Blood‐based proteomic profiling reveals context‐dependent changes in BCL2‐associated signaling during taxane therapy in breast cancer patients

FEBS Open Bio

卷:16

Research Article

Saira Munshani¹  Eiman Y. Ibrahim¹  Rozalyn L. Rodwin²  Leah M. Ferrucci³  Kim Blenman^4,5  Maryam Lustberg⁴  Barbara E. Ehrlich¹ 

[1] Department of Chronic Disease Epidemiology and Yale Cancer Center, Yale School of Public Health, New Haven, CT, USA

[2] Department of Pediatrics (Hematology/Oncology), Yale School of Medicine, New Haven, CT, USA

[3] Department of Medicine (Medical Oncology), Yale School of Medicine, New Haven, CT, USA

[4] Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA

[5] Department of Computer Science, School of Engineering and Applied Science, Yale University, New Haven, CT, USA

关键词: apoptosis;    breast cancer;    calcium signaling;    paclitaxel;    senescence;   

DOI  :  10.1002/2211-5463.70239

 received in 2025-10-27, accepted in 2026-03-16,  发布年份 2026

来源: Wiley

【 摘 要 】

The quality of life for many cancer survivors is compromised due to severe, long‐lasting side effects of chemotherapy. As part of a pilot, prospective, non‐interventional study to examine the side effects of chemotherapy in breast cancer patients, we examined the change in protein expression in blood collected from patients before and after treatment with taxanes for 12 weeks. Protein expression was measured with reverse phase proteomic arrays (RPPA), which revealed divergent changes in apoptosis, senescence, and calcium signaling‐related proteins depending on treatment setting (neoadjuvant vs. adjuvant). The largest change identified was BCL2 (B‐cell lymphoma 2), a founding member of the BCL2 family of proteins that regulate apoptosis. Other proteins regulated by BCL2, including RB1 (retinoblastoma protein 1) and NLRP3 (NLR family pyrin domain containing 3) changed significantly over the course of treatment. These differences are consistent with intracellular calcium signaling dysregulation and activation of stress‐response pathways that overlap with senescent‐associated secretory phenotype (SASP)‐like signaling, which has been implicated in cancer recurrence. To contextualize these observations, we generated Kaplan–Meier survival curves using publicly available proteomics data from The Cancer Proteome Atlas (TCPA). This work aims to demonstrate how blood‐based proteomics can serve as a non‐invasive method to monitor systemic physiological shifts during cancer therapy, offering a framework for generating hypotheses about chemotherapy timing and long‐term outcomes.

【 授权许可】

CC BY   
© 2026 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

【 图 表 】

Fig. 10

Fig. 2

Figure 1. Overview of the experimental system.