Autophagy is not uniformly cytoprotective: a personalized medicine approach for autophagy inhibition as a therapeutic strategy in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related death worldwide. In addition to surgical resection, which is considered first-line treatment at early stages of the disease, chemotherapy and radiation are widely used when the disease is advanced. Of multiple responses that may occur in the tumor c...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Biochimica et biophysica acta Jg. 1860; H. 10; S. 2130 - 2136
Hauptverfasser: Saleh, Tareq, Cuttino, Laurie, Gewirtz, David A.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Netherlands Elsevier B.V 01.10.2016
Schlagworte:
Antineoplastic Agents - therapeutic use
Apoptosis
Apoptosis - drug effects
Apoptosis - radiation effects
Autophagy
Autophagy - drug effects
Autophagy - radiation effects
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Carcinoma, Non-Small-Cell Lung - radiotherapy
Cell Proliferation - drug effects
Cell Proliferation - radiation effects
Cell Survival - drug effects
Cell Survival - radiation effects
cell viability
Chemotherapy
cytotoxicity
death
drug therapy
drugs
Gene Expression Regulation, Neoplastic - drug effects
Gene Expression Regulation, Neoplastic - radiation effects
Humans
lung neoplasms
medicine
neoplasm cells
Non-cytoprotective
Non-Small cell lung cancer
patients
Precision Medicine
Radiation
resection
Sensitization
Chemotherapy
Radiation
Sensitization
Autophagy
Non-cytoprotective
Non-Small cell lung cancer
Apoptosis
ISSN:0304-4165, 0006-3002, 1872-8006
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Lung cancer is the leading cause of cancer-related death worldwide. In addition to surgical resection, which is considered first-line treatment at early stages of the disease, chemotherapy and radiation are widely used when the disease is advanced. Of multiple responses that may occur in the tumor cells in response to cancer therapy, the functional importance of autophagy remains equivocal; this is likely to restrict current efforts to sensitize this malignancy to chemotherapy and/or radiation by pharmacological interference with the autophagic response. In this review, we attempt to summarize the current state of knowledge based on studies that evaluated the function of autophagy in non-small cell lung cancer (NSCLC) cells in response to radiation and the most commonly used chemotherapeutic agents. In addition to the expected prosurvival function of autophagy, where autophagy inhibition enhances the response to therapy, autophagy appears also to have a “non-cytoprotective” function, where autophagy blockade does not affect cell viability, clonogenicity or tumor volume in response to therapy. In other cases, autophagy may actually mediate drug action via expression of its cytotoxic function. These observations emphasize the complexity of autophagy function when examined in different tumor cell lines and in response to different chemotherapeutic agents. A more in-depth understanding of the conditions that promote the unique functions of autophagy is required in order to translate preclinical findings of autophagy inhibition to the clinic for the purpose of improving patient response to chemotherapy and radiation. •Autophagy induced by chemotherapy or radiation in non-small cell lung cancer can be protective, cytotoxic or nonprotective.•It is premature to expect that autophagy inhibition will lead to sensitization to any particular form of therapy.•The outcome of current clinical trials may erroneously indicate that this therapeutic strategy is untenable.•Biomarkers of cytoprotective autophagy must be identified in order for autophagy to become a viable clinical strategy.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
ObjectType-Review-2
ObjectType-Feature-2
ISSN:0304-4165
0006-3002
1872-8006
DOI:10.1016/j.bbagen.2016.06.012