Evidence for cytoprotective autophagy in response to HER2-targeted monoclonal antibodies.
| Autor: | Elshazly AM; Pharmacology and Toxicology, Virginia Commonwealth University, United States., Elzahed AA; Pharmacology and Toxicology, Faculty of Pharmacy, Kafrelsheikh University, Egypt., Gewirtz DA; Dept. of Medicine, Virginia Commonwealth University, United States david.gewirtz@vcuhealth.org. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2024 Mar 07. Date of Electronic Publication: 2024 Mar 07. |
| DOI: | 10.1124/jpet.123.002048 |
| Abstrakt: | The advent of HER2-targeted monoclonal antibodies such as trastuzumab has significantly improved the clinical outcomes for patients with breast cancer overexpressing HER2, and more recently also for gastric cancers. However, the development of resistance, as is frequently the case for other antineoplastic modalities, constrains clinical efficacy. Multiple molecular mechanisms and signaling pathways have been investigated for their potential involvement in the development of resistance to HER2-targeted therapies, among which is autophagy. Autophagy is an inherent cellular mechanism whereby cytoplasmic components are selectively degraded to maintain cellular homeostasis via the generation of energy and metabolic intermediates. Although the cytoprotective form of autophagy is thought to predominate, other forms of autophagy have also been identified in response to chemotherapeutic agents in various tumor models; these include cytotoxic, cytostatic, and non-protective functional forms of autophagy. In this review, we provide an overview of the autophagic machinery induced in response to HER2-targeted monoclonal antibodies, with a focus on trastuzumab and trastuzumab-emtansine, in an effort to determine whether autophagy targeting or modulation could be translated clinically to increase their effectiveness and/or overcome resistance development. Significance Statement This manuscript is one in a series of papers that investigate the different roles of the autophagic machinery induced in response to versatile anti-neoplastic agents in various cancer models. This series designed in an attempt to build a conclusion whether autophagy targeting or modulation is an effective adjuvant strategy to increase the efficacy of chemotherapeutic agents. In this review, we shed the light on the relationship between the autophagic machinery and HER2 targeted therapies. (Copyright © 2024 American Society for Pharmacology and Experimental Therapeutics.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|