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Targeting Subgroup-specific Cancer Epitopes for Effective Treatment of Pediatric Medulloblastoma
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Sidharth Mahapatra, Naveenkumar Perumall
Although the mainstay of therapy for medulloblastoma remains unchanged, current focus has shifted to not only improving five-year event-free survival but also long-term treatment-related sequelae resulting from cytotoxic therapies instituted during critical periods of growth and development. With a more refined understanding of molecular pathways implicated in phenotypic transformation to medulloblastoma, multiple viable pre-clinical models have been generated for the SHH and WNT subgroups, thereby facilitating the development and testing of targeted anti-neoplastic therapies, some of which are now under clinical investigation.
Pediatric Oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Stephen Lowis, Rachel Cox, John Moppett, Helen Rees
Recent developments in the molecular biology of medulloblastoma have given profound insights into the causes, cell of origin, and importantly, the curability of this disease. The developments have been rapid and astonishing, coming from extensive international collaboration and multi-national clinical trials.
Embryonal Tumors
Published in David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack, Brain and Spinal Tumors of Childhood, 2020
Other imaging examinations need not be used at diagnosis in the usual clinical presentation of medulloblastoma. Indeed, bone or bone marrow metastases at diagnosis are rare, thus isotopic bone scanning and bone marrow examination are not routinely recommended.
Overview and recent advances in the targeting of medulloblastoma cancer stem cells
Published in Expert Review of Anticancer Therapy, 2021
The overall survival rates of children with medulloblastoma using current treatment regimens is among the highest of all pediatric central nervous system malignancies, with the majority of children surviving their disease. This success comes at a steep cost, however, with many children having life-long systemic side effects. Furthermore, children with refractory disease or who develop disease recurrence have very poor prognosis, and new treatment strategies are urgently needed. Our understanding of medulloblastoma pathogenesis has continued to increase; however, with significant insights into the drivers of medulloblastoma development and of the molecular heterogeneity which separates different subgroups. Less is known about the intratumoral heterogeneity and hierarchy and how CSCs can recapitulate tumors after the completion of standard of care therapy.
Clinical and pre-clinical utility of genomics in medulloblastoma
Published in Expert Review of Neurotherapeutics, 2018
Advances in biology have significantly changed our clinical and preclinical approach to medulloblastoma. Current approaches are significantly limited and have resulted in stagnant outcomes over the past 30 years, warranting new and novel approaches. Integrated genomic studies over the past decade have shown that despite morphological homogeneity there is dramatic intertumoral heterogeneity suggesting that medulloblastoma actually comprises multiple different diseases. As such, medulloblastoma can no longer be considered a single entity and effective clinical care; risk stratification and drug development requires the division of medulloblastoma into at least four distinct subgroups. Risk stratification in particular has benefited from incorporating molecularly informed approaches where low risk-risk patients can benefit from therapy de-escalation and a resulting reduction in long-term cognitive side effects. At the same time, it is clear that very-high risk patients are not benefitting from current treatments, and new upfront approaches are urgently required. Applying cross-species genomics to generate preclinical models, which faithfully recapitulate the human condition, hold tremendous promise in vetting new compounds in combinatorial therapy to guide the next generation of clinical trials. Nevertheless, our understanding of medulloblastoma has greatly increased over the past decade and molecularly driven preclinical studies are ongoing to help inform the next generation of clinical trials.
Hypothyroidism after craniospinal irradiation with proton or photon therapy in patients with medulloblastoma
Published in Pediatric Hematology and Oncology, 2018
Kevin Bielamowicz, M. Fatih Okcu, Rona Sonabend, Arnold C. Paulino, Susan G. Hilsenbeck, Zoann Dreyer, Hilary Suzawa, Rosalind Bryant, Adekunle Adesina, Robert Dauser, Anita Mahajan, Murali Chintagumpala
Medulloblastoma is the most common malignant brain tumor in children.1 Multimodality treatment with surgical resection, CSI, and multiagent chemotherapy has improved survival in children with medulloblastoma greater than three years of age at diagnosis. Greater than 80% of those with standard-risk disease (non-disseminated and near or gross total resection) and greater than 65% of those with high-risk disease (residual tumor ≥1.5 cm,2 evidence of disseminated disease) are expected to be long-term survivors of the disease.2–5 This improvement in outcome has led to an increased focus on improving health-related quality of life in the developing child and adult survivor of medulloblastoma. Recent treatment strategies for medulloblastoma are designed to decrease long-term adverse outcomes while maintaining or even improving survival outcomes.