EGFR – Oral Cancer News

Clinical trial gets oral cancer survivor through ‘mean’ cancer

Source: web.musc.edu Author: Leslie Cantu Brittany Person was reluctant to enroll in the clinical trial that her oncologist, John Kaczmar, M.D., recommended. Not because she was afraid of taking part in research, but because she just couldn’t deal with any more side effects. She'd already had every one in the book after being treated for a tongue cancer that had returned – and then returned again. “I was just coming off the tail end of chemo, where I had the worst side effects from the chemo and radiation. My body was just tired and beat up and scarred,” she said. When Kaczmar outlined the potential side effects of the investigational drug, she thought, “I just really don't want to do that again. That didn't sound like something I wanted to put myself through.” As she and her husband, Patrick Wilkin, drove from MUSC Hollings Cancer Center to Duke Cancer Institute for a second opinion, Person told Wilkin, “They need to tell me something crazy in order for me to do this trial.” That’s pretty much what they did. “The lady at Duke told me if I didn’t do anything, I would have six months to live,” Person said. “When we got the whole ‘six months to live’ talk, if you do nothing, or two years, if you do the standard immunotherapy, and that the experimental trial is your best shot at actually beating the thing, that's when Brittany and I were like, ‘Yeah, let's do this experimental trial,’” Wilkin said. [...]

Oral Cancer Foundation News Team - A2023-12-15T07:49:56-07:00December, 2023|Oral Cancer News|

Dr Jennifer Choe discusses head and neck dancer relapse, new treatment trials, promising responses

Source: www.ajmc.com Author: Brooke McCormick Jennifer Choe, MD, PhD, shared her thoughts on why head and neck cancer patients relapse after radiation therapy, new head and neck cancer treatment trials, and promising responses from these trials. Choe is a head and neck oncologist at Vanderbilt University Medical Center and was a presenter at The American Journal of Managed Care®’s Institute for Value-Based Medicine® held in Nashville, Tennessee on August 17, 2023. Transcript Can you explain some of the thought behind why there is disease relapse in head and neck cancers after radiation treatment? There's a lot of theoretical basis as to why we think this is the case. A lot is driven by just aggressive biology; it's really not known. Head and neck cancers are considered immune responsive, technically speaking, but the response rates still are pretty low, in general, and whether or not the immune system and head and neck cancer patients are depressed compared to other cancers. I, in theory, think that a part of it is actually the radiation creating an environment where there could be a reduction in the body's ability to regulate the immune system. There's an immune suppressed state for these patients that could be due to radiation of the lymph nodes that's decreasing the ability for the immune system to respond, but also the local radiation induced immune suppression effects that may be producing a more conducive environment for the cancer to return. What are some of the trials evaluating new treatment regimens [...]

Oral Cancer Foundation News Team - A2023-09-02T07:41:01-07:00September, 2023|Oral Cancer News|

Gene mutations that contribute to head and neck cancer also provide ‘precision’ treatment targets

Source: www.sciencedaily.com Author: Medical College of Georgia at Augusta University About one-fifth of often deadly head and neck cancers harbor genetic mutations in a pathway that is key to normal cell growth, and scientists report those mutations, which enable abnormal cancer cell growth, can also make the cancer vulnerable. Keys to targeting that vulnerability include individualized genomic analysis to identify a patient's specific mutation, and finding the drugs that directly target it, investigations that should be given more attention in cancer therapy development, they report in a review article in the journal NPJ Genomic Medicine. The MAPK pathway is a "signaling hub" for cells important to the usual development of the head and neck region, and activating key pathway constituents, like the genes MAPK1 and HRAS, is known to drive the growth of a variety of cancers, says Dr. Vivian Wai Yan Lui, molecular pharmacologist and translational scientist at the Georgia Cancer Center and Medical College of Georgia and the paper's corresponding author. But the mutations in the genes in the MAPK pathway that enable tumor growth can also make it sensitive to drug therapy, says Lui. While a lot of discovery is still needed to find more mutations in the MAPK pathway and the drugs that target them, Lui says they are among the most logical treatment targets for this tough-to-treat cancer. As she speaks, she is looking in her lab for drugs that kill head and neck primary tumors from patients, and at the genetics behind how they [...]

