Research conducted by the Vall d’Hebron Insitute of Oncology (Barcelona, Spain) has validated Myc inhibition as a potential therapeutic strategy in glioma. Published recently in Nature Communications, the study targeted the Myc protein, which has a key role in the development of several types of cancer. The research, led by Laura Soucek is said to deliver the most conclusive preclinical results to date validating Myc as a therapeutic target in glioma.
Being implicated in gene transcription regulation, cellular proliferation, differentiation and apoptosis, the dysregulation of Myc is known to contribute to the development of many tumors, including cancer of the cervix, breast, colon, lung, pancreas and stomach.
In a study published last year, Soucek’s group succeeded in eradicating lung tumors in transgenic mice expressing Omomyc, a Myc inhibitor designed by Soucek. The results were encouraging as the repeated long-term treatment did not lead to any side effects postadministration and there was no evidence of resistance to therapy, one of the most challenging aspects of cancer treatment.
After a number of studies with positive results, Soucek’s group went on to demonstrate the therapeutic potential in glioblastoma and applied the Omomyc therapy to both human glioblastoma cell lines as well as patient-derived tumor xenografts.
“Our results undoubtedly show that Myc inhibition is effective in mouse tumors and, more notably, in human glioma,” Soucek explained. “This is the very first time that the use of Omomyc in human tumor specimens has been validated. We have also confirmed that Myc inhibition is effective against the tumor once it has developed, acts against tumor initiating cells, and prevents them from dividing, proliferating and forming the tumor again.”
With a similar structure to Myc, Omomyc acts by blocking transcription of the genes that are controlled by the protein, subsequently disrupting tumor cells and resulting in the induction of mitotic aberration and the halt of normal cell division, promoting cell death. “Importantly, the cells we treated with Omomyc went crazy. They showed problems with cell proliferation, with aberrant mitosis and the formation of cells with many nuclei that then died through mitotic catastrophe, that is, due to the inability to divide properly,” Soucek continued. “If we do not allow Myc to function normally, tumor cells cannot divide efficiently,” she affirms.
This research represents a step forward in the development of new therapeutic approaches for glioma patients as well as revealing crucial new insights into the mechanisms of Myc in tumor development. Soucek and her team are currently focusing on translating their research to the clinic, with preliminary results showing promise.
Sources: Annibali D, Whitfield JR, Favuzzi E et al. Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis. Nat Commun doi: 10.1038/ncomms5632 (2014) [Epub ahead of print]; Vall d’Hebron Insitute of Oncology press release