Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment

Citation: Cell Death and Disease (2013) 4, e838; doi:10.1038/cddis.2013.350
Published online 10 October 2013


The induction of autophagy in response to metabolic and therapeutic stresses can have a prodeath or a prosurvival role, which contributes to the anticancer efficacy of these drugs as well as drug resistance.
Anticancer drugs induce different effects of autophagy on cell survival in different cancer types.
Autophagy as a prosurvival and resistance mechanism against chemotherapy treatment.
Autophagy-mediated cell death mechanism contributes to efficacy of anticancer drugs.
Targeting autophagy will hopefully provide a promising therapeutic strategy to circumvent resistance and enhance the effects of anticancer therapies for cancer patients.


http://www.nature.com/cddis/journal/v4/ ... 3350a.html

Resistance to receptor tyrosine kinase inhibitors in solid tumors: can we improve the cancer fighting strategy by blocking Autophagy?


Conclusions
The idea that targeting RTKs might be adopted as a suitable strategy for the clinical management of cancer has persisted since the moment it became clear that dysregulated RTK function is a frequent event in tumor cells [65]. Currently, the efficacy and tolerability of most of the available RTK inhibitors are not sufficient, and therefore, their continuous improvement is urgently needed. The chief problem with the use of RTK inhibitors in clinical oncology is their targeting of multiple RTKs, which can evoke several side effects [66]. On the other hand, a large issue that compromises the wider use in oncology is the development of drug resistance in treated patients [67]. Lately, there have been numerous reports on the cyto-protective role of autophagy related to the efficacy of RTK inhibitors [41, 42]. A relatively high incidence of autophagy during treatment with these inhibitors suggests that autophagy is a probable cause of primary or acquired drug resistance. It also justifies the numerous ongoing preclinical and clinical studies that are considering autophagy inhibitors to improve anti-cancer therapy [68]. The autophagy inhibitors CQ and bafilomycin A1 are frequently mentioned in combination therapy with RTK inhibitors [45–48, 52, 58]. In in vitro and in vivo studies, abolishing autophagosome formation had additive or synergistic effects regarding the anti-tumor activity of RTK inhibitors [60, 69].


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970224/