Cancer Stem Cells and Pediatric Solid Tumors

Abstract

Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC), has been identified in many different types of solid tumors. These TSC, which are typically more resistant to chemotherapy and radiation compared to other tumor cells, have properties similar to normal stem cells including multipotency and the ability to self-renew, proliferate, and maintain the neoplastic clone. Much of the research on TSC has focused on adult cancers. With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies. We discuss what is currently known about pediatric solid TSC with specific focus on TSC markers, tumor microenvironment, signaling pathways, therapeutic resistance and potential future therapies to target pediatric TSC.

Expression and Functional Role of ALDH1 in Cervical Carcinoma Cells

“…However, a number of markers have been proposed to identify and isolate cancer stem cells including CD133, CD44, CD24, CD90, CD34, CD117, CD20, and aldehyde dehydrogenase (ALDH1) (Saini and Shoemaker, 2010;Friedman and Gillespie, 2011). ALDH1, a cytosolic enzyme, is responsible for oxidation of retinaldehydes to retinoids (Vasiliou et al, 2000).…”

Rationale and Design of a Phase 1 Clinical Trial to Evaluate HSV G207 Alone or with a Single Radiation Dose in Children with Progressive or Recurrent Malignant Supratentorial Brain Tumors

“…Children may respond differently to the virus than adults, both in terms of the oncolytic effect, based on our preclinical data suggesting that pediatric tumors may be more sensitive than adult tumors, and the immune response generated against the virus and/or tumor. 36 Furthermore, responses to G207 in adults were not dose dependent, with re- ). If there are no unacceptable (dose-limiting) toxicities in the initial cohorts, the dose levels will be repeated in combination with a single 5 Gy dose of radiation.…”

“…Importantly, CD133+ glioma and medulloblastoma cancer stem cells-which play a significant role in tumor aggressiveness, chemotherapy resistance, radioresistance, recurrence, and metastasis-were highly sensitive to G207 and showed no inherent resistance to oncolytic HSV-1 compared with CD133-tumor cells. 32,33,36 Furthermore, three pediatric patient-derived xenograft models of molecular group 3 medulloblastoma, which is the most difficult to treat subgroup of medulloblastoma and portends a poor prognosis, were very sensitive to killing by G207 in vitro, and G207 significantly prolonged survival in athymic nude mice bearing intracranial tumors compared with saline. 33 The safety and efficacy established in the three phase 1 adult studies and the promising preclinical data in pediatric patient-derived xenograft models form the bases to extend HSV G207 alone or combined with a single dose of radiation to the pediatric population.…”

Promises and challenges of exhausting pediatric neural cancer stem cells

“…Aberrant activation of the Notch, Wnt/β-catenin, and SHH pathways have been reported in several pediatric neural tumors including neuroblastomas, ependymomas, medulloblastomas, and primitive neuroectodermal tumors (60). Inhibitors of these pathways are therefore attractive targets for these tumors.…”