Keeping you up to date on recent developments in oncology

Researchers at Sandia, UNM eye silica-liposome combo for liver cancer . . . The effort to use liposomes in cancer treatment has fostered a number of innovations, which can also be said of the use of silica nanospheres, but researchers at the Sandia National Laboratories facility in Albuquerque, New Mexico and the University of New Mexico (UNM; also Albuquerque), have crafted a means by which silica cores can carry anticarcinogenic drugs while wrapped in liposomes to attack cancer cells. According to an April 18 statement by Sandia, the research group, whose work appears in the May edition of Nature Materials, have produced silica nanoparticles as small as 50 nanometers in diameter into which they can load multiple anti-carcinogenics, which they have inserted into liposomes treated so as to bind with an affinity 10,000 higher than for non-cancerous cells. The fabrication process used for the silica nanospheres employs aerosolization of an undescribed precursor solution and has been named evaporation-induced self-assembly, but this process can produce silica nanospheres of up to “several microns in diameter,“ according to Sandia's statement. The researchers have focused on nanospheres between 50 and 150 nanometers because of the ease with which the human body circulates particles in this size range, but the ability of carcinogenic liver cells to absorb these “protocells,“ as they're called, is also a factor in size selection. UNM's Jeff Brinker, PhD, the principal investigator of the team that wrote the Nature Materials article, said of this protocell arrangement that “the enormous capacity of the nanoporous core, with its high surface area, combined with the improved targeting of an encapsulating lipid bilayer permits a single 'protocell' loaded with a drug cocktail to kill a drug-resistant cancer cell,“ which Brinker said is “a million-fold increase in efficiency over comparable methods employing liposomes alone ... as drug carriers.“ The silica cores can be loaded with a variety of cytotoxic agents including silencer RNAs, which are drawing increasing interest as a way to induce apoptosis in cancer cells. At this stage, this approach is still an in vivo effort, although tests on rodent models are in the offing. According to Sandia's statement, this technology “may be commercially available in five years.“

Trial examines urinary PSA as a screening tool . . . Serum levels of prostate-specific antigen (PSA) have fed an oscillating controversy over the meaning of this biomarker for prostate cancer, but a trial now underway at several medical centers in the U.S., including Beth Israel Deaconess Medical Center (Boston) will take up the question of whether urinary PSA levels are a more reliable indicator of prostate cancer and whether a patient's cancer requires treatment. According to an April 14 statement at the Deaconess website, the study is backed by a $3.1 million grant from the National Institutes of Health and is “a multi-pronged study“ that includes men who are scheduled for biopsies due to positive results from serum PSA checks as well as men who will be screened for the first time. Martin Sanda, MD, director of the Multidisciplinary Prostate Cancer Program at Deaconess, said doctors “know that PSA screening has flaws, but instead of eschewing prostate cancer screening altogether, our goal is to determine if molecular urine testing can eliminate the pitfalls of PSA screening and thereby allow life-saving benefits of screening to be realized for aggressive variants of prostate cancer without over-treating patients who may best be left untreated.“ He also noted that because of all the back-and-forth over interpretations of serum PSA, “many patients and primary care doctors have thrown the baby out with the bathwater.“ Over a five-year period, more than 2,400 men will enroll in the study, which will compare serum and urinary PSA levels, but there is a community outreach component to this effort as well. The statement indicates that the outreach will especially focus on African-American men, “who appear to develop prostate cancer more frequently, and who are at increased risk of dying from prostate cancer.“

Parents amenable to genetic testing for children . . . Advances in medical technology have offered more information than cures, but while a few might prefer not to know everything that may lay in wait, a survey conducted by the Georgetown University Medical Center (Washington) indicates that parents might be interested in genetic tests of their childrens' susceptibility to disease. According to an April 18 statement at Georgetown's website, parents who are offered gene tests “to predict their risks of common, adult-onset health conditions say they would also test their children.“ The results of the survey appear in the May edition of Pediatrics (the article appears in the April 18 online edition), and the authors of the study point out that these and other findings “should put pediatricians on alert that parents may chose predictive genetic tests for themselves and for their children, and seek guidance from doctors about what to do with the information.“ The results of the survey come at a time when direct-to-consumer gene tests have stirred up a considerable controversy, but one of the team that wrote the paper suggests that at some point, parents will start hearing from testing labs about testing their children. Kenneth Tercyak, PhD, associate professor of oncology and pediatrics at Georgetown's Lombardi Comprehensive Cancer Center, said that such tests “usually don't offer a clean bill of health and can be hard to interpret even in the best scenario,“ often identifying only “incremental risks for many common diseases.“ The news might also “trigger negative reactions among parents and children, and lead to conversations at the pediatrician's office that providers aren't prepared to have,“ Tercyak pointed out. The study is said to be “part of a larger effort by the National Human Genome Research Institute at the National Institutes of Health to assess the public's use of genetic tests,“ but Tercyak said that the parents who were most interested in testing their own DNA “were interested in having their child tested too“ and were indisposed to make a “distinction between the pros and cons of testing for themselves and for their children,“ an assessment driven largely by the idea that more information allows people to take action to ward off diseases. Kirsten Hawkins, MD, an assistant professor of pediatrics at Georgetown, said that at some point, “the results of pediatric genetic tests could better inform these conversations,“ but that in the interim, “encouraging parents and their children to avoid smoking, consume a well-balanced diet, and stay active are good advice for remaining healthy.“

Researchers suggest starvation as a new approach to cancer control . . . Whether the saying is to feed a cold and starve a fever or the other way around, metabolic starvation has not been a prominent strategy in cancer therapy, but researchers at Thomas Jefferson University Medical College (Philadelphia) have happened upon information suggesting that a mechanism that interrupts metabolic processes in cancer cells might at least blunt the disease. According to an April 15 statement at the Jefferson website, patients with cancers that devour large quantities of ketones and lactates for fuel have significantly poorer outcomes than those whose cancers consume less of these fuel sources because these hungrier cancers are also more recurrent and more aggressively metastatic. Hence, the idea that any interference in intra-cellular metabolic mechanisms could tamp down on tumor development. One of the complicating factors is that normal cells that are also busily devouring ketones and lactates demonstrate a high degree of stem cell replication, so any therapies employing this metabolic interruption have to be finely targeted to cancer cells. The research is preliminary and is reported in the April 15th online issue of Cell Cycle, but the investigators, who have dubbed this approach to personalized cancer medicine “metabolo-genomics,“ are nonetheless confident of the utility of this metabolic mechanism. Michael Lisanti, MD, of Jefferson and a member of the Kimmel Cancer Center, said this development can help predict “if a patient is at a high-risk for recurrence or metastasis,“ but he also said that the development “is getting to the heart of personalized cancer medicine. Now, we have identified a panel of biomarkers that directly links cancer metabolism with targeted cancer therapy,“ he said. One idea that the researchers have floated in response to their findings is the use of therapeutics “that target oxidative mitochondrial metabolism, such as the antioxidant metformin,“ a drug that is also used to treat diabetes, the statement indicates. Martinez-Outschoorn, MD, of the department of medical oncology at Jefferson, the lead author of the paper, said “it's not just that we know those patients will have poor survival; we know that those patients are using mitochondrial metabolism, which is the type of energy metabolism that we should be targeting with new anti-cancer drugs.“

– Compiled by Mark McCarty, MDD Washington Editor