Authors: Wing Han Wu, Future Science Group
A study published recently in Molecular and Cellular Biology has demonstrated that manipulating autophagy could potentially prove to be an effective strategy in the treatment of hematological cancers. Researchers from the Virginia Commonwealth University Massey Cancer Center (VA, USA) were able to induce autophagy through the use of the antitumor agent obatoclax and the simultaneous prevention of p62 production using a cyclin-dependent kinase inhibitor.
These results were obtained from both animal models and cultured multiple myeloma cells, and demonstrated that autophagy induced by the researchers using this combination of agents killed more cancer cells than just the anticancer agents alone.
“Therapies that are designed to block the early stages of autophagy do not offer the possibility of exploiting its potentially lethal effects,” commented Steven Grant, Shirley Carter Olsson and Sture Gordon Olsson Chair in Cancer Research at Massey Cancer Center. “Our strategy turns autophagy from a protective process into a toxic one, and these results suggest it could increase the effectiveness of a variety of cancer therapies that induce autophagy.”
By blocking p62, the researchers allowed Bik levels to accumulate in the cancer cells, which eventually triggered the process of apoptosis. Without the use of p62 cancer cells were not able to remove Bik, which is normally removed through the use of autophagosomes.
The research forms part of more than a decade of work from Steven Grant’s lab, whose research interests lie in the novel treatment and combination therapies in the treatment of multiple myelomas and other hematological cancers. The research has now been made available for licensing from the Virginia Commonwealth University office of research.
“We are now working to identify additional cyclin-dependent kinase inhibitors that can be used to disrupt autophagy,” commented Grant. “The ultimate goal will be to translate these findings into a clinical trial to test the therapy in patients with various blood cancers.”