| Autor: |
Teixeira ABDS; Universidade Federal de São Paulo (UNIFESP), Departamento de Oncologia Clínica e Experimental, São Paulo, SP, Brazil., Ramalho MCC; Universidade Federal de São Paulo (UNIFESP), Departamento de Oncologia Clínica e Experimental, São Paulo, SP, Brazil., Souza I; Universidade Federal de São Paulo (UNIFESP), Departamento de Oncologia Clínica e Experimental, São Paulo, SP, Brazil., Andrade IAM; Universidade Federal de São Paulo (UNIFESP), Departamento de Oncologia Clínica e Experimental, São Paulo, SP, Brazil., Osawa IYA; Universidade Federal de São Paulo (UNIFESP), Departamento de Oncologia Clínica e Experimental, São Paulo, SP, Brazil., Guedes CB; Universidade Federal de São Paulo (UNIFESP), Departamento de Oncologia Clínica e Experimental, São Paulo, SP, Brazil., Oliveira BS; Universidade Federal de São Paulo (UNIFESP), Departamento de Oncologia Clínica e Experimental, São Paulo, SP, Brazil., Souza Filho CHD; Universidade Federal de São Paulo (UNIFESP), Departamento de Oncologia Clínica e Experimental, São Paulo, SP, Brazil., Silva TLD; Universidade Federal de São Paulo (UNIFESP), Departamento de Oncologia Clínica e Experimental, São Paulo, SP, Brazil., Moreno NC; National Institutes of Health, National Institute of Child Health and Human Development, Laboratory of Genomic Integrity, Bethesda, MD, USA., Latancia MT; National Institutes of Health, National Institute of Child Health and Human Development, Laboratory of Genomic Integrity, Bethesda, MD, USA., Rocha CRR; Universidade Federal de São Paulo (UNIFESP), Departamento de Oncologia Clínica e Experimental, São Paulo, SP, Brazil. |
| Abstrakt: |
In the search for alternatives to overcome the challenge imposed by drug resistance development in cancer treatment, the modulation of autophagy has emerged as a promising alternative that has achieved good results in clinical trials. Nevertheless, most of these studies have overlooked a novel and selective type of autophagy: chaperone-mediated autophagy (CMA). Following its discovery, research into CMA's contribution to tumor progression has accelerated rapidly. Therefore, we now understand that stress conditions are the primary signal responsible for modulating CMA in cancer cells. In turn, the degradation of proteins by CMA can offer important advantages for tumorigenesis, since tumor suppressor proteins are CMA targets. Such mutual interaction between the tumor microenvironment and CMA also plays a crucial part in establishing therapy resistance, making this discussion the focus of the present review. Thus, we highlight how suppression of LAMP2A can enhance the sensitivity of cancer cells to several drugs, just as downregulation of CMA activity can lead to resistance in certain cases. Given this panorama, it is important to identify selective modulators of CMA to enhance the therapeutic response. |
