A Key Pathway to Cancer Resilience: The Role of Autophagy in Glioblastomas.

Autor:	Jandrey EHF; Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, Brazil., Bezerra M; Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, Brazil., Inoue LT; Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, Brazil., Furnari FB; Ludwig Institute for Cancer Research, University of California San Diego (UCSD), San Diego, CA, United States., Camargo AA; Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, Brazil., Costa ÉT; Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2021 Jun 10; Vol. 11, pp. 652133. Date of Electronic Publication: 2021 Jun 10 (Print Publication: 2021).
DOI:	10.3389/fonc.2021.652133
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Jandrey, Bezerra, Inoue, Furnari, Camargo and Costa.)
Databáze:	MEDLINE
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