News:
Tweets by @decarvalho_lab Our research was highlighted among the top 10 Notable advances of 2015 by Nature Medicine.
Immuno-oncology: Going viral
DNA methyltransferase inhibitors such as 5-azacitidine have shown efficacy in some hematological cancers, but it is still unclear how they slow tumor progression. New data from two groups point to the immune response as a key mediator of the beneficial effects of 5-azacitidine in a variety of tumor types (Cell 162, 961–973, 2015; Cell 162, 974–986, 2015). Scientists exposed human colorectal and ovarian cancer cell lines to 5-azacitidine, and they found that the drug activated an inflammatory response that is dependent on MDA5, a host defense protein responsible for detecting viral double-stranded RNA (dsRNA). The drug also boosted the expression of endogenous retroviruses.
Knockdown of MDA5 or of its downstream signaling components within either tumor cell lines or primary tumor samples abolished the ability of 5-azacitidine to suppress tumor cell growth and self-renewal in vitro. RNA-seq data from tumor samples from people with melanoma, who had been treated with a therapy known as anti-CTLA4 immune checkpoint blockade, revealed a strong correlation between the abundance of viral defense transcripts and the duration of clinical response, suggesting the relevance of patient response to immunotherapy.
Our 2015 Cell paper was recommended by Faculty of 1000 Post-publication peer review of the biomedical literature:
Below is the recomendation made by Professor Moriya Tsuji , from The Rockefeller University to F1000 Pharmacology & Drug Discovery section:
Our 2015 Cell paper was recommended by Faculty of 1000 Post-publication peer review of the biomedical literature:
Below is the recomendation made by Professor Emma Whitelaw , from La Trobe University (Australia) to F1000 Genomics & Genetics section:
Our research was named one of the top clinical cancer advances for 2012:
The American Society of Clinical Oncology (ASCO) annual report, now in its eighth year, is an independent review of clinical cancer research advances that have the greatest potential to improve patients' survival and quality of life. Compiled and edited under the guidance of 21 renowned experts in specific fields of cancer research, the report describes, in lay language, the most significant advances of the year, offering the public a window into the achievements, trends and challenges in oncology.
Our 2012 Cancer Cell paper was recommended by Faculty of 1000 Post-publication peer review of the biomedical literature:
Below is the recomendation made by Professor Frank Rosenbauer, from the Medical Faculty Münster to F1000 Genomics & Genetics section:
Cancer is characterized by global genome hypomethylation and regional hypermethylation of the CpG islands in the promoters of tumor suppressor genes. The authors hypothesized that the tumorigenic process might activate death-promoting genes which should be epigenetically silenced to prevent cancer cell elimination. The hypothesis was tested by the clustering of DNA methylation profiles from the colorectal cell line HCT116 and its daughter clones with a genetic disruption of major de novo and maintenance DNA methyltransferases (double knockout, DKO, cell lines). By further comparison of 566 CpG sites resistant to demethylation in DKO cells, with tumor and normal colon methylomes, a set of cancer-specific hypermethylated promoters was identified. Neither chromatin structure, nor gene architecture of these loci could explain their predisposition to DNA methylation, suggesting that these regions might become methylated to promote cancer cell survival. Gene expression analysis showed that the majority of hypermethylated promoters were associated with down-regulated genes in cancer cells. The same genes were found silent by methylation in lung adenocarcinoma, confirming their cancer-related nature. Interestingly, none of the candidate genes were reported as a classical tumor suppressor before. The authors provided a mechanistic explanation for one of them, IRAK3, an indirect inhibitor of anti-apoptotic SURVIVIN gene.
The discovered genes represent potentially good targets for future therapies because of the cancer specificity and epigenetic regulation. Novel targeted treatments should be developed since cancer-specific promoter hypermethylation is resistant to conventional demethylating drugs (5-Aza-2’-deoxycytidine), as reported in the study".
Epigenetics: Dissecting driving DNA methylations
Darren J. Burgess, from Nature Reviews Cancer, has just published a Research Highlight about our 2012 Cancer Cell paper. He highlighted the potential of our method to pinpoint various putative driver gene methylations on which cancer cells may particularly rely and in identify promising candidates for therapeutic re-activation in cancer treatment.
DNA Methylation Addiction Keeps Cancer Cells Alive
Epigenie, has just posted a Research Highlight about our Epigenetic Addiction concept.
Our PNAS paper was recommended by Faculty of 1000 Post-publication peer review of the biomedical literature:
Below is the recomendation made by Professor Stephan Beck, from University College London to F1000 Immunology section:
Surprising mechanism for the inheritance of DNA methylation patterns found
Our PLoS Genetics paper describing the DNMT3a/3b self-regulatory inheritance mechanism was highlighted by Epigenomics, where the critical role of this mechanism in preserving gene-expression patterns and cellular identity was highlighted.
HOT PAPERS IN BIOLOGY & BIOCHEMISTRY
ISI Web of knowledge, has just released its Essential Science Indicators and named our 2010 Nature Biotechnology review as a hot paper in Biology and Biochemistry.
5-mC Stabilizes High-Maintenance Methyltransferases
Epigenie, has just posted a Research Highlight about our PLoS Genetics paper.
Cura para o câncer está dentro de nós (Portuguese)
The Brazilian popular science Magazine 'Revista Conhecer', has just published an article about the potential of our research in the battle against cancer.
Our research was featured at 'Correio Braziliense' (Portuguese)
The Brazilian major Newspaper 'Correio Brasiliense', has just published a full page article about our research.
Our research was featured at 'Estado de Minas' (Portuguese)
The Brazilian major Newspaper 'Estado de Minas', has just published a full page article about our research.