Oral Cancer Foundation News Team - A2022-04-29T05:28:58-07:00April, 2022|Oral Cancer News|

Using proteogenomics to improve the treatment of squamous cell carcinoma

Source: blogs.bcm.edu, Baylor College of Medicine Author: Molly Chiu Patients with head and neck squamous cell carcinoma (HNSCC), the sixth most common epithelial cancer worldwide, are treated with surgery, chemotherapy and radiotherapy. In addition, targeted agents, including an EGFR monoclonal antibody (mAb) inhibitor and two programmed cell death protein 1 (PD-1) inhibitors, have been approved by the U.S. Food and Drug Administration for HNSCC treatment, but response rates are moderate. In this study, researchers led by Baylor College of Medicine, Johns Hopkins University and the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigated what new insight proteogenomic analysis might offer into understanding why certain patients respond to certain treatments while other patients do not. They propose that their findings may help better match patients to an appropriate course of treatment in the future. Building a proteogenomic profile The team profiled proteins, phosphosites (a site on a protein associated with phosphorylation) and signaling pathways in 108 human papillomavirus-negative HNSCC tumors in order to understand how genetic aberrations drive tumor behavior and response to therapies. “We found three subtypes of head and neck squamous cell carcinoma, and each subtype may be a good candidate for a different type of therapy – EGFR inhibitors, CDK inhibitors or immunotherapy,” said Dr. Bing Zhang, lead contact of the study and professor in the Lester and Sue Smith Breast Center and the Department of Molecular and Human Genetics at Baylor. “We also identified candidate biomarkers that could be used to match patients to effective [...]

Oral Cancer Foundation News Team - A2021-02-04T21:09:30-07:00February, 2021|Oral Cancer News|

Distinct subtypes and potential treatment options found in analysis of head and neck cancers

Source: www.cancernetwork.com Author: Matthew Fowler Data published in the journal Cancer Cell presented possible new treatment options and elaborated on the contributions of key cancer-associated genes, phosphosites, and signaling pathways in human papillomavirus (HPV)–negative head and neck squamous cell carcinomas (HNSCC).1 The data systematically recorded information regarding the disease, with multi-omic analysis determining 3 distinct subtypes with high potential for treatment with respective available therapeutics. “This study extends our biological understanding of HPV[-negative] HNSCC and generates therapeutic hypotheses that may serve as the basis for future preclinical studies and clinical trials toward molecularly guided precision treatment of this aggressive cancer type,” wrote the investigators.2 The first subtype, called CIN for “chromosome instability”, was determined to have the worst prognosis. It was associated with the larynx, a history of smoking, and increased instability of chromosomes. The research team suggested that this cancer type would respond best to CDK4/6 inhibitor treatment given its relation to aberrations of the CCND1 and CDKN2A genes as well as a high activity of the CDK4 and CDK6 enzymes. The investigators analyzed a number of protein elevations of basal factors in the second subtype discovered, which was in turn called Basal. These represent the most basic proteins necessary for gene transcription activation. The subtype had both high activity in the EGFR signaling pathway and high expression of the AREG and TNFA molecules. This led the investigators to suggest that treatment with monoclonal antibodies targeting EGFR would best treat this subtype. Immune, the final subtype, was discovered among [...]

