Search valid Myc inhibition as effective therapeutic strategy for glioma -
Research by the Vall d'Hebron Institute of Oncology (VHIO) evidence Preclinical results the day to more conclusive validation of myc inhibition as a therapeutic strategy in gliomas - a type of aggressive tumor that outsmarts current anticancer therapies known. The study by Laura Soucek, principal investigator of VHIO's Mouse Models of Cancer Therapies Group, published today in Nature Communications not only represents an important step in providing ultimately brain glioma patients with new therapeutic avenues, but also reveals new insights into the biology of Myc that could favor the impact on its therapeutic potential.
in a study published last year, the group succeded in eradicating lung tumors in transgenic mice by adopting the same strategy involving expression Omomyc, Myc inhibitor designed by Soucek. They also confirmed that there were no side effects after administration of repeated treatment and long term. Above all, there was no evidence of resistance to therapy - one of the greatest challenges in the treatment of cancer. These results confirm Myc inhibition as a sound and effective therapeutic strategy for the development of new drugs against cancer.
Soucek and his group were to raise the bar even higher. First, focus on based on gene expression in the experimental study therapy progressed and re-programmed on the development of a drug based Omomyc manageable. Second, the group continued to show the effectiveness of Myc inhibition in different tumors and, above and beyond the transgenic models, they showed the same success in human tumors using a technique that transfers cells human cancer in immunodeficient mice. " When presenting the initial results at the preclinical level, our main concern was how to not show these results in human tumors " said Laura Soucek . " First, we focused on how they might apply to other tissues and other types of more aggressive tumors for which there is no treatment effective, so that Omomyc solution could make all the difference. We also sought to reveal new knowledge Omomyc on the mechanism of action in cancer cells. " It appears that Soucek group has now found answers to all these questions. " All our efforts must now focus on finding a way for the pharmacological administration. Based on our ongoing research, we have every reason to be optimistic " says Soucek.
A new therapy for tumor most common and aggressive brain
After four years' extensive research, these results bring more good news and with them, preclinical inhibition Myc was also validated as a therapeutic strategy against astrocytoma, a type of glioma in vivo in mouse models in vitro stem cells in these tumors. In these models, which develop advanced brain tumors with clear neurological symptoms, treatment with Omomyc transgene drastically reduces tumors and improves symptoms until the mouse recovers and starts acting quite normally. Mice treated with Omomyc survived, while those without, do not. " We do not prevent there " says Soucek " we applied therapy with the two Omomyc lines of human glioblastoma cells and mice with tumor xenografts derived from patients that faithfully recapitulate human tumors. " the therapeutic effect of Omomyc is its structure, which is similar to that Myc, to block the transcription of genes controlled by this protein. Myc inhibition leads to "defects" in the tumor cells and often results in death inducing mitotic aberrations, normal cell division and stop.
" Our results show undoubtedly that Myc inhibition is effective in mouse tumors and more particularly in human glioma. " she explains. The group demonstrated the therapeutic potential of additional Omomyc through their clinical approach against the most common and aggressive primary tumor to affect the adult central nervous system - glioblastoma, for which there is a critical call to improve treatment current that are largely ineffective. " This is the first time that the use of Omomyc in human tumor samples have been validated. We also confirmed that the Myc inhibition is effective against the tumor once it developed acts against tumor initiating cells, and prevents them from dividing, proliferate and form again the tumor. "continues Dr. Soucek.
mitotic catastrophe that the therapeutic mechanism of inhibition of myc
The Myc protein plays an important role in regulating gene transcription, regulating the expression of up to 15% of human genes. It is also involved in cell proliferation, differentiation and apoptosis (programmed cell death is necessary for tissue regeneration and the removal of damaged cells). However, alterations in this protein cause uncontrolled cell proliferation, which may lead to developing cancer in different tissues. myc deregulation is in fact present in most tumors, such as cervical cancer, breast, colon, lung, pancreas and stomach.
Brain tumors can now be added to this list of potential tumors can be targeted with Myc inhibition.
At the cellular level, we now know more about its mechanism of action. Whatever the experimental system used, the Myc inhibition reduces proliferation and increasing cell death. " Importantly, the cells we dealt with Omomyc went crazy. They showed problems with cell proliferation, aberrant mitosis and cell formation with many nuclei that died by mitotic catastrophe, which is due to the inability to properly divide " says Laura Soucek. " If we do not allow Myc function normally, tumor cells can not divide efficiently. " she says. Myc is deregulated in healthy cells, therefore, its inhibition does not cause significant side effects that may limit the use of this therapy.
Finally, the Myc inhibition as a therapeutic strategy against tumors of the brain opens up new avenues tagging new hope and improvement of more effective therapies for patients. Soucek and his team are focused on translating their findings into the clinic. Preliminary results show promise.
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