic lethality’ strategy improves molecularly targeted cancer therapy

Source: www.physorg.com
Author: Fox Chase Cancer Center

Molecularly targeted therapies can reduce tumors rapidly. However, not all tumors respond to the drugs, and even those that do often develop resistance over time. Looking for a way to combat the problem of resistance, researchers at Fox Chase Cancer Center hypothesized that hitting already weakened cancer cells with a second targeted agent could kill them—but only if it was the right second agent.

One well-validated molecular target for anti-cancer drugs is the epidermal growth factor receptor, or EGFR. Using a novel screening approach, investigators in the Fox Chase Developmental Therapeutics Program identified over 60 additional proteins that are necessary for cells to survive in the presence of an EGFR inhibitor. When they simultaneously blocked the EGFR inhibitors and any one of these other proteins, more of the cancer cells died. The researchers say this screening strategy to identify targets for effective combinations of cancer drugs will open the door for future therapies. Already, two clinical trials are under way to test innovative drug combinations suggested by the new tactic.

“We found that knocking out one or the other target doesn’t have a major effect, but knocking out both increases tumor cell death,” says Igor Astsaturov, M.D., Ph.D., an assistant professor and medical oncologist at Fox Chase. Astsaturov led the study, which will be published in the September 21, 2010 issue of Science Signaling.

To identify additional targets that would boost the effectiveness of EGFR inhibitors against cancer, Astsaturov and colleagues screened only proteins that interact directly or indirectly with EGFR. The team mined the literature and built a candidate set of 638 EGFR-interacting proteins. They then used an experimental technique called small inhibitory RNA (siRNA) systematically to block activity of each of the genes in cancer cells that had been treated with an EGFR inhibitor. In doing so, the investigators demonstrated on three clinically relevant examples for which drugs are already available—PRKC, STAT3, and Aurora kinase A—that these proteins were necessary for cell survival in the presence of an EGFR inhibitor.

This two-hit strategy—where neither hit is adequate to kill the cells, but together they are—is called synthetic lethality. Geneticists have used synthetic lethal screens in experiments with model organisms, such as fruit flies and yeast, for decades, but cancer researchers have only recently adopted the approach.

“We knew from model organisms that there was a dense network of genes. Using bioinformatics tools to intelligently mine this network provided us with a rich source of hits,” says Erica A Golemis, Ph.D., professor and co-leader of the Developmental Therapeutics Program at Fox Chase, and senior author on the new study. Golemis is also co-leader of the Keystone Initiative in Head and Neck Cancer at Fox Chase, and notes that EGFR inhibitors are already broadly used in the clinic for cancers affecting the head and neck.

“The most exciting hit is the Aurora kinase,” Golemis says. Several Aurora kinase inhibitors are already being tested in the clinic and thus are available for testing in combination with EGFR inhibitors.

Based on the new data, Hossein Borghaei, D.O., director of the Lung Cancer Risk Assessment Program at Fox Chase is launching a trial testing the EGFR inhibitor erlotinib with an Aurora kinase inhibitor in patients with non-small cell lung cancer. Astsaturov has started testing a drug called vandetanib—which simultaneously inhibits EGFR and RET (another protein in the EGFR-interacting network)—in patients with esophageal cancer.

In addition to providing a rich source of synthetic lethal hits, limiting the siRNA screen to a previously-defined network of interacting proteins had an important impact on the size of the project, according to Golemis. “A full genome siRNA screen is prohibitively expensive for many labs. This approach makes siRNA screens more accessible to smaller labs and academic institutions.”

September, 2010|Oral Cancer News|

Robotic surgery breakthrough helping Valley throat and mouth cancer patients

Source: www.abc15.com
Author: Jodie Heisner

A breakthrough surgery helping those with mouth and throat cancer is being offered by a surgeon right here in the Valley (Mesa, AZ).

“It’s nice when about every few years something comes along that’s really a giant step,” said Dr. Glen Rothman of Banner Desert Medical Center.

That giant step is being taken with small robotic arms and 3-D imaging. The procedure is done without the doctor even touching you.