Oral Cancer Foundation News Team - A2021-02-03T10:49:17-07:00February, 2021|Oral Cancer News|

Docetaxel regimen tops cisplatin in head and neck cancer

Source: www.cancernetwork.com Author: Anna Azvolinsky, PhD A phase II study has demonstrated that combining docetaxel-based chemoradiotherapy and the antibody cetuximab postoperatively in patients with high-risk squamous cell carcinoma of the head and neck led to improved disease-free and overall survival, with no unexpected toxicities. The results of the study were published in the Journal of Clinical Oncology. Two-hundred and thirty-eight stage III and IV patients were randomized to receive radiation therapy (60 Gy) plus cetuximab and either cisplatin (30 mg/m2) or docetaxel (15 mg/m2) once per week as part of the Radiation Therapy Oncology Group (RTOG) 0234 clinical trial. The 2-year overall survival (OS) was 69% in the cisplatin treatment arm and 79% in the docetaxel treatment arm. The 2-year disease-free survival (DFS) was 57% and 66% in the cisplatin and docetaxel arms, respectively. Previously, two large phase III trials, the RTOG 9501 and the European Organisation for Research and Treatment of Cancer (EORTC) 22931 trials, both showed a small but significant survival benefit for postoperative head and neck cancer patients who received adjuvant radiation and chemotherapy concurrently, resulting in the incorporation of cisplatin in an adjuvant regimen for high-risk patients. The drawback was that adding cisplatin to radiation therapy increased toxicity. Many of these patients are not candidates for the combination therapy due to poor performance status, older age, and renal insufficiency. The purpose of the current trial was to test whether combining a molecular therapy such as cetuximab with chemotherapy would improve survival with a better toxicity profile, [...]

Oral Cancer Foundation News Team - A2014-07-19T07:13:12-07:00July, 2014|Oral Cancer News|

Experimental EGFR inhibitor added nothing but rash

Source: www.oncologypractice.com Author: Neil Osterweil, Oncology Report Digital Network The addition of the experimental targeted agent zalutumumab to primary curative chemoradiation for head and neck cancers did not improve locoregional control, disease-specific survival, or overall survival at 3 years of follow-up. The only thing that zalutumumab added to therapy was a skin rash in the large majority of patients who received it, reported Dr. Jens Overgaard, of the department of experimental clinical oncology at Aarhus University, Denmark. Response to zalutumumab, a monoclonal antibody targeted to the epidermal growth factor receptor (EGFR), was not related to tumor human papillomavirus 16 (HPV/p16) status or to chemoradiotherapy, Dr. Overgaard reported at the Multidisciplinary Head and Neck Cancer Symposium. The results of the DAHANCA 19 trial echo those of the RTOG (Radiation Oncology Therapy Group) trial 0522, which found no benefit from the addition of the EGFR inhibitor cetuximab (Erbitux) to accelerated cisplatin-based chemoradiotherapy, said Dr. Paul Harari, an invited discussant from the University of Wisconsin, Madison. "Where I think we have a lot of unanswered questions is acknowledging how little we actually understand about EGFR biology, despite now 40 years of progressive knowledge," Dr. Harari said. "We’re now seeing very clearly in molecular and clinical correlate studies that the more we suppress the EGFR, the more we see collateral overexpression of additional RTKs [receptor tyrosine kinases], including members of the HER family, such as HER-3, that enable an escape mechanism for tumors that become resistant to EGFR inhibition," he said. Dr. Overgaard and [...]

Oral Cancer Foundation News Team - A2014-03-19T07:20:46-07:00March, 2014|Oral Cancer News|

Are combination therapies effective for advanced SCCHN?

Source: Author: DrBicuspid Staff In a recent study, researchers from the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center examined whether the addition of multiple drugs to radiation therapy is superior to the current standard of care therapy with one drug and radiation for locally advanced squamous cell carcinoma of the head and neck (SCCHN). Their data, published in the Journal of Clinical Oncology, suggests that it does not (March 4, 2013). Standard therapy for SCCHN is a combination of the drug cisplatin and radiotherapy. This clinical trial compared this combination to the combination with the addition of a small-molecule inhibitor of the epidermal growth factor receptor (EGFR) erlotinib. For the study, 204 patients with locally advanced SCCHN were recruited between December 2006 and October 2011. Participants were assigned to receive either cisplatin and radiotherapy or the same chemoradiotherapy with erlotinab. EGFR is a therapeutic target for this type of cancer, and at least one other EGFR is approved for multiple uses in treating head and neck cancer, including in combination with radiation. To date, no data have been published on the use of EGFR inhibitors in combination with chemotherapy and radiation. The goal of the current study was to determine if adding EGRF inhibition improved efficacy when combined with standard of care radiation. Unfortunately, the researchers found that the addition of EGRF did not improve clinical response rate or progression-free survival. "There has been great enthusiasm and some confusion about the combinations of chemotherapy and biologic therapy such [...]

