Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting

Pediatric neuroblastomas(NBs)are heterogeneous,aggressive,therapy-resistant embryonal tumours that originate from cells of neural crest(NC)origin and in particular neuroblasts committed to the sympathoadrenal progenitor cell lineage.Therapeutic resistance,post-therapeutic relapse and subsequent metastatic NB progression are driven primarily by cancer stem cell(CSC)-like subpopulations,which through their self-renewing capacity,intermittent and slow cell cycles,drug-resistant and reversibly adaptive plastic phenotypes,represent the most important obstacle to improving therapeutic outcomes in unfavourable NBs.In this review,dedicated to NB CSCs and the prospects for their therapeutic eradication,we initiate with brief descriptions of the unique transient vertebrate embryonic NC structure and salient molecular protagonists involved NC induction,specification,epithelial to mesenchymal transition and migratory behaviour,in order to familiarise the reader with the embryonic cellular and molecular origins and background to NB.We follow this by introducing NB and the potential NC-derived stem/progenitor cell origins of NBs,before providing a comprehensive review of the salient molecules,signalling pathways,mechanisms,tumour microenvironmental and therapeutic conditions involved in promoting,selecting and maintaining NB CSC subpopulations,and that underpin their therapy-resistant,self-renewing metastatic behaviour.Finally,we review potential therapeutic strategies and future prospects for targeting and eradication of these bastions of NB therapeutic resistance,post-therapeutic relapse and metastatic progression.

The 150 most important questions in cancer research and clinical oncology series: questions 94-101

Since the beginning of 2017,Cancer Communications(former title:Chinese Journal of Cancer)has published a series of important questions regarding cancer research and clinical oncology,to provide an enhanced stimulus for can-cer research,and to accelerate collaborations between institutions and investigators.In this edition,the following 8 valuable questions are presented.Question 94.The origin of tumors:time for a new paradigm?Question 95.How can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma?Question 96.Can we improve the treatment outcomes of metastatic pancreatic ductal adenocarcinoma through precision medicine guided by a combination of the genetic and proteomic information of the tumor?Question 97.What are the parameters that determine a competent immune system that gives a complete response to cancers after immune induction?Question 98.Is high local concentration of metformin essential for its anti-cancer activity?Question 99.How can we monitor the emergence of cancer cells anywhere in the body through plasma testing?Question 100.Can phytochemicals be more specific and efficient at targeting P-glycoproteins to overcome multi-drug resistance in cancer cells?Question 101.Is cell migration a selectable trait in the natural evolution of carcinoma?