“Truly the ability to go through the mouth where my hands and my eyes cannot see, with tiny instrumentation and remove tumors in ways that really just did not exist before this technology,” said Dr. Rothman.

The procedure is helping patients with mouth and throat cancers similar to the type Michael Douglas is fighting.

“It is my understanding that he has squamous cell cancer of his tongue base and that is one of the areas where the daVinci robot could really be used,” said Dr. Rothman.

Douglas has opted for chemotherapy and radiation to treat the disease, but for those that choose the surgery with the daVinci robot there are benefits.

Without the robot the surgery involves cutting through the jaw leaving scarring. Typically patients are in the hospital for at least eight days.

“We do it though the mouth with no incisions on the outside. Just a couple days in the hospital, none of those tubes, no external scars and a much faster, easier recovery,” said Dr. Rothman.

It also helps to eliminate many of the facial deformities that often come with treatment for these types of cancer. It’s a breakthrough that goes beyond the operating room.

September, 2010|Oral Cancer News|

GSK European Commission amends licence for Cervarix

By: GlaxoSmithKline

Source: PharmPro

GlaxoSmithKline (GSK) confirmed today that the European Commission has granted Marketing Authorisation to amend the licence for its cervical cancer vaccine, Cervarix®.

The approval from the European Commission is important as it recognises the extent of cervical cancer protection demonstrated by Cervarix®, which was not highlighted by the previous indication. The licence amendment is supported by data from the largest efficacy trial of a cervical cancer vaccine conducted to date, the PATRICIA study, and acknowledges that Cervarix® has shown efficacy beyond HPV 16 and 18, the two virus types contained in the vaccine.

The summary of product characteristics (SPC) for Cervarix® will be updated to include the prevention of precancerous lesions and cervical cancer causally related to certain strains of the human papillomavirus (HPV) and will reflect data showing efficacy against the two vaccine types contained in the vaccine (HPV 16 and 18) and the three next most common cancer-causing virus types (HPV 31, 33 and 45).* Together these five HPV types (16, 18, 31, 33 and 45) account for 80 percent of all cervical cancers.

* Vaccine efficacy is different for each of the HPV types 16, 18, 31, 33 and 45, and varies in different cohorts and endpoints.

GlaxoSmithKline Biologicals (GSK Biologicals), GlaxoSmithKline’s vaccines business, is one of the world’s leading vaccine companies and a leader in innovation. The company is active in vaccine research, development and production with over 30 vaccines approved for marketing and 20 more in development – both in the prophylactic and therapeutic fields

For further information please visit www.gsk.com

Cervarix® is a registered trademark of the GlaxoSmithKline group of companies.

September, 2010|Oral Cancer News|

Medicare expands coverage of tobacco cessation

By Mike Lillis

Source: thehill.com

The Obama administration on Wednesday expanded Medicare to cover more seniors hoping to kick their tobacco habits.

“Most Medicare beneficiaries want to quit their tobacco use,” Health and Human Services Department (HHS) Secretary Kathleen Sebelius said in a statement announcing the move. “Now, [they] can get the help they need.”

Under previous rules, Medicare covered tobacco-related counseling only for beneficiaries already suffering from a tobacco-related disease.

Under the new policy, Medicare will cover as many as two tobacco-cessation counseling tries each year, including as many as four individual sessions per attempt.

The move is the latest in a string of White House efforts to shift the nation’s healthcare system toward prevention, in lieu of simply treating diseases after they’ve developed.

If successful, the new tobacco policy could pay dividends. Of the 46 million Americans estimated to smoke, about 4.5 million are seniors older than 65, HHS says. And nearly 1 million more smokers are younger than 65, but eligible for Medicare benefits.

They aren’t cheap. Tobacco-related diseases are estimated to cost Medicare about $800 billion between 1995 and 2015.

Donald Berwick, head of the Centers for Medicare and Medicaid Services, said the expansion lends seniors valuable help “to avoid the painful — and often deadly — consequences of tobacco use.”

The change affects Medicare Parts A and B — hospital care and physician services — but not Part D, which already covers smoking-cessation drugs for all beneficiaries.

September, 2010|Oral Cancer News|