The knowledge on the molecular bases of cancer generated during the last decades has been successfully translated into small but significant gains in overall cancer survival rates due to better primary prevention measures, improved diagnostic methods and the development of more effective and specific therapies, collectively termed “molecular targeted therapies”. In the context of these new forms of treatment, epigenetic or transcriptional cancer therapy is clearly promising.
Epigenetics refers to the function of DNA that does not depend on the coding DNA sequence itself but on the accessory molecules and mechanisms affected by DNA. It is known that epigenetic alterations are equally if not more important than classical genetic alterations to disrupt the function of tumour suppressor genes. The two most studied epigenetic aberrations common to all types of cancer are DNA hypermethylation and histone deacetylation, which cooperate to silence the expression of tumour suppressor genes, just as gene mutations and gene deletions do. The big difference between these two alternative ways that tumour cells use to inactivate tumour suppressor genes is that, while the reversal of genetic alterations is technically almost unfeasible in clinical scenarios, the function of these epigenetically inactivated suppressor genes is easily reactivated by pharmacological means. In this inaugural issue of PLoS ONE, Dr Dueñas-Gonzalez’s group from the Instituto de Investi gaciones Biomédicas of the Universidad Nacional Autónoma de México and the Instituto Nacional de Cancerología, Mexico, demonstrate, for the first time, that a combination of a DNA methylation and a histone deacetylase inhibitor, can reactivate the expression of more than a thousand genes in primary tumours of breast cancer patients.
Among these reactivated genes are those implicated in the regulation of cell proliferation, cell differentiation, programmed cell death, invasion, metastasis and immune recognition of tumour cells, such as p53, p21, eighteen members of the oxidative phosphorylation pathway, interferon-regulatory factors, NM23, negative regulators of Wnt signalling and Major Histocompatibility Complex Class-I and –II genes. In addition, these drugs down-regulate genes such as ABCB5, a recently identified member of the ABC transporter family implicated in multidrug resistance, which is predominantly expressed by tumour “stem” cells. Moreover, in this proof-of-principle study, the Mexican researchers demonstrate that this combination of epigenetic drugs can be safely administered concurrently with classical cytotoxic agents such as doxorubicin and cyclophosphamide, a common drug combination employed in the primary treatment of breast cancer.
Although this study is suggestive of increased anti-tumour effects no definitive conclusions can be drawn from it regarding the clinical efficacy of this therapy, because the study is single arm and the number of patients small; however, it is clearly suggestive that the epigenetic “principle” works and calls for increased preclinical and clinical efforts toward epigenetic cancer therapy.
Researchers used “epigenetic” drugs routinely employed for non-malignant conditions
One important aspect of this study, considers Dr Dueñas-Gonzalez, is that the “epigenetic” drugs used, are “very-well known” and have been routinely employed for almost 30 years to treat non-malignant conditions: the antihypertensive hydralazine and the antiepileptic valproic acid. Advocacy groups are claiming that “big pharma” companies are not interested in pursuing the preclinical and clinical development of this type of drugs –regardless of their potential antitumour efficacy– simply because they cannot be protected by patents and in consequence huge revenues cannot be expected. If the antitumour efficacy of these epigenetic drugs is eventually demonstrated, they would not only be added to the current anticancer armamentarium, but they will surely be affordable to the vast majority of cancer patients living in low and middle income countries, who find the newer anticancer agents prohibitively expensive. Dr Dueñas-Gonzalez’s group has recently completed a couple of single arm studies of this therapy with similar results and launched three placebo-controlled randomised trials in breast, ovarian and cervical cancer patients.
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research