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- Title
Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A.
- Authors
Mouron, S.; Bueno, M. J.; Lluch, A.; Manso, L.; Calvo, I.; Cortes, J.; Garcia-Saenz, J. A.; Gil-Gil, M.; Martinez-Janez, N.; Apala, J. V.; Caleiras, E.; Ximénez-Embún, Pilar; Muñoz, J.; Gonzalez-Cortijo, L.; Murillo, R.; Sánchez-Bayona, R.; Cejalvo, J. M.; Gómez-López, G.; Fustero-Torre, C.; Sabroso-Lasa, S.
- Abstract
Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N = 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel. Phosphoproteomics is a promising tool for identifying biomarkers of treatment response in cancer. Here, the authors analyse proteomics profiling of HER2-negative female breast cancer patients and identify potential predictors of paclitaxel response.
- Subjects
PACLITAXEL; CYCLIN-dependent kinases; BREAST cancer; TUBULINS; INDEPENDENT sets; KINASES; MEDICAL screening
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-35065-z