(Press-News.org) PHILADELPHIA — Drugs that are used in the clinic to treat some forms of breast and kidney cancer and that work by inhibiting the signaling molecule mTORC1 might have utility in treating some of the more than 15 percent of human cancers driven by alterations in the Myc gene, according to data from a preclinical study published in Cancer Discovery, a journal of the American Association for Cancer Research.
"More than 1 million people diagnosed with cancer each year have a tumor driven by alterations in the Myc gene," said Grant A. McArthur, M.D., Ph.D., professor of translational research at the Peter MacCallum Cancer Centre in Melbourne, Australia. "However, it has proven impossible to develop drugs that effectively target Myc.
"One of Myc's functions is to regulate cell growth. Because mTORC1 is also a regulator of cell growth, we hypothesized that inhibiting mTORC1 with the drug everolimus might suppress Myc-driven tumor initiation and growth."
McArthur and his colleagues tested their hypothesis in a mouse model of Myc-driven lymphoma and found that treatment with everolimus provided strong protection against disease: only four of 33 mice treated with everolimus developed lymphoma, while 22 of 34 mice treated with placebo developed the disease.
In addition, treatment with everolimus led to tumor regression and significantly improved survival compared with placebo in mice with established lymphomas. However, all of these mice eventually relapsed as a result of the growth of lymphoma cells resistant to the effects of everolimus.
"These data confirmed our hypothesis that mTORC1 inhibition could suppress Myc-driven tumor initiation and growth," said McArthur. "The surprise was found in how mTORC1 inhibition led to tumor regression. We had expected that it would trigger cancer cells to die by a cellular process known as apoptosis, but we found that this was not the case."
Detailed analysis of the tumors indicated that everolimus caused tumor regression by inducing cellular senescence.
According to McArthur, normal cells protect themselves when cancer-driving genes are switched on is by entering a state called senescence. When cancers develop, they have found ways to overcome this safeguard. "Our data indicate that one way in which cancers bypass senescence, in particular senescence induced by Myc, is through a signaling pathway involving mTORC1," he said.
Resistance to everolimus treatment in mice with established lymphomas was associated with loss of the function of p53, a protein known to help suppress tumor formation and growth.
"The loss of effectiveness of everolimus therapy against lymphoma cells deficient in p53 function has important clinical implications," said McArthur. "Everolimus could be a useful new string to the bow for clinicians treating patients with Myc-driven cancers, in particular B cell lymphomas, but that it would be helpful only to those patients with functional p53."
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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.
For more information about the AACR, visit www.AACR.org.
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Park Ridge, Ill. (December 14, 2012) – It is estimated that 34% of Americans are affected by an increasingly prevalent condition known as metabolic syndrome which is a combination of at least three of the following risk factors: large waistline, high triglycerides, low HDL cholesterol, high blood pressure and elevated blood sugar.(i) These individuals have a variety of risk factors that increase the likelihood of developing diabetes and cardiovascular disease. Decades of mixed messaging regarding dietary cholesterol have led to avoidance of certain foods, such as eggs, ...
Statistics have entered the life sciences and they are here to stay. This science emerged in the XVIII century by the hand of the mathematicians Thomas Bayes and Pierre Simon Laplace and was used by Gregor Mendel to demonstrate his theory on genetic inheritance. Since the 90s with the appearance of large genomic studies, statistics has become a fundamental tool for the analysis and interpretation of biomedical data. "Today it is difficult to find a scientific article in the field of biomedicine that does not include statistical methodology" explains David Rossell, who performed ...
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The symptoms of sleep-disordered breathing ...
Higher rates of schizophrenia in urban areas can be attributed to increased deprivation, increased population density and an increase in inequality within a neighbourhood, new research reveals. The research, led by the University of Cambridge in collaboration with Queen Mary University of London, was published today in the journal Schizophrenia Bulletin.
Dr James Kirkbride, lead author of the study from the University of Cambridge, said: "Although we already know that schizophrenia tends to be elevated in more urban communities, it was unclear why. Our research suggests ...
An employment contract for NHS consultants introduced in 2003 and including a 27 per cent pay rise over three years failed to increase productivity. The findings emerge from a 10-year study of hospital consultant activity, published today by the Journal of the Royal Society of Medicine, which looked at the levels of consultant clinical activity rates between 1999 and 2009. The researchers found that, despite an expectation by the Department of Health that the contract would result in year-on-year productivity gains of 1.5%, consultant activity levels showed a downward trend. ...
Researchers at the University of Gothenburg, Sweden, and the Chalmers University of Technology, Sweden, demonstrate that an altered gut microbiota in humans is associated with symptomatic atherosclerosis and stroke. These findings are presented in a study published in Nature Communications on December 4.
The human body contains ten times more bacterial cells than human cells, most of which are found in the gut. These bacteria contain an enormous number of genes in addition to our host genome, and are collectively known as the gut metagenome.
How does the metagenome ...
PITTSBURGH, Dec. 13, 2012 – University of Pittsburgh Cancer Institute (UPCI) researchers have identified over 125 genetic components in a chemotherapy-resistant, brain tumor-derived cell line, which could offer new hope for drug treatment to destroy the cancer cells.
The results will be reported in the cover story of December's issue of the journal Molecular Cancer Research, to be published Dec. 18 and currently available online.
The potential drug targets were identified after testing more than 5,000 genes derived from glioblastoma multiforme, an aggressive brain ...
This press release is available in German.
Leipzig. Remains of dead bacteria have far greater meaning for soils than previously assumed. Around 40 per cent of the microbial biomass is converted to organic soil components, write researchers from the Helmholtz Centre for Environmental Research (UFZ), the Technische Universität Dresden (Technical University of Dresden) , the University of Stockholm, the Max-Planck-Institut für Entwicklungsbiologie (Max Planck Institute for Developmental Biology) and the Leibniz-Universität Hannover (Leibniz University Hannover) in the ...
This press release is available in German.
All a question of timing: When bushcrickets mate, the male attaches a sticky package, the so-called spermatophore, to the female's abdomen. Alongside the sperm themselves, this 'bridal present' consists of a protein-rich mass that the female eats after mating. It then takes several hours for the sperm to find their way into the female's reproductive tract. But, who decides when that will happen? A study by the Bielefeld biologists Professor Dr. Klaus Reinhold and Dr. Steven Ramm suggests that it is the male who determines the ...
Montréal, December 14, 2012 – Dr. Marie Kmita and her research team at the IRCM contributed to a multidisciplinary research project that identified the mechanism responsible for generating our fingers and toes, and revealed the importance of gene regulation in the transition of fins to limbs during evolution. Their scientific breakthrough is published today in the prestigious scientific journal Science.
By combining genetic studies with mathematical modeling, the scientists provided experimental evidence supporting a theoretical model for pattern formation known as the ...
