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High-risk childhood leukemia has a poor prognosis because of treatment failure and toxic side effects of therapy. Drug encapsulation into liposomal nanocarriers has shown clinical success at improving biodistribution and tolerability of chemotherapy. However, enhancements in drug efficacy have been limited because of a lack of selectivity of the liposomal formulations for the cancer cells.
The mitogen-activated protein kinase (MAPK) pathway signaling pathway is one of the most commonly mutated pathways in human cancers. In particular, BRAF alterations result in constitutive activation of the rapidly accelerating fibrosarcoma-extracellular signal-regulated kinase-MAPK significant pathway, leading to cellular proliferation, survival, and dedifferentiation.
A pilot clinical study, led in Australia by a The Kids Research Institute Australia and Perth Children's Hospital researcher, has found an immunotherapy drug can dramatically increase survival rates for babies with a rare form of leukaemia, paving the way for a major international clinical trial.
This review identifies challenges and barriers to successful development of drugs in neuro-oncology trials at the preclinical, clinical and translational stages that we believe has contributed to poor outcomes for patients over the last 30 years.
KMT2A-rearranged acute lymphoblastic leukemia (ALL) in infants is an aggressive disease with 3-year event-free survival below 40%. Most relapses occur during treatment, with two thirds occurring within 1 year and 90% within 2 years after diagnosis. Outcomes have not improved in recent decades despite intensification of chemotherapy.
In children, the majority of cases are self-limiting and thus many paediatric patients can be managed conservatively with minimal complications. This varies considerably compared to adult newly diagnosed immune thrombocytopaenia (NDITP) where, in most cases, thrombocytopaenia persists with higher risk of moderate to severe bleeding complications.
Within PF-EPN-A, 1q gain is a marker of poor prognosis, however, it is unclear if within PF-EPN-A additional cytogenetic events exist which can refine risk stratification.
Central nervous system germinomas are treatment-sensitive tumors with excellent survival outcomes. Current treatment strategies combine chemotherapy with radiotherapy (RT) in order to reduce the field and dose of RT. Germinomas originating in the basal ganglia/thalamus have proven challenging to treat given their rarity and poorly defined imaging characteristics. Craniospinal, whole brain, whole ventricle, and focal RT have all been utilized; however, the best treatment strategy remains unclear.
Diffuse intrinsic pontine glioma (DIPG) remains a clinico-radiologic diagnosis without routine tissue acquisition. Reliable imaging distinction between DIPG and other pontine tumors with potentially more favorable prognoses and treatment considerations is essential.
Chemotherapy has historically been the mainstay of cancer treatment, but our understanding of what drives a successful therapeutic response remains limited.