conditions, including cancer 1. Therefore, targeting autophagy is of interest for the treatment of cancer, which was the focus of this research topic (Figure 1).The importance of autophagy in cancer was highlighted in the review of Kurganovs et al. that focused on the role of autophagy during the development of prostate cancer, and described how autophagy impacts on the therapeutic response. Autophagy is also of importance in lung cancer Indeed, autophagy is widely considered as a pro-survival mechanism, especially for cells under stress, among which cancer cells. This argues for the inhibition of autophagy as a promising strategy for cancer therapy. In this respect, Koll et al. demonstrated that the glycan-binding protein Galectin-9 was cytotoxic for malignant B cells by inhibiting the proper execution of autophagy. Here, malignant B cell lines with lower LC3B-I expression levels were more sensitive towards Galectin-9 treatment. This data suggests that Galectin-9 sensitivity is related to basal levels of autophagy flux, whereby cells that rely more on autophagy for their survival are more sensitive to the inhibition of this pathway. However, autophagy can also be a cell death pathway Together, autophagy is a multifaceted pathway and promising target for cancer therapy. Although not part of this research topic, autophagy-modulation may also be used to steer anti-cancer immune responses, as also highlighted in a recent research topic of Frontiers 2. Interestingly, both the modulation at the cancer side, as well as the regulation at the immune effector cell side can improve anti-cancer immune responses. Recently, this has also been demonstrated for chimeric antigen receptor (CAR) T cell therapy, a relatively novel immunotherapeutic strategy that revolutionized the landscape of cancer immunotherapy. Specifically, activation of autophagy in the CAR T cells improved their persistence and anti-tumor activity 3, whereas inhibition of autophagy in the cancer cells made them more vulnerable to CAR T cell-induced cytotoxicity 4, 5.However, an issue that still needs to be addressed to enable full clinical translation is the current lack of autophagy modulators and especially inhibitors that are suitable for clinical use.Chloroquine and its derivative hydroxychloroquine are clinically approved autophagy drugs with reasonable safety profiles, but their clinical efficacy in cancer therapy remains limited 6.Numerous novel autophagy inhibitors have been developed over the past decade, but their systemic use is commonly hampered by unwanted side-effects. Hence, strategies for cancerspecific targeted delivery of autophagy inhibitors are of interest to be further developed 7. In addition, characterizing autophagy-modulating capacities of already clinically approved drugs may be useful to accelerate the implementation of autophagy targeting into clinical practice 8.Thus, as highlighted by this research topic, autophagy is a versatile pathway that is a promising target for cancer therapy (Figure 1). Future research should however be focused on the development of more specific modulators and/ or modalities for targeted delivery, to advance autophagy modulation as a therapeutic strategy in cancer therapy.
Valerie R. Wiersma (Mon,) studied this question.