Spatiotemporal switching signals for cancer stem cell activation in pediatric origins of adulthood cancer:Towards a watch-and-wait lifetime strategy for cancer treatment

Pediatric origin of cancer stem cell hypothesis holds great promise and potential in adult cancer treatment, however; the road to innovation is full of obstacles as there are plenty of questions left unanswered. First, the key question is to characterize the nature of such stem cells (concept). Second, the quantitative imaging of pediatric stem cells should be implemented(technology). Conceptually, pediatric stem cell origins of adult cancer are based on the notion that plasticity in early life developmental programming evolves local environments to cancer. Technologically, such imaging in children is lacking as all imaging is designed for adult patients. We postulate that the need for quantitative imaging to measure space-time changes of plasticity in early life developmental programming in children may trigger research and development of the imaging technology. Such quantitative imaging of pediatric origin of adulthood cancer will help develop a spatiotemporal monitoring system to determine cancer initiation and progression. Clinical validation of such speculative hypothesis-that cancer originates in a pediatric environment-will help implement a wait-andwatch strategy for cancer treatment.

Hunting down the dominating subclone of cancer stem cells as a potential new therapeutic target in multiple myeloma: An artificial intelligence perspective

The development of single-cell subclones,which can rapidly switch from dormant to dominant subclones,occur in the natural pathophysiology of multiple myeloma(MM)but is often"pressed"by the standard treatment of MM.These emerging subclones present a challenge,providing reservoirs for chemoresistant mutations.Technological advancement is required to track MM subclonal changes,as understanding MM's mechanism of evolution at the cellular level can prompt the development of new targeted ways of treating this disease.Current methods to study the evolution of subclones in MM rely on technologies capable of phenotypically and genotypically characterizing plasma cells,which include immunohistochemistry,flow cytometry,or cytogenetics.Still,all of these technologies may be limited by the sensitivity for picking up rare events.In contrast,more incisive methods such as RNA sequencing,comparative genomic hybridization,or whole-genome sequencing are not yet commonly used in clinical practice.Here we introduce the epidemiological diagnosis and prognosis of MM and review current methods for evaluating MM subclone evolution,such as minimal residual disease/multiparametric flow cytometry/next-generation sequencing,and their respective advantages and disadvantages.In addition,we propose our new single-cell method of evaluation to understand MM's mechanism of evolution at the molecular and cellular level and to prompt the development of new targeted ways of treating this disease,which has a broad prospect.

Convergence of normal stem cell and cancer stem cell developmental stage:Implication for differential therapies

Increased evidence shows that normal stem cells may contribute to cancer development and progression by acting as cancer-initiating cells through their interactions with abnormal environmental elements.We postulate that normal stem cells and cancer stem cells (CSC) possess similar mechanisms of self-renewal and differentiation.CSC can be the key to the elaboration of anti-cancer-based therapy.In this article,we focus on a controversial new theme relating to CSC.Tumorigenesis may have a critical stage characterized as a "therapeutic window",which can be identified by asso-ciation of molecular,biochemical and biological events.Identifying such a stage can allow the production of more effective therapies (e.g.manipulated stem cells) to treat several cancers.More importantly,confirming the existence of a similar therapeutic window during the conversion of normal stem cells to malignant CSC may lead to targeted therapy specifically against CSC.This conversion information may be derived from investigating the biological behaviour of both normal stem cells and cancerous stem cells.Currently,there is little knowledge about the cellular and molecular mechanisms that govern the initiation and maintenance of CSC.Studies on co-evolution and interdependence of cancer with normal tissues may lead to a useful treatment paradigm of cancer.The crosstalk between normal stem cells and cancer formation may converge developmental stages of different types of stem cells (e.g.normal stem cells,CSC and embryonic stem cells).The differential studies of the convergence may result in novel therapies for treating cancers.

Application of artificial intelligence in pediatrics: past, present and future

Artificial intelligence (AI) is a very active computer science research field aiming to develop systems that mimic human intelligence and is helpful in many human activities,including medicine.Therefore,it is no surprise that innovation plays an important role in delivering better medical and health.