Teixeira Ana Beatriz da Silva, Ramalho Maria Carolina Clares, Souza Izadora de, Andrade Izabela Amélia Marques de, Osawa Isabeli Yumi Araújo, Guedes Camila Banca, Oliveira Beatriz Silva de, Souza Filho Cláudio Henrique Dahne de, Silva Tainá Lins da, Moreno Natália Cestari, Latancia Marcela Teatin, Rocha Clarissa Ribeiro Reily
Universidade Federal de São Paulo (UNIFESP), Departamento de Oncologia Clínica e Experimental, São Paulo, SP, Brazil.
National Institutes of Health, National Institute of Child Health and Human Development, Laboratory of Genomic Integrity, Bethesda, MD, USA.
Genet Mol Biol. 2024 May 31;47(Suppl 1):e20230317. doi: 10.1590/1678-4685-GMB-2023-0317. eCollection 2024.
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.
在寻找克服癌症治疗中耐药性发展所带来挑战的替代方法时，自噬调节已成为一种有前景的替代方法，并且在临床试验中取得了良好效果。然而，这些研究大多忽略了一种新型的选择性自噬：伴侣介导的自噬（CMA）。自其被发现以来，对CMA在肿瘤进展中作用的研究迅速加速。因此，我们现在明白应激条件是调节癌细胞中CMA的主要信号。反过来，CMA介导的蛋白质降解可为肿瘤发生提供重要优势，因为肿瘤抑制蛋白是CMA的作用靶点。肿瘤微环境与CMA之间的这种相互作用在建立治疗抗性方面也起着关键作用，使得这一讨论成为本综述的重点。因此，我们强调抑制溶酶体相关膜蛋白2A（LAMP2A）如何能够增强癌细胞对多种药物的敏感性，正如在某些情况下CMA活性的下调会导致耐药性一样。鉴于此情况，识别CMA的选择性调节剂以增强治疗反应非常重要。
