EGFR – Page 2 – Oral Cancer News

Head and neck cancer presentation highlights

Source: www.dailyrx.com Author: Travis Giddings The field of head and neck cancer from ASCO 2012 A recent presentation at the American Society of Clinical Oncology expanded on several molecular breakthroughs concerning head and neck cancers, and a team of doctors gave an overview of recent conclusions from their respective fields. The newly identified molecular pathway for cancers of the head and neck that involves the epidermal growth factor receptor (EGFR) led to developments of highly effective drugs specific for the cancerous cells, EGFR inhibitors. Soon afterwards, scientists discovered the increasingly important role that the human papillomavirus (HPV) played in the development of cancers in the head and neck. Following the explosion of research in the field of molecular pathways involved in head and neck cancers, doctors quickly found that the cancer was a lot more complicated than previous believed. Additional research continues as scientists try to make sense of the data. Approaching the treatment of head and neck cancer from their perspectives from surgery, radiology, and oncology, doctors on the panel discussed the difficulties the field currently faced. The director of Johns Hopkins' Head and Neck Cancer Research department, oncologist David Sidransky, MD, opened the meeting. “The genetic and epigenetic alterations in human tumors are becoming increasingly important for devising and implementing personalized oncology approaches,” said Dr. Sidransky. “Unlike in some other cancers, in head and neck cancer the common mutations that have been identified have not been very helpful for treatment.” The chair of the conference was held by [...]

Oral Cancer Foundation News Team - A2012-06-08T07:56:18-07:00June, 2012|Oral Cancer News|

Erlotinib dose doubled for smokers with head/neck cancer

Source: www.oncologyreport.com Author: Miriam E. Tucker Giving smokers a higher, short-course dose of erlotinib before definitive surgery for squamous cell carcinoma of the head and neck resulted in favorable responses for the first patients evaluated in a small pilot study. Investigators gave 300 mg of erlotinib (Tarceva) to smokers daily and 150 mg daily to nonsmokers who had a waiting period of more than 14 days before scheduled surgery for head and neck cancer. Seven of the 10 patients evaluated so far had partial responses and 3 had stable disease, according to a poster presented at a head and neck cancer symposium sponsored by the American Society for Radiation Oncology. The study was based on recent data in non–small cell lung cancer (NSCLC) patients showing that smokers metabolize erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, twice as quickly as do nonsmokers (J. Clin. Oncol. 2009;27:1220-6), said lead author Dr. Mercedes Porosnicu of Wake Forest Baptist Medical Center in Winston Salem, N.C. That study established the maximum tolerated dose of erlotinib at 300 mg daily in NSCLC patients who smoke. Dr. Poroniscu’s presentation included the case study of a smoker with a very large oral cavity tumor protruding through his lips. He was described as being in significant pain and unable to eat or chew. The first CT scan showed a tumor of at least 8 cm and there was "significant metabolic activity" on PET scan. "At 6 days of erlotinib treatment, his tumor was obviously smaller and he could [...]

Oral Cancer Foundation News Team - A2012-01-28T08:25:19-07:00January, 2012|Oral Cancer News|

Roche scientist provides a look at drugmaker’s early pipeline

Source: www.nj.com/ Author: Susan Todd/The Star-Ledger Jean-Jacques Garaud, who heads Roche’s pharmaceutical research and early development efforts in Switzerland, visited the drugmaker’s Nutley campus in mid-December and spent some time speaking with The Star-Ledger about the company’s efforts in the laboratory. The talk with Garaud provided a rare glimpse of the giant Swiss drugmaker’s early-stage pipeline and highlighted the heavy bets it’s making on personalized medicine (drugs that are tailored to treat individuals whose genes or enzymes show specific biological signs of disease). If the strategy succeeds, Roche could eventually push out some breakthrough drugs for cancer, Alzheimer’s disease and depression. Garaud, a French-American who joined Roche five years ago, also opened up about a discovery made in Nutley that may represent a novel cancer treatment and the high hopes behind a project with the promise of altering the lives of individuals born with a syndrome that causes mental retardation. During the interview, Garaud talked about some medicines so early in development that they are still referred to by strange-sounding laboratory names. Q. Where do things stand with gantenerumab, the monoclonal antibody Roche is developing as a treatment for Alzheimer’s disease? A. This is in phase 2 and this is testing a patient population in the early stages of the disease or suffering from mild cognitive impairment. We believe this particular type of intervention may be more beneficial when it happens early in the disease so that it delays progression. This antibody targets the abnormal material called amyloid that deposits [...]

