| Full text | |
| Author(s): |
Jandrey, Elisa Helena Farias
[1]
;
Bezerra, Marcelle
[1]
;
Inoue, Lilian Tiemi
[1]
;
Furnari, Frank B.
[2]
;
Camargo, Anamaria Aranha
[1]
;
Costa, Erico Tosoni
[1]
Total Authors: 6
|
| Affiliation: | [1] Hosp Sirio Libanes, Mol Oncol Ctr, Sao Paulo - Brazil
[2] Univ Calif San Diego UCSD, Ludwig Inst Canc Res, San Diego, CA - USA
Total Affiliations: 2
|
| Document type: | Review article |
| Source: | FRONTIERS IN ONCOLOGY; v. 11, JUN 10 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
There are no effective strategies for the successful treatment of glioblastomas (GBM). Current therapeutic modalities effectively target bulk tumor cells but leave behind marginal GBM cells that escape from the surgical margins and radiotherapy field, exhibiting high migratory phenotype and resistance to all available anti-glioma therapies. Drug resistance is mostly driven by tumor cell plasticity: a concept associated with reactivating transcriptional programs in response to adverse and dynamic conditions from the tumor microenvironment. Autophagy, or ``self-eating{''}, pathway is an emerging target for cancer therapy and has been regarded as one of the key drivers of cell plasticity in response to energy demanding stress conditions. Many studies shed light on the importance of autophagy as an adaptive mechanism, protecting GBM cells from unfavorable conditions, while others recognize that autophagy can kill those cells by triggering a non-apoptotic cell death program, called `autophagy cell death' (ACD). In this review, we carefully analyzed literature data and conclude that there is no clear evidence indicating the presence of ACD under pathophysiological settings in GBM disease. It seems to be exclusively induced by excessive (supra-physiological) stress signals, mostly from in vitro cell culture studies. Instead, pre-clinical and clinical data indicate that autophagy is an emblematic example of the `dark-side' of a rescue pathway that contributes profoundly to a pro-tumoral adaptive response. From a standpoint of treating the real human disease, only combinatorial therapy targeting autophagy with cytotoxic drugs in the adjuvant setting for GBM patients, associated with the development of less toxic and more specific autophagy inhibitors, may inhibit adaptive response and enhance the sensibility of glioma cells to conventional therapies. (AU) | |
| FAPESP's process: | 16/07463-4 - MOLECULAR CHARACTERIZATION AND FUNCTIONAL STUDY OF ADAM23 GENE FOR PROGRESSION OF DIFFUSE GLIOMAS. |
| Grantee: | Erico Tosoni Costa |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 16/06857-9 - ADAM23 signaling in glioblastomas and its role in Wnt pathway control |
| Grantee: | Elisa Helena Farias Jandrey |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |