In silico analysis of hypoxia activated prodrugs in combination with anti angiogenic therapy through nanocell delivery
Bibliographic record
Abstract
Tumour hypoxia is a well-studied phenomenon with implications in cancer progression, treatment resistance, and patient survival.While a clear adverse prognosticator, hypoxia is also a theoretically ideal target for guided drug delivery.This idea has lead to the development of hypoxia-activated prodrugs (HAPs): a class of chemotherapeutics which remain inactive in the body until metabolized within hypoxic regions.In theory, these drugs have the potential for increased tumour selectivity and have therefore been the focus of numerous preclinical studies.Unfortunately, HAPs have had mixed results in clinical trials, necessitating further study in order to harness their therapeutic potential.One possible avenue for the improvement of HAPs is through the selective application of anti angiogenic agents (AAs) to improve drug delivery.Such techniques have been used in combination with other conventional chemotherapeutics to great effect in many studies.A further benefit is theoretically achieved through nanocell administration of the combination, though this idea has not been the subject of any experimental or mathematical studies to date.In the following, a mathematical model is outlined and used to compare the predicted efficacies of separate vs. nanocell administration for AAs and HAPs in tumours.The model is experimentally motivated, both in mathematical form and parameter values.Preliminary results of the model are highlighted throughout which qualitatively agree with existing experimental evidence.The novel prediction of our model is an improvement in the efficacy of AA/HAP combination therapies when administered through nanocells as opposed to separately.While this study specifically models treatment on glioblastoma, similar analyses could be performed for other vascularized tumours, making the results potentially applicable to a range of tumour types. Author summaryTumour hypoxia is a well-documented phenomenon with adverse effects for the progression of the cancer.Accordingly, various therapeutic strategies have emerged in recent years to combat its effects.Herein, we present an experimentally-motivated mathematical model used to assess the feasibility of the therapeutic combination of anti angiogenic agents with hypoxia-activated prodrugs.Analysis of the combination therapy shows that
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".