Oral Cancer Foundation News Team - A2012-01-02T06:41:44-07:00January, 2012|Oral Cancer News|

Yale School of Medicine Researchers take a closer look at “smart drugs”

Source: Yale University Some of the most effective and expensive cancer drugs, dubbed "smart drugs" for their ability to stop tumors by targeting key drivers of cancer cell growth, are not effective in some patients. In two related studies, Yale School of Medicine researchers examined one such driver, the EGF receptor (EGFR), and found that a decoy receptor might be limiting the amount of drug that gets to the intended target. "We know that smart drugs like Cetuximab are not always effective in the cancer cells they're supposed to target because there are no positive predictive markers for selecting the patients who will benefit from treatment with EGFR-targeted therapies, including EGFR itself," said lead author Nita Maihle, professor in the Departments of Obstetrics, Gynecology & Reproductive Sciences and of Pathology at Yale School of Medicine. "Why would a patient be given an expensive drug if it doesn't work? Our studies provide new insight into this paradoxical EGFR testing conundrum." In a study published recently in the journal Cancer, Maihle and her team isolated a protein from human blood that looks like EGFR, but is actually a closely related variant called serum sEGFR. They showed that Cetuximab binds equally as well to serum sEGFR as it does to the intended EGFR cancer target. Those study results showed that sEGFR might act as a decoy receptor in the blood of cancer patients, tying up Cetuximab and therefore limiting the amount of Cetuximab that actually gets to the intended target. Such limitations may, [...]

Oral Cancer Foundation News Team - A2011-05-19T13:43:34-07:00May, 2011|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 [...]

Oral Cancer Foundation News Team - A2010-09-21T12:40:30-07:00September, 2010|Oral Cancer News|

ASCO: Antibody improves head and neck cancer results

Source: www.medpagetoday.com Author: Michael Smith, North American Correspondent, MedPage Today A novel antibody improved outcomes for patients with advanced and inoperable squamous cell carcinoma of the head and neck, researchers reported. Combined with radiation or chemoradiation, the substance -- a fully humanized monoclonal antibody dubbed nimotuzumab -- significantly outperformed either modality alone in an open-label randomized trial, according to K. Govind Babu, MD, of Kidwai Memorial Institute of Oncology in Bangalore, India, and colleagues. At the same time, there was little serious toxicity -- such as debilitating skin rash -- attributed to the compound, the researchers reported in a poster discussion session at the annual meeting of the American Society of Clinical Oncology here. It's the first randomized study of the drug to show clinical benefit without the toxicities associated with similar antibodies, the researchers said. In general, neither radiation nor chemotherapy provides a good outcome for patients with inoperable stage III or IVa squamous cell carcinoma of the head and neck. However, substances such as cetuximab (Erbitux) that target the epidermal growth factor receptor (EGFR) -- overexpressed in such tumors -- have improved outcomes. Nimotuzumab, like cetuximab, targets EGFR, but is highly selective for tumor tissues, limiting toxicity, the researchers said. The study enrolled 92 patients, and 76 were evaluable for efficacy. They were treated with radiation or chemoradiation (with cisplatin), with or without nimotuzumab. The substance was given by intravenous infusion of 200 milligrams over a 60-minute period, once a week for six weeks. In group A -- [...]

Oral Cancer Foundation News Team - A2010-06-06T07:24:13-07:00June, 2010|Oral Cancer News|

Nano-bio-chip sensor platform for examination of oral exfoliative cytology

Source: Cancer Prevention Research 3(4); 518-28, March 23, 2010 Authors: SE Weigum et al. Oral cancer is a deadly and disfiguring disease that could greatly benefit from new diagnostic approaches enabling early detection. In this pilot study, we describe a nano-bio-chip (NBC) sensor technique for analysis of oral cancer biomarkers in exfoliative cytology specimens, targeting both biochemical and morphologic changes associated with early oral tumorigenesis. Here, oral lesions from 41 dental patients, along with normal epithelium from 11 healthy volunteers, were sampled using a noninvasive brush biopsy technique. Specimens were enriched, immunolabeled, and imaged in the NBC sensor according to previously established assays for the epidermal growth factor receptor (EGFR) biomarker and cytomorphometry. A total of 51 measurement parameters were extracted using custom image analysis macros, including EGFR labeling intensity, cell and nuclear size, and the nuclear-to-cytoplasmic ratio. Four key parameters were significantly elevated in both dysplastic and malignant lesions relative to healthy oral epithelium, including the nuclear area and diameter (P

Oral Cancer Foundation News Team - A2010-04-04T09:12:06-07:00April, 2010|Oral Cancer News|

Epidermal growth factor receptor regulates beta-catenin location, stability, and transcriptional activity in oral cancer