Oral Cancer Foundation News Team - A2013-03-12T07:00:53-07:00March, 2013|Oral Cancer News|

New drug combination could prevent head and neck cancer in high-risk patients

Source: www.sciencedaily.com Author: staff A new drug combination shows promise in reducing the risk for patients with advanced oral precancerous lesions to develop squamous cell carcinoma of the head and neck. The results of the study, which included preclinical and clinical analyses, were published in Clinical Cancer Research, a journal of the American Association for Cancer Research. "Squamous cell carcinoma of the head and neck (SCCHN) is the most common type of head and neck cancer," said Dong Moon Shin, M.D., professor of hematology, medical oncology and otolaryngology at Emory University School of Medicine, and director of the Cancer Chemoprevention Program at Winship Cancer Institute at Emory University in Atlanta, Ga. "The survival rate for patients with SCCHN is very poor. An effective prevention approach is desperately needed, especially since we can identify patients who are at extremely high risk: those with advanced oral precancerous lesions." Based on prior research suggesting a role for epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in promoting SCCHN, Shin and colleagues believed combining an EGFR inhibitor and a COX-2 inhibitor could provide an effective chemopreventive approach. They found that the combination of the EGFR inhibitor erlotinib and the COX-2 inhibitor celecoxib was more effective for inhibiting the growth of human SCCHN cell lines compared with either drug alone. In addition, treating mice with the drug combination prior to transplanting them with human SCCHN cells more effectively suppressed cancer cell growth than did pretreating the mice with either drug alone. Based on these preclinical [...]

Oral Cancer Foundation News Team - A2013-02-20T07:38:26-07:00February, 2013|Oral Cancer News|

Scientists find new way to boost cancer drugs

Source: www.drbicuspid.com Author: DrBicuspid Staff Shutting down a specific pathway in cancer cells appears to improve the ability of common drugs to wipe those cells out, according to new research from scientists at Fox Chase Cancer Center (Cancer Discovery, January 2013, Vol. 3:1, pp. 96-111). The new approach appears to enhance the tumor-killing ability of a commonly prescribed class of drugs that includes cetuximab (Erbitux), used to treat head and neck cancers. These drugs work by blocking the activity of the epidermal growth factor receptor (EGFR), which sits on the cell surface and senses cues from the environment, telling cancer cells to grow and divide, according to co-author Igor Astsaturov, MD, PhD, an attending physician in the department of medical oncology at Fox Chase. In 2010, Dr. Astsaturov and his colleagues identified a pathway in the cell that, when blocked, completely suppressed EGFR activity. Interestingly, the pathway consists of a series of enzymes that, when working in concert, synthesize new molecules of cholesterol. Working with cancer cells in the lab, the researchers inactivated a key gene in the cholesterol synthesis pathway, and found the cells became more vulnerable to treatment with cetuximab. The same was true in mice that lacked this particular pathway, according to Dr. Astsaturov. "Most tumors are only moderately sensitive to inhibitors of EGFR, but when these tumors lack an essential gene in the cholesterol pathway, they become exquisitely sensitive to the anti-EGFR drugs," he said. "The cancers literally melt away in mice." The researchers then removed [...]

Oral Cancer Foundation News Team - A2013-01-21T07:05:01-07:00January, 2013|Oral Cancer News|