epidermal growth factor receptor – Page 2

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|

‘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|

Boehringer Ingelheim will announce preliminary data in the area of head and neck cancer

Source: pr-usa.net Author: press release Boehringer Ingelheim will announce preliminary data in the areas of head and neck cancer and non-small cell lung cancer (NSCLC) for one of the company's investigational compounds, BIBW 2992. These data will be presented at the 2010 Annual Meeting of the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. BIBW 2992 is an orally-administered small molecule under development that irreversibly inhibits the epidermal growth factor receptor (EGFR/HER1) and human epidermal receptor 2 (HER2) tyrosine kinases. BIBW 2992 data in head and neck cancer(1) New data will report preliminary best response analysis for 74/109 patients from an ongoing Phase 2 study of 124 patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN) who did not respond to platinum-containing therapy. In this study, patients were initially randomly assigned to either BIBW 2992 or cetuximab. Twenty-two percent of the 34 patients receiving BIBW 2992 experienced reduction in tumor size (measured as partial response), compared to 13 percent of the 40 patients receiving cetuximab. Preliminary safety analyses revealed diarrhea and skin-related adverse events as the most common adverse events associated with BIBW 2992. "Metastatic head and neck cancer has a very poor prognosis, and patients are in desperate need for new treatment options," says Tanguy Y. Seiwert, M.D., lead investigator of the trial, University of Chicago Medical Center. "These findings, while preliminary, are encouraging and warrant further investigation of BIBW 2992 in head and neck cancer."

Oral Cancer Foundation News Team - A2010-05-23T12:55:48-07:00May, 2010|Oral Cancer News|

Integration of epidermal growth factor receptor inhibitors with preoperative chemoradiation

Source: Clincancerres Author: Annelies Debucquoy1, Jean-Pascal Machiels2, William H. McBride3, and Karin Haustermans1 Corresponding Author: Annelies Debucquoy, Laboratory of Experimental Radiotherapy, Department of Radiation Oncology, CDG Building, Box 815, UH Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. Phone: 32-16-346900; Fax: 32-16-346905; E-mail:[email protected]. Abstract In many different cancer cell types, the epidermal growth factor receptor (EGFR) pathway becomes hyperactivated because of overproduction of the ligand, overproduction of the receptor, or constitutive activation of the receptor. The overproduction of EGFR and its ligands correlates with poor prognosis in several solid tumors such as lung, colon, and ovary. These observations led to the development of EGFR inhibitors for anticancer treatment. In the last few years, promising results have been obtained in several tumor types, with EGFR inhibitors given as monotherapy or in combined treatments. In particular, cetuximab in combination with curative-intent radiotherapy in head and neck cancer increases median survival over radiation alone. Similarly, the same approach might benefit patients with locally advanced rectal cancer. Unfortunately, the first clinical studies combining chemoradiation with cetuximab in rectal cancer gave disappointing results. Translational research suggested that the low response rate observed might have been due to the strong antiproliferative effect of cetuximab that may have compromised the activity of chemotherapeutics that target proliferating cells. This result indicates the need for more translational research to unravel how the molecular mechanisms might be manipulated to optimize the combined treatment regimen and to identify biomarkers that can select those patients who will derive most benefit. Clin Cancer Res; 16(10); OF1–6. ©2010 AACR. [...]

Charlotte Parker2010-05-03T18:01:14-07:00May, 2010|Oral Cancer News|

Genmab to review clinical plans for head and neck cancer candidate after mixed results from phase III trial

Source: www.genengnews.com Author: staff Genmab is reporting that Phase III results of its antibody for head and neck cancer, zalutumumab, showed that the treatment did not increase overall survival enough for it to be statistically significant but did significantly boost progression-free survival. The company says that it is evaluating its development program in this indication in light of this data. Zalutumumab is a human antibody targeting the epidermal growth factor receptor. The Phase III trial evaluated the treatment in 286 patients with recurrent or metastatic squamous cell carcinoma of the head and neck who failed standard platinum-based chemotherapy. Patients were randomized to receive either zalubumuab in combination with best supportive care (BSC) or BSC alone. Data showed that median overall survival in the zalutumumab plus BSC group was 6.7 months compared with 5.2 months for the BSC-only group. Genmab points out that although this represented a 30% improvement, the increase was not sufficient to demonstrate a statistically significant difference in survival. However, patients in the zalutumumab cohort did demonstrate a 61% increase in progression-free survival compared with those in the BSC-only arm. “The progression-free survival data indicates that zalutumumab can provide a benefit to these cancer patients, and we will review with our clinical advisors and the regulatory agencies how to best proceed with this product,” says Lisa N. Drakeman, Ph.D., Genmab CEO. Zalutumumab is also undergoing Phase I/II trials as a treatment for advanced head and neck cancer either in combination with chemo-radiation or in combination with radiotherapy in [...]

Oral Cancer Foundation News Team - A2010-04-18T11:59:25-07:00April, 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|