DNA repair process may offer important insights . . . A number of cellular processes are proving valuable in the effort to diagnose and treat cancer, and a recent statement by Duke University Medical Center (Durham, North Carolina) states that the process by which cells repair DNA might "identify new prospects for developing cancer therapies." The statement notes that research underway at the Duke Cancer Institute zeroes in on "a complex series of events that cells routinely undertake to repair DNA damaged by" a variety of events, including exposure to the sun and normal metabolic processes, which can damage DNA in ways that can lead to the development of cancer. The abstract from the article in the Proceedings of the National Academy of Sciences states that researchers at Duke have "developed a system that can induce" DNA double-strand breaks (DSBs) "rapidly at defined endogenous sites in mammalian genomes and enables direct assessment of repair and monitoring of protein recruitment, egress, and modification at DSBs." The statement explains further that the system developed at Duke caused DNA breakage "at defined points on the DNA strands," which allowed researchers to track developments in the DNA repair process, noting that this tracking for the first time allowed them to see "a choreographed interaction in which the tightly wound DNA was temporarily loosened" when nucleolin was recruited to the breakage site. The nucleolin is said to have disrupted the nucleosome spool, and the process "was then reversed when the nucleosome was re-formed after repair was complete." Michael Kastan, MD, executive director of the Duke Cancer Institute, remarked, "e never had good assays to measure how DNA breaks are repaired, and there were few good tools to study how that repair unfolds at the molecular level," but he said this work "for the first time enables us to both sensitively measure the repair of DNA breaks and study the molecular mechanisms by which they occur."

Four markers tied to head and neck cancers . . . Researchers at Queen Mary, University of London (London) have been investigating genetic markers that are either over or under-expressed in head and neck cancer and have come up with a list of four suspects that might enable doctors to predict whether a patient is likely to develop one of these diseases. The statement indicates that expression of the four genes – which are not listed in the statement – "was inversely correlated with particular DNA methylation marks, suggesting the genes are epigenetically modified in these cancers." To arrive at the markers of interest, the researchers reviewed clinical specimens of malignant tissue from nearly 100 cancer patients from Norway and the UK, and compared them with "either tissue donated by healthy individuals undergoing wisdom tooth extractions, or with non-cancerous tissue from the same patients." The hope is that the identified epigenetic markers could be used to screen for head and neck cancer, but this is a preliminary effort and has not yet been deployed as a diagnostic. These findings appear in the journal Cancer.

Article argues for protons for pediatric patients . . . The flap over costs associated with proton beam therapy shows no signs of fading, but a recent statement by Penn Medicine (Philadelphia) throws a new twist into the discussion by arguing that radiation dose reduction associated with proton beam therapy is an important consideration for children. A study to be presented at the 55th annual meeting of the American Society for Radiation Oncology (ASTRO; Fairfax, Virginia) conference followed 25 patients aged 1-21 years shows that after a mean of 13 months of treatment, 19 of which (76%) exhibited "no evidence of disease" while another three patients had developed a local recurrence. Another five were diagnosed with stable tumors while one patient died. These outcomes "are generally equivalent to those that would be expected with more traditional X-ray therapy," the statement acknowledges, but the difference was "the greatly reduced side effects observed in the study, compared to the prevalence seen among head and neck cancer patients undergoing X-ray treatment." The study's lead author, Christine Hill-Kayser, MD, an assistant professor of radiation oncology at Penn Medicine, said "our findings using proton therapy for these patients ... show that side effects are milder than those which are typically seen among children undergoing conventional radiation. We hope that this will translate to mean fewer late effects as they survive their cancer," she said. The statement also notes that by three months, all the study patients had fully recovered from any acute side effects incurred during proton treatment. Hill-Kayser said she believes the study will bolster the increasing perception that "pediatrics is one of the areas where proton therapy is going to provide a lot of benefit."

U of Utah snares more NIH money for melanoma . . . Tax dollars continue to pour into academic research for cancer, and a recent statement notes that the University of Utah (UofU; Salt Lake City) picked up a grant of $1.5 million to investigate the role of the c-KIT gene in the origin and growth of melanoma. The statement reminds that most melanomas are associated with mutations in the BRAF gene, but that mutations in c-KIT "have already been identified as the most common cancer-causing event in certain melanoma subtypes that rarely harbor BRAF mutations." Among these is a melanoma caused by chronic damage from solar exposure. Some clinical trials have shown good response to drugs targted at c-KIT, but resistance ordinarily develops, hence the need for a different approach. UofU's Matt VanBrocklin, PhD, is credited with developing "a novel melanoma mouse model that will allow deeper examination of c-KIT's role in melanoma's initiation and progression," and VanBrocklin will use the five-year grant to establish whether c-KIT "can initiate melanoma," although he will also "examine other genetic factors that could enhance c-KIT's action," according to the statement.

Zevacor eyes cyclotron for isotopes . . . The medical isotope dilemma in the U.S. and other nations is nudging companies off the sidelines, including Zevacor Molecular (Indianapolis), which announced Sept. 25 that its board of directors has approved funding for the purchase of a cyclotron "dedicated to medical use." The statement notes that Zevacor has in mind a 70 million electron volt commercial cyclotron, which would the largest commercial cyclotron for this use, and the company indicates it should have an awardee to announce within 30 days of the Sept. 25 statement. The company indicates that it intends to have the cyclotron ready to go by 2016. Zevacor's chief operating officer John Zehner said that of late, "the supply of medical isotopes has not been continuous, making it difficult to offer these diagnostics and therapeutics." He noted that the company's investment "will allow us to provide year round production of medically necessary isotopes for patients."

Petten reactor stays offline after maintenance stoppage . . . The high-flux reactor operated by the Netherlands government's Nuclear Research Group was recently shut down for maintenance, but operators are not bringing the reactor back online immediately due to "an abnormality in one of the [reactor's] six control rods." The Oct. 1 NRG statement offers little more on the matter than to state that staff will investigate "the cause of this abnormality," and that the reactor will not resume operations until the problem is resolved. The reactor was commissioned in 1961 and was designed to run until 2015. The Dutch government is sponsoring the development of a replacement reactor, the Pallas high-flux reactor, a half-billion dollar project expected to go live in 2023.

— Compiled by Mark McCarty, MDD Washington Editor

mark.mccarty@thomsonreuters.com

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