Senior Staff Writer

Paper argues for more investigation
into RNA/transcriptomic behavior

The buzz surrounding genetics seems to have died down a bit and has been supplanted somewhat by considerations around other features of cell biology, and a recent statement makes the case that beating cancer requires a better understanding of ribonucleic acid and its transcription activity. The statement notes that researchers at the Vancouver Coastal Health Research Institute (Vancouver, Canada) compared the treatment outcomes for 25 prostate cancer patients with the RNA sequence found in their tumors, and the abstract from the article about this study states that the researchers applied "deep RNA-sequencing and matched whole genome sequencing, followed by detailed molecular characterization" from each of the tumors, all said to represent a highly lethal phenotype. The scientists treated ten of the tumors with neo-adjuvant hormone therapy, nine of which "expressed marked evidence of therapy response," while the tenth is said to have "demonstrated early resistance via apparent neuroendocrine transdifferentiation." The researchers noted a substantial amount of inter-tumor heterogeneity, including "unique sets of outlier transcripts in each tumor," but those outlier expressions "converged on druggable cellular pathways associated with cell cycle progression, translational control or immune regulation, suggesting distinct contemporary pathway affinity and a mechanism of tumor stratification." The researchers stated that they observed "hundreds of novel fusion transcripts, including a high frequency of ETS fusions associated with complex genome rearrangements and the disruption of tumor suppressors." They remarked that several tumors expressed "unique but potentially oncogenic non-ETS fusions," which they speculated could contribute to the phenotypes seen in individual tumors, which might be suggestive of disease progression. One ETS-negative tumor displayed "a striking tandem duplication genotype which appears to be highly aggressive and present at low recurrence in ETS-negative prostate cancer, suggestive of a novel molecular subtype." The authors concluded that the occurrence of these atypical genomic and transcriptomic events "offer novel opportunities for personalized oncology and their convergence on key pathways and functions has broad implications for precision medicine." The article is titled "Heterogeneity in the inter-tumor transcriptome of high-risk prostate cancer," and appears in Endocrine-Related Cancer.

Researchers argue quantity of kinases important, too

The quality vs. quantity debate will no doubt go on as long as there is anyone around to debate, but a recent paper appearing in Nature Methods suggests medical science should pay more attention to quantity where cancer-related protein kinases are concerned. The University of Manchester (UM; Manchester, UK) statement explains that researchers there investigated the make-up of more than 200 protein kinases via mass spectrometry, and the rather brief abstract from the article adds that where targeted proteomics is concerned, "it is critical that peptides are not only proteotypic but also accurately represent the level of the protein (quantotypic)." The authors said that this study demonstrates that measuring ratios of proteotypic peptides across biological samples "can be used to empirically identify peptides with good quantotypic properties," which they applied to identification of quantotypic peptides for 21% of the human kinome. UM's Claus Jørgensen said this method "can correctly measure the amount of protein kinases in a sample. It means we can monitor cancer cell behaviour and also how tumors respond to different therapy in cancer patients," he stated. The article is titled, "Systematic evaluation of quantotypic peptides for targeted analysis of the human kinome."

VCU research sees role for p62 block as combo therapy

Cancer research continues to advance into novel ways to treat the diseases in this category, and a recent statement by Virginia Commonwealth University (VCU; Richmond, Virginia) offers insight into a way to employ the p62 protein to aid in treatment. A study that recently found its way into print in Molecular and Cellular Biology spells out how the VCU scientists induced autophagy with obatoclax while also blocking production of p62 with a cyclin-dependant kinase (CDK) inhibitor. The statement notes that several recent experiments of animal models and cultured multiple myeloma cells showed that blocking p62 disrupted autophagy and "killed far more cancer cells than administering the anti-cancer agents alone." The protein Bik is said to be crucial to the success of this therapy thanks to Bik's role in governing apopotosis. Bik usually piles up in cancer cells until it triggers apoptosis, but cancer cells often use p62 to dispose of Bik. However, the statement notes that blocking p62 production "results in an inefficient form of autophagy and the accumulation of Bik eventually causes the cancer cells to undergo apoptosis." VCU's Steven Grant, associate director for translational research, said "our strategy turns autophagy from a protective process into a toxic one, and these results suggest it could increase the effectiveness of a variety of cancer therapies that induce autophagy." Grant said he and his colleagues are also trying to identify additional CDK inhibitors that can be used to disrupt autophagy, the ultimate goal of which is "to translate these findings into a clinical trial to test the therapy in patients with various blood cancers."

