RAS/MAPK inhibition in pediatric gliomas
Bibliographic record
Abstract
Unresectable pediatric low-grade glioma is a chronic disease that can cause significant morbidity in young patients. Historically, treatment has mainly involved chemotherapy, with many patients needing multiple lines of treatment for a recurring/relapsing disease. Orally administered inhibitors targeting the rat sarcoma virus (RAS)/mitogen-activated protein kinase (MAPK) pathway, which is the most frequently altered pathway in this disease, have resulted in a new era in the management and care for these patients. Some drugs have been already approved for specific indications, based on improved response rates in comparison to chemotherapy regimens. In this manuscript, we review the current landscape of RAS/MAPK-inhibitor use in sporadic, pediatric low-grade, and select subsets of high-grade gliomas. We summarize the recently completed trials that led to the approvals, as well as ongoing and upcoming trials investigating upfront use, combinatorial approaches, and newer agents. We highlight some of the unique challenges the neuro-oncology community is facing in this new age of targeted therapies, including a distinct set of toxicities, current unknowns, including the optimal duration of treatment, durability of response, mechanisms of tumor rebound and resistance, and the long-term impact of therapy. We conclude by focusing on some of the needed areas for research and clinical applications relevant to this patient population in the coming decade.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".