Development of crizotinib, a rationally designed tyrosine kinase inhibitor for non‐small cell lung cancer
Bibliographic record
Abstract
Non-small cell lung cancer (NSCLC) is the number one cause of global mortality. Despite aggressive treatment, the prognosis is dismal. Patients with advanced NSCLC have a median survival of 4 months from the time of diagnosis. Fortunately, molecularly based approaches to drug discovery have yielded a tyrosine kinase inhibitor, crizotinib, which significantly prolongs median progression-free survival in a subset of patients. Although initial clinical trial results demonstrate crizotinib has a promising role to play in NSCLC treatment, development of resistance leaves much to be elucidated about how to effectively combat this deadly disease. In this review, we follow the discovery and development of crizotinib from bench to bedside and provide an example of successful bottom-up drug design. Then, we explore the clinical trial results that fast-tracked its eventual use as a frontline therapy for sensitive NSCLC patients and the development of resistance. Lastly, we discuss the potential for future uses of crizotinib both within and beyond NSCLC.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| 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".