Autophagy and cancer drug resistance in dialogue: Pre-clinical and clinical evidence

• Published in: Cancer letters 2023-08, Vol.570, p.216307-216307, Article 216307
• Main Authors: Qin, Yi, Ashrafizadeh, Milad, Mongiardini, Vera, Grimaldi, Benedetto, Crea, Francesco, Rietdorf, Katja, Győrffy, Balázs, Klionsky, Daniel J., Ren, Jun, Zhang, Wei, Zhang, Xianbin
• Format: Article
• Language: English
• Subjects: Apoptosis; Autophagy; Cancer drug resistance; Cell death; Chemoresistance; Drug sensitivity
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2023.216307

The emergence of drug resistance is a major challenge for oncologists. Resistance can be categorized as acquired or intrinsic; the alteration of several biological mechanisms contributes to both intrinsic and acquired resistance. Macroautophagy/autophagy is the primary process in eukaryotes for the degradation of macromolecules and organelles. This process is critical in maintaining cellular homeostasis. Given its function as either a pro-survival or a pro-death phenomenon, autophagy has a complex physio-pathological role. In some circumstances, autophagy can confer chemoresistance and promote cell survival, whereas in others it can promote chemosensitivity and contribute to cell death. The role of autophagy in the modulation of cancer drug resistance reflects its impact on apoptosis and metastasis. The regulation of autophagy in cancer is mediated by various factors including AMP-activated protein kinase (AMPK), MAPK, phosphoinositide 3-kinase (PI3K)-AKT, BECN1 and ATG proteins. Non-coding RNAs are among the main regulators of autophagy, e.g., via the modulation of chemoresistance pathways. Due to the significant contribution of autophagy in cancer drug resistance, small molecule modulators and natural compounds targeting autophagy have been introduced to alter the response of cancer cells to chemotherapy. Furthermore, nanotherapeutic approaches based on autophagy regulation have been introduced in pre-clinical cancer therapy. In this review we consider the potential for using autophagy regulators for the clinical treatment of malignancies. [Display omitted] •Cancer drug resistance is a main cause of therapeutic failure in cancer patients.•Autophagy can enhance drug resistance by inhibiting apoptosis and promoting metastasis.•Autophagy modulators can counteract cancer drug resistance.•Nanostructure-mediated autophagy regulation affects drug resistance.•Non-coding RNA-mediated autophagy can alleviate drug resistance.