Abstract A119: Investigating PIK3CA mutational status on cisplatin and radiation sensitivity in cervical cancer cell lines: Implications for PI3K inhibitor therapy
Bibliographic record
Abstract
Abstract The phosphatidylinositol-3 kinase (PI3K)/AKT/ mTOR signaling pathway is activated in many different human cancers. Activation is frequently mediated by “hotspot” mutations including E542K, E545K and H1047R in the PIK3CA gene, which encodes the catalytic subunit of PI3Kα. We previously reported PIK3CA mutation in patients with early stage (IB/II) cervical cancer was associated with poor survival (McIntyre et al. Gynecol Oncol. 2013, 128(3): 409-14). The purpose of this study was to determine whether PIK3CA mutation renders cervical cancer cells more resistant to conventional therapy (cisplatin chemotherapy and/or radiation), and whether PI3K inhibition enhances cell kill and/or reverse this phenotype. Here, we report that the cervical cancer cell line CaSki, which expresses the PIK3CA-E545K mutation, is more resistant to cisplatin than cervical cancer cells with wild-type PIK3CA. To validate our findings, we depleted endogenous PIK3CA from HeLa cells using shRNA and stably expressed either shRNA resistant wild-type PIK3CA or PIK3CA-E545K. Cells expressing PIK3CA-E545K were more resistant to cisplatin and cisplatin plus ionizing radiation than cells expressing either wild-type PIK3CA or lacking PIK3CA. Preliminary results also suggest that cells expressing PIK3CA-E545K have an enhanced migratory phenotype. We are currently testing whether treatment with the PI3K inhibitor GDC-0941 restores sensitivity to cisplatin and reverts this aggressive phenotype. Together, these experiments will determine whether inhibition of the PI3K pathway in cervical cancers with PIK3CA activating mutation has potential for therapeutic benefit. Citation Format: ARJUMAND WANI, COLE MERRY, CHEN WANG, SHUJUAN FANG, ELIZABETH KORNAGA, Jb MCINTYRE, PRAFULL GHATAGE, MARTIN KöBEL, CORINNE M. DOLL, SUSAN P. LEES-MILLER. Investigating PIK3CA mutational status on cisplatin and radiation sensitivity in cervical cancer cell lines: Implications for PI3K inhibitor therapy. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A119.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".