Extracellular vesicle-derived VDAC1 protein promotes paclitaxel resistance through autophagy and mitophagy in gastric cancer

Gastric cancer (GC) is ranked as as the third most prevalent malignant tumor worldwide [1, 2]. Chemotherapy is considered the primary therapeutic approach for metastatic and unresectable GC [3]. Paclitaxel (PTX) is an anti-microtubule agent, and single therapy with PTX or PTX-based chemotherapy combined with other chemotherapy has demonstrated promising efficacy in clinical treatment in patients with advanced GC [4]. However, PTX-based chemotherapy is limited by acquired chemoresistance[5]. Mounting evidence have indicated that drug resistance in cancer cells is a major contributing factor for the failure of tumor treatment,resulting in the rapid recurrence, progression, and ultimately, patient mortality [6]. GC exhibits higher tissue heterogeneity and invasive behavior compared to other primary tumors [7]. Therefore, it is essential to promptly uncover the mechanisms underlying drug resistance in GC and meet unmet needs in GC treatment.