Abstract IA006: Progress, pitfalls and promise: the journey to effective and well tolerated DNA damage response inhibitor combinations in the clinic
Bibliographic record
Abstract
A mounting body of evidence now indicates that poly(ADP-ribose) polymerase (PARP) inhibitors have the potential to be used as a foundation for both monotherapy and combination strategies across a wide spectrum of molecular backgrounds and tumor types. There are multiple promising combination therapeutic strategies, such as those with other DNA damage response (DDR) inhibitors such as ATR inhibitors, immune checkpoint inhibitors, and non-DDR-targeted agents that induce "chemical BRCAness". Despite promising efficacy data, several of the combinations have been hampered by supra-additive toxicities, restricting the combination of full monotherapy doses and schedules of component drugs. I will discuss the progress, pitfalls and promise of different classes of DNA damage response (DDR) inhibitor combinations in the clinic, and discuss potential clinical strategies to develop effective and well tolerated combinations to target PARP inhibitor resistance and to widen the application of DDR agents beyond approved indications Citation Format: Timothy A. Progress, pitfalls and promise: the journey to effective and well tolerated DNA damage response inhibitor combinations in the clinic. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA006
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 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 | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.005 | 0.006 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.006 |
| Insufficient payload (model declined to judge) | 0.018 | 0.010 |
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".