Abstract A186: KIF14 is a novel therapeutic target for ovarian cancer.
Bibliographic record
Abstract
Abstract Introduction: The dismal prognosis associated with ovarian cancers (OvCa) is a consequence of late detection and ineffective strategies to prevent progression. Hence, identification and targeting of genetic events underlying OvCa tumor initiation and progression may have greater potential to achieve cure. Our study of the paediatric eye cancer retinoblastoma revealed mechanisms of cancer initiation and development, where progression is associated with specific genomic aberrations shared among multiple cancers. We identified the novel oncogene KIF14 (kinesin family member 14, chromosome 1q31–1q32), gained in many cancers including retinoblastoma, lung, breast, and ovarian. We demonstrated that KIF14 overexpression in breast and lung cancers is predictive of poor outcome. In normal cells, KIF14 acts during cytokinesis to ensure proper cell division, however its mechanism of action in cancer cells is unknown. Knowledge of the biology of KIF14 in OvCa may therefore define an important therapeutic target. We hypothesize that KIF14 overexpression contributes to OvCa tumorigenesis. Results: Real-time QPCR analysis of primary OvCa tumors demonstrated that KIF14 mRNA is overexpressed in the majority of OvCa tumors studied (111 out of 122 samples), regardless of histological subtype. Close to 30% of serous OvCas display genomic gain of KIF14, with similar gains in early and late stages, suggesting that gain of KIF14 could be an early event in the development of serous OvCa. Multivariate Cox regression analyzes revealed that KIF14 mRNA levels were independently predictive of poor outcome and increased rates of recurrence in serous OvCa patients, demonstrating the value of KIF14 expression as a potential marker for “high risk” serous OvCa patients. Stable in vitro overexpression of KIF14 in OvCa cells increased proliferation and soft agar colony formation, while stable shRNA knockdown of KIF14 decreased proliferation and dramatically reduced soft agar colony formation. In vivo tumor formation is also dependent on KIF14 expression, as KIF14 knockdown significantly reduced subcutaneous xenograft formation by 20-fold. These findings demonstrate the transformed phenotype is dependent on KIF14. Conclusions: KIF14 expression is tumor-specific, can predict poor prognosis, and OvCa cells depend on KIF14 for maintenance of the transformed phenotype. Thus KIF14 overexpression is an oncogenic stimulus in OvCa, pointing to the potential utility of KIF14 expression as a prognostic biomarker, and KIF14 knockdown as a novel therapy to slow or halt OvCa progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A186.
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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) | 0.000 | 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) | 0.000 | 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".