Therapeutic Window, a Critical Developmental Stage for Stem Cell Therapies
Shengwen Calvin Li,
Brent A. Dethlefs,
William G. Loudon.
In children, cancers are the deadliest of diseases and second only to accidents as the leading cause of death. The deadliest of the brain cancers are the malignant gliomas. Approximately two-thirds of children can survive less malignant types of brain cancers, however, in ~67% of these survivors recurs under the current regimes of surgery followed by administration of high doses toxic drugs and exposure to high doses of radiation. Even more distressing is that fortunate survivors are generally left with life-long cognitive disabilities. A new medical approach is desperately needed. Stem cells, with their natural ability to seek out brain tumors, could be used to accurately deliver therapy directly to the cancer sparing normal tissues for suppression of tumor growth. Despite exciting initial reports, clinical potency of stem cell therapy in animal brain tumor models has to date proven disappointing. Attempts to extrapolate the animal study results to humans are stymied by the fact that stem cells are heterogeneous, resulting in differences in their efficacy. Indeed, therapeutic success relies on an effective strategy to select for a stem cell sub-population within some particular stage of the development at which they are competitive and capable of targeting brain tumors. To improve this during developmental path, concept of a ‘ therapeutic window ’ is proposed. The “therapeutic window” for stem cells or more specifically a “biochemical therapeutic window” can be determined from biochemical assays and a “biological therapeutic window” from biological assays or even a molecular window from genetic description. Taken together, we can use selective processes to generate more effective stem cells to treat cancers as is clearly needed today.
Keywords: Pediatric brain tumor, stem cells, therapy, tumor-targeting, Developmental Stage, MALIGNANT BRAIN, CANCER-RELATED DEATH IN CHILDREN, CNS cancers, pediatric hematological malignancies, clinical research, glioblastoma multiforme, microsatellites, central nervous system, adjuvant therapies, chemotherapy, radiation therapy, surgical resection, istological, genetic spectra, clinical prognoses, long-term responses, PRIMARY TREATMENT MODALITIES, neurosurgeons, oncologically, postradiation, chemotherapeutic regimens, pediatric medulloblastoma, pharmacokinetically, antitumor efficacy, osmotic breaching of the blood-brain barrier (BBB), spatial and temporal distribution of molecular lipo, BBB permeabilization, cancer cells, cytotoxic therapies, novel targeted therapies, antiangiogenic antibody, tumor oxygenation, malignant astrocytoma, neurological toxicity, tumor-tracking, cancer satellite foci, neuroprotective properties, immune regulatory functions, transcriptome analyses, nerve injury, neurons, neuriteinducing factors, axon guidance, neural cell adhesion molecules, chemokines, secretion of matrix, metalloproteinases, therapeutic activation, chemokine receptors, heterogeneous, targeting brain tumors, HYPOTHESIS, therapeutic efficacy of stem cells, drug dosage, matrix remodeling, biological behavior, biological therapeutic window, enzymatic activities, in vivo, cell development, intervention, life cycle of cancer cells, embryonic organ transplantation, embryonic stem cells, human blastocysts, endoderm, mesoderm, optimal gestational, teratoma formation, embryonic pig organ, gestational stages, maximal liver growth, teratoma-free, insulin-secreting capacity, respiratory system, treatment of diabetes, pluripotent cells, phenotypic analysis, myocardial infarction, healing pathways, inflammation, biochemical mechanisms, laboratory assays, anti-tumor treatment, organotypic brain, intracranial brain tumor model, three dimensional (3D) system, zymography, 3D collagen, synthetic polymers, microfluidic chambers, autologous stem cell transplantation, lymphodepletion period, proliferation of polyclonal T cells, tissue biopsy, Imaging techniques, prognostic tools, Neuro-oncology
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