**5. Conclusions**

In the search for novel therapeutic options in cancer treatment, it has become increasingly clear that in addition to targeting specific proteins, the cellular membrane constitutes an attractive target. In accordance with our findings, we conclude that the endocannabinoid-like substance HU-585, used for MLT, can halt the growth and dissemination of neuroblastoma cancer cells through apoptosis and senescence induction. Although senescence is beneficial for arresting apoptosis-resistant cancer cells, inducing senescence in other situations promotes cancer relapse and secondary tumors. Based on our present findings of enhanced anti-tumorigenic effects of combination therapy by HU-585 with senolytic drugs, we propose that this approach might provide a novel complementary and less toxic therapeutic strategy for the treatment of refractory neuroblastomas. Further studies are needed to validate the efficacy of this novel approach and to explore its advantage over current established treatments.

**Author Contributions:** Conceptualization, R.M., A.T., H.G. and T.F.; methodology, T.F. and H.G.; software, D.D.B.-L., T.F. and H.G.; validation, T.F. and H.G.; formal analysis, E.C.-Z., S.W., S.P.-C., T.F. and H.G.; investigation, E.C.-Z., S.W., S.P.-C., T.F. and H.G.; resources, R.M., R.S., C.G.H. and D.D.B.-L.; data curation, E.C.-Z., S.W., S.P.-C., T.F. and H.G.; writing—original draft preparation, T.F. and H.G.; writing review and editing, R.S.; A.T. and R.M.; visualization, I.G.; supervision, T.F. and H.G. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Sheba Medical Center (IRB No. ANIM/803/12, since 10 February 2012).

**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.

**Data Availability Statement:** Data is contained within the article.

**Conflicts of Interest:** The authors declare no conflict of interest.
