Combination Therapy with Reovirus and ATM Inhibitor Enhances Cell Death and Virus Replication in Canine Melanoma
Bibliographic record
Abstract
Oncolytic virotherapy using reovirus is a promising new anti-cancer treatment with potential for use in humans and dogs. Because reovirus monotherapy shows limited efficacy in human and canine cancer patients, the clinical development of a combination therapy is necessary. To identify candidate components of such a combination, we screened a 285-compound drug library for those that enhanced reovirus cytotoxicity in a canine melanoma cell line. Here, we show that exposure to an inhibitor of the ataxia telangiectasia mutated protein (ATM) enhances the oncolytic potential of reovirus in five of six tested canine melanoma cell lines. Specifically, the ATM inhibitor potentiated reovirus replication in cancer cells along with promoting the lysosomal activity, resulting in an increased proportion of caspase-dependent apoptosis and cell cycle arrest at G2/M compared to those observed with reovirus alone. Overall, our study suggests that the combination of reovirus and the ATM inhibitor may be an attractive option in cancer therapy.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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) | 0.001 | 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".