Study finds the mighty tomato

wards off prostate cancer

The Attack of the Killer Tomatoes made headlines in 1978 as a horror movie farce, but reality seems to be imitating art, at least according to a recent statement by the University of Bristol (Bristol, UK), which states at the outset that men who eat more than 10 portions of tomatoes each week have an 18% lower risk of developing prostate cancer. A lycopene-driven study at Bristol and two other universities examined the diets of more than 1,800 men aged 50-69 with prostate cancer, comparing them with more than 12,000 cancer-free men, and the anti-oxidant effects of tomatoes and lycopene are thought to be the drivers of this outcome. Vanessa Er or the University of Bristol said the findings "suggest that tomatoes may be important in prostate cancer prevention," but she acknowledged the need for confirmatory efforts, "especially through human trials. Men should still eat a wide variety of fruits and vegetables, maintain a healthy weight and stay active," Er remarked. The study, which appears in Cancer Epidemiology, Biomarkers and Prevention, is said to be the first to develop a prostate cancer dietary index for substances such as selenium, calcium and lycopene that have been linked to prostate cancer.

University medical centers snare $18 million grant

Columbia University Medical Center and NewYork-Presbyterian Hospital (both New York) reported Aug. 27 they had jointly brought in an $18 million, five-year grant toward cancer research, but the joint cancer center operated by the two also won renewal as its status as a cancer center as designated by the National Cancer Institute. Columbia's Lee Goldman said the renewal would "ensure continuity of our current research, patient care, and educational programs as we continue to add leading cancer researchers and clinicians to our extremely talented and dedicated team." Goldman remarked further that clinical and research programs at the Herbert Irving Comprehensive Cancer Center "have grown significantly in the past several years under the leadership of Dr. Stephen Emerson, and this grant recognizes our potential to change the way cancer is diagnosed, treated, and prevented."

Another classification system surfaces

Medical science is looking for ways to categorize the various cancers, and a recent statement by Cancer Research UK (London) and the University of Cambridge (Cambridge, UK) are said to have developed a tool for classifying breast cancer into 10 subtypes. The research, published in Genome Biology, describes the IntClust system, said to use "genomic technology" to craft a classification system that may help eliminate ineffective treatment regimes. The scientists examined nearly 1,000 tumor samples they used to develop the system along with more than 7,500 samples from public databases, and paired those data with genomic and clinical data including data from the Cancer Genome Atlas. They found that IntClust was at least as good at predicting patients' prognosis and response to treatment as existing systems, but IntClust is also said to have identified a previously unnoticed subgroup of tumors in 3% of women who had exhibited poor survival rates. Identifying the genomic signatures for this group could flag up these high risk cancers early, and having the genomic data for these could aid in the investigation of new avenues for treatments for this type of cancer, the statement notes.

Stopping metastasis by halting 'invadopodia'

Modern imaging has opened a new world up to cancer researchers, and a recent statement by the University of Alberta (Edmonton, Canada) and the Lawson Health Research Institute (London, Canada) explains how recent research there has shed light on the "footwork" of some cancers. The research conducted by the two institutes is said to have confirmed that "invadopodia" play a central role in the spread of cancer via a study appearing in Cell Reports, and the results suggest that preventing "these tentacle-like structures from forming can stop the spread of cancer entirely." In the study, the scientists injected fluorescent cancer cells into the bloodstream of test models, and then captured the fate of these cells using high-resolution time-lapse imaging. Results confirmed the cancer cells formed invadopodia to reach out of the bloodstream and into the tissue of the surrounding organs – they essentially formed "tentacles" that enabled the tumor cell to enter the organ. However, through genetic modification or drug treatment, the scientists were able to block the factors needed for invadopodia to form. This effectively stopped all attempts for the cancer to spread. The study findings confirm invadopodia play a key role in the spread of cancer. Most importantly, they suggest an important new target for therapy. If a drug can be developed to prevent invadopodia from forming, it could potentially stop the spread of cancer.

Toward a better stem cell factory

If you think stem cells might be part of the answer to cancer, the Sept. 2 statement by the University of Colorado (Aurora, Colorado) might be encouraging. A team of scientists at the University of Colorado School of Medicine has published in Plos One on a protein developed there with the ability to prompt blood stem cells to multiply without permanent genetic modifications. The statement offers few details, but Taiga Biotechnologies (Aurora, Colorado) is said to be working to set up first-in-human clinical trials for this blood stem cell expansion approach. The clinical applications range from immunodeficiency conditions to Gaucher syndrome, but the statement notes that this approach may prove useful in leukemia, lymphoma, myeloma and other solid tumors.

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