Source: 7thspace.com/headlines Author: staff Many cancerous cells accumulate beta-catenin in the nucleus. We examined the role of epidermal growth factor receptor (EGFR) signaling in the accumulation of beta-catenin in the nuclei of oral cancer cells. Results: We used two strains of cultured oral cancer cells, one with reduced EGFR expression (OECM1 cells) and one with elevated EGFR expression (SAS cells), and measured downstream effects, such as phosphorylation of beta-catenin and GSK-3beta, association of beta-catenin with E-cadherin, and target gene regulation. We also studied the expression of EGFR, beta-catenin, and cyclin D1 in 112 samples of oral cancer by immunostaining. Activation of EGFR signaling increased the amount of beta-catenin in the nucleus and decreased the amount in the membranes. EGF treatment increased phosphorylation ofbeta-catenin (tyrosine) and GSK-3beta(Ser-9), resulting in a loss of beta-catenin association with E-cadherin. TOP-FLASH and FOP-FLASH reporter assays demonstrated that the EGFR signal regulates beta-catenin transcriptional activity and mediates cyclin D1 expression. Chromatin immunoprecipitation experiments indicated that the EGFR signal affects chromatin architecture at the regulatory element of cyclin D1, and that the CBP, HDAC1, and Suv39h1 histone/chromatin remodeling complex is involved in this process. Immunostaining showed a significant association between EGFR expression and aberrant accumulation of beta-catenin in oral cancer. Conclusions: EGFR signaling regulates beta-catenin localization and stability, target gene expression, and tumor progression in oral cancer. Moreover, our data suggest that aberrant accumulation of beta-catenin under EGFR activation is a malignancy marker of oral cancer. Author: Chien-Hsing LeeHsing-Wen HungPei-Hsin HungYi-Shing Shieh Source: Molecular Cancer 2010, 9:64

Oral Cancer Foundation News Team - A2010-03-22T08:59:51-07:00March, 2010|Oral Cancer News|

New DNA therapy for advanced mouth cancer

Source: www.dentistry.co.uk Author: staff A research team has been awarded a patent after developing a new DNA therapy for head and neck cancer sufferers. Researchers from the University of Pittsburgh School of Medicine in the US, aims to develop a safe and effective alternative to standard chemotherapy treatments which cause debilitating side-effects. Based on a form of genetic therapy called ‘antisense', the new DNA therapy injections target the epidermal growth factor receptor (EGFR), blocking the growth of a protein which is found on the surface of many types of cancer cells. During the initial Cancer Institute study, led by Dr Jennifer Grandis, the injections were well-tolerated, and the tumours which were being targeted by the treatment disappeared or shrank considerably in more than a quarter of the patients. The British Dental Health Foundation has welcomed the latest development in treating this deadly disease. Chief executive Dr Nigel Carter said: 'These new findings show that this new DNA therapy can have the potential as both a safe and effective advanced cancer treatment. One of the major problems with mouth cancer is that it often presents in late stages, significantly reducing survival – so a late stage treatment is particularly welcome. 'Head and neck cancers have a strong association with environmental and lifestyle risk factors including smoking tobacco, alcohol consumption and the sexually transmitted human papilloma virus (HPV). 'Research has recently suggested that the HPV virus, transmitted via oral sex, could soon become the most common cause of mouth cancer.' Cancers caused [...]

Oral Cancer Foundation News Team - A2010-02-07T09:42:31-07:00February, 2010|Oral Cancer News|

Pitt researchers receive patent for new head and neck cancer treatment

Source: www.healthcanal.com Author: staff Researchers from the University of Pittsburgh School of Medicine have been awarded a patent from the U.S. Patent and Trademark Office for the development of a new DNA therapy for head and neck cancers. The therapy targets the epidermal growth factor receptor (EGFR), a protein found on the surface of many types of cancer cells that causes them to multiply. Standard treatments for head and neck cancers often are ineffective and tend to have debilitating side effects, explained Jennifer R. Grandis, M.D., professor of otolaryngology and pharmacology at Pitt and director of the Head and Neck Program at the University of Pittsburgh Cancer Institute (UPCI). “We set out to develop an alternative approach that is safe and effective for these cancers,” she said. The new treatment is based on a form of genetic therapy called “antisense,” or AS, in which a synthesized strand of DNA or RNA targets the EGFR genes within a head and neck tumor. The therapy blocks the production of a protein produced by the gene. According to Dr. Grandis, expectations were exceeded in a phase I study of the therapy that was designed primarily to determine the safety and potential toxicity of EGFR AS injections in patients with advanced head and neck cancers. “Not only were the AS injections well-tolerated, but tumors disappeared or shrank considerably in 29 percent of the patients,” said Dr. Grandis. “These results show that EGFR AS therapy has great potential as a safe, effective treatment.” A phase [...]

Oral Cancer Foundation News Team - A2010-01-31T06:34:56-07:00January, 2010|Oral Cancer News|