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By Christina Towers, PhD.
Autophagy is a cellular recycling process and most often a pro-survival mechanism that regulates cellular homeostasis. On the contrary, apoptosis is an extensively conserved and elaborate programmed cell death process, and it is well established that the two processes are often opposing forces within the cell. Despite the agreed upon notion that autophagy can protect cells from apoptosis, the mechanistic link has yet to be elucidated. This is especially important given the 60 (and growing) number of clinical trials that are currently underway inhibiting autophagy in cancer in combination with other chemotherapies and targeted therapeutics.
The field is hopeful that autophagy inhibition will enhance drug induced cell death. A recent publication by Fitzwalter et al. in the journal Developmental Cell identifies FOXO3a mediated regulation of PUMA as a critical link between autophagy and apoptosis1. Most importantly, they also show that cell death induced by clinically relevant targeted therapeutics can be greatly improved upon when combined with autophagy inhibitors; and this mechanism is dependent on FOXO3a mediated regulation of PUMA.
Find out more about the publication and its relevance to the field in this chat with the first author graduate student:
 Your browser does not support the audio element. | Brent E. Fitzwalter is a PhD candidate in the laboratory of Andrew Thorburn at the Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA |
Christina Towers, PhD
University of Colorado (AMC)
Dr. Towers studies the roles of autophagy, apoptosis and cell death in cancer.
References
- Autophagy Inhibition Mediates Apoptosis Sensitization in Cancer Therapy by Relieving FOXO3a Turnover. Fitzwalter BE, Towers CG, Sullivan KD, Andrysik Z, Hoh M, Ludwig M, O'Prey J, Ryan KM, Espinosa JM, Morgan MJ, Thorburn A.Dev Cell. 2018 Mar 12;44(5):555-565.e3. doi: 10.1016/j.devcel.2018.02.014.
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