head and neck cancer (HNC) – Oral Cancer News

Enhanced Radiation Sensitivity in HPV-Positive Head and Neck Cancer

Source: American Association for Cancer Research Received February 28, 2013.Revision received April 9, 2013.Accepted April 26, 2013. Abstract Patients with human papillomavirus (HPV+)–associated head and neck cancer (HNC) show significantly improved survival outcome compared with those with HPV-negative (HPV−) tumors. Published data examining this difference offers conflicting results to date. We systematically investigated the radiation sensitivity of all available validated HPV+ HNC cell lines and a series of HPV− HNC cell lines using in vitro and in vivo techniques. HPV+ HNCs exhibited greater intrinsic radiation sensitivity (average SF2 HPV−: 0.59 vs. HPV+: 0.22; P < 0.0001), corresponding with a prolonged G2–M cell-cycle arrest and increased apoptosis following radiation exposure (percent change 0% vs. 85%; P = 0.002). A genome-wide microarray was used to compare gene expression 24 hours following radiation between HPV+ and HPV− cell lines. Multiple genes in TP53 pathway were upregulated in HPV+ cells (Z score 4.90), including a 4.6-fold increase in TP53 (P < 0.0001). Using immortalized human tonsillar epithelial (HTE) cells, increased radiation sensitivity was seen in cell expressing HPV-16 E6 despite the effect of E6 to degrade p53. This suggested that low levels of normally functioning p53 in HPV+ HNC cells could be activated by radiation, leading to cell death. Consistent with this, more complete knockdown of TP53 by siRNA resulted in radiation resistance. These results provide clear evidence, and a supporting mechanism, for increased radiation sensitivity in HPV+ HNC relative to HPV− HNC. This issue is under active investigation in a series of clinical trials attempting [...]

Charlotte Parker2013-08-01T13:59:40-07:00August, 2013|Oral Cancer News|

Leaders in Dentistry: Dr. Ezra Cohen

Source: Dr. Bicuspid By: Donna Domino, Features Editor Date: July 17, 2013 May 21, 2013 — DrBicuspid.com is pleased to present the next installment of Leaders in Dentistry, a series of interviews with researchers, practitioners, and opinion leaders who are influencing the practice of dentistry. We spoke with Ezra Cohen, MD, an associate professor of medicine and the co-director of the head and neck cancer program at the University of Chicago, and the associate director for education at the university’s Comprehensive Cancer Center. Dr. Cohen specializes in head and neck, thyroid, and salivary gland cancers, and is an expert in novel cancer therapies who has conducted extensive research in molecularly targeted agents in the treatment of these cancers. His research interests include discovering how cancers become resistant to existing treatments and overcoming these mechanisms and ways to combine radiotherapy with novel agents. Here Dr. Cohen discusses trends in the incidence, detection, and treatment of oral and head and neck cancers. DrBicuspid.com: What’s the significance of your recent finding that there may be five distinct subgroups of the human papillomavirus (HPV)? Dr. Cohen: The purpose of the research was trying to define molecular subgroups of head and neck cancer (HNC) to inform therapy and outcomes a lot more than we do now as defined by stage and anatomic site. We were taking advantage of a cohort of patients that we treated in a similar fashion at the University of Chicago with a chemotherapy regimen that we commonly use here. The patients [...]

Webmaster2013-07-19T07:48:02-07:00July, 2013|Oral Cancer News|

Enhanced radiation sensitivity in HPV-positive head and neck cancer

Source: http://cancerres.aacrjournals.orgAuthors: Randall J. Kimple1,*,Molly A. Smith1,Grace C Blitzer1,Alexandra D Torres1,Joshua A Martin1,Robert Z. Yang1,Chimera R Peet1,Laurel D. Lorenz2,Kwangok P Nickel3,Aloysius J Klingelhutz4,Paul F Lambert5, andPaul M Harari1 Abstract Patients with human papillomavirus associated (HPV+) head and neck cancer (HNC) demonstrate significantly improved survival outcome compared to those with HPV-negative (HPV-) tumors. Published data examining this difference offers conflicting results to date. We systematically investigated the radiation sensitivity of all available validated HPV+ HNC cell lines and a series of HPV- HNC cell lines using in vitro and in vivo techniques. HPV+ HNCs exhibited greater intrinsic radiation sensitivity (average SF2 HPV- 0.59 vs. HPV+ 0.22, p<0.0001), corresponding with a prolonged G2/M cell cycle arrest and increased apoptosis following radiation exposure (percent change 0% vs. 85%, p=0.002). A genome-wide microarray was used to compare gene-expression 24 hours following radiation between HPV+ and HPV- cell lines. Multiple genes in TP53 pathway were upregulated in HPV+ cells (Z score 4.90), including a 4.6 fold increase in TP53 (p<0.0001). Using immortalized human tonsillar epithelial cells, increased radiation sensitivity was seen in cell expressing HPV-16 E6 despite the effect of E6 to degrade p53. This suggested that low levels of normally functioning p53 in HPV+ HNC cells could be activated by radiation, leading to cell death. Consistent with this, more complete knockdown of TP53 by siRNA resulted in radiation resistance. These results provide clear evidence, and a supporting mechanism, for increased radiation sensitivity in HPV+ HNC relative to HPV- HNC. This issue is under active investigation in [...]

Charlotte Parker2013-06-10T16:15:32-07:00June, 2013|Oral Cancer News|

Reirradiation for Recurrent Head and Neck Cancer

Source: Medscape News Date: November 29, 2012 Abstract Recurrence of head and neck cancer in a previously irradiated volume presents a challenging problem and has poor prognosis. A minority of patients are eligible for the preferred therapy, surgical resection. Systemic therapy is offered to patients with unresectable disease but offers little, if any, chance of cure. Repeat irradiation with systemic therapy is a potentially curative option. One randomized trial and several cooperative group and institutional studies support its use. Long-term disease-free survival has been observed, albeit with the risk of significant, possibly life threatening, late complications. Intensity-modulated radiotherapy has been shown to reduce toxicity and improve disease control. Novel systemic therapies and radiotherapy techniques, including stereotactic body radiotherapy, are under active study. Introduction Radiation therapy plays a central role in the treatment of head and neck cancer (HNC) patients. Within a treatment paradigm of functional organ preservation, evidence-based guidelines recommend radiotherapy for three quarters of all patients with HNC. [1] Both organ-preserving definitive chemoradiotherapy (CRT) and selective postoperative CRT improve locoregional recurrence (LRR) and prolong overall survival (OS). [2,3] Nevertheless, despite improvements, LRR after CRT continues to be a vexing problem for 20–35% of patients. [4–8] Even patients with favorable prognosis human papillomavirus-related HNC [9] have a LRR rate of nearly 15%. [4] Locoregional recurrence is related to a number of different factors. Some tumors are inherently radioresistant. Additionally, as radiation is delivered more precisely with smaller margins, the potential for recurrences related to 'marginal misses' has increased. Ongoing exposure [...]

Charlotte Parker2012-12-05T14:26:22-07:00December, 2012|Oral Cancer News|