siRNA – Oral Cancer News

Chemical changes to peptide siRNA-carrier enhance gene silencing for future cancer drugs

Source: web.musc.edu Author: Caroline Wallace MUSC Hollings Cancer Center researchers are exploring the use of peptide carriers for the delivery of small RNA drugs as a novel treatment for cancer. The team’s recent work, published online March 19 in the Molecular Therapy — Nucleic Acids journal, lays the foundation for developing a clinically relevant peptide carrier RNAi-based drug treatment strategy for human oral cancer. According to the American Cancer Society, the estimated risk of developing oral cancer in the U.S. is 1 in 60 for men and 1 in 140 for women. Cancer therapies face multiple challenges, including off-target side effects and low efficacy. RNAi-based therapeutics have great potential to overcome these specific treatment challenges. Andrew Jakymiw, Ph.D., who is also an associate professor in the Oral Health Sciences Department at MUSC, focuses on the study of RNA interference (RNAi)-based therapies for oral cancer. RNAi is a method of gene silencing that specifically targets, or tags, messenger RNA (mRNA) for degradation. mRNA contains the genetic code needed to make proteins. Small interfering RNA (siRNA) are the pieces of RNA that can bind to specific regions on mRNA that stop proteins from being made. Scientists are figuring out how to use this to target and silence disease-causing genes. Decades of research have shown that certain proteins are overexpressed in cancer and drive cancer cell growth. The goal of the RNAi drug treatment strategy is to “turn off” the proteins that promote cancer development. Jakymiw said that although the principle is biologically [...]

Oral Cancer Foundation News Team - A2021-05-25T14:37:20-07:00May, 2021|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|

RNA molecules may help treat head/neck cancer

Source: www.drbicuspid.com Author: DrBicuspid Staff A nanoparticle drug delivery vehicle for small interfering RNA (ribonucleic acid) molecules (siRNA) shows promise for the treatment of head and neck cancer, according to a study published in the Journal of Controlled Release. Dong Shin, MD, of Emory University and Mark Davis, PhD, of the Nanosystems Biology Cancer Center at the California Institute of Technology had previously developed a nanoparticle that encapsulates a siRNA agent aimed at a protein known as RRM2. For this study they again collaborated to evaluate the effectiveness of these particles in head and neck cancer (JCR February 8, 2012). RRM2, when overexpressed in these tumor types, plays an active role in tumor progression and in the development of drug resistance, the researchers noted. Initial tests on head and neck tumor cells growing in culture showed that this construct was taken up by the tumor cells, and as a result growth of the cells was inhibited substantially. Based on these findings, the researchers tested a siRNA-loaded nanoparticle in a mouse model of human head and neck cancer. One intravenous injection of the drug shut down production of RRM2 for at least 10 days, with the nanoparticle being present in the tumor for three days, they reported. Four injections given over 10 days triggered a substantial amount of tumor cell death and significantly reduced tumor progression. The researchers did not observe any adverse effects or changes in body weight during therapy. In addition, the drug had no effect on RRM2 production [...]

Oral Cancer Foundation News Team - A2012-04-09T18:25:12-07:00April, 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|