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01-11-2024 | Breast Cancer | Letter to the Editor

Clinical research on triple-negative breast cancer that targets the PIK3CA pathway

Author: Kadri Altundag

Published in: Medical Oncology | Issue 11/2024

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Excerpt

I would like to congratulate Mehrtabar and their colleagues on their publication [1] reviewing impact of microRNA variants on PI3K/AKT signaling in triple-negative breast cancer (TNBC). They come to the conclusion that clarifying the functions of microRNAs (miRs) in modifying the PI3K/AKT signaling pathway will improve our comprehension of the biology of TNBC and reveal possible targets for treatment. Nevertheless, there is a lack of documented clinical data regarding the application of miRS in the treatment of TNBC. Alpelisib (BYL719) is an oral specific PI3Kα inhibitor and it effectively reduces the risk of treatment-related toxic side effects and extends the therapeutic window compared with pan-PI3K inhibitors [2]. Although alpelisib, combined with fulvestrant, was approved by the FDA for treating patients with HR-positive, HER2-negative, PIK3CA mutated advanced or progressive BC, its use in TNBC continues to be explored. A phase I/II trial that enrolled 42 patients with HER2-negative advanced-stage BC (including 12 TNBC patients) demonstrated that alpelisib combined with nab-paclitaxel had good tolerance and encouraging efficacy. Additionally, 40% of patients with PI3KCA mutations had longer PFS than the non-mutated group at 11.9 and 7.5 months, respectively [3]. In summary, PI3K-selective inhibitors have a broad development field and great potential for clinical application, despite not having a license in the TNBC field. As a result, the next clinical trial design may center around the combination of chemotherapy and inhibitors related to the PI3K/AKT/mTOR signaling pathway, with the option to combine immunotherapy with AR, PARP, and CDK4/6 inhibitors to treat TNBC [4]. …
Literature
2.
go back to reference Fritsch C, Huang A, Chatenay-Rivauday C, Schnell C, Reddy A, Liu M, et al. Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014;13:1117–29.CrossRefPubMed Fritsch C, Huang A, Chatenay-Rivauday C, Schnell C, Reddy A, Liu M, et al. Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014;13:1117–29.CrossRefPubMed
3.
go back to reference Sharma P, Abramson VG, O’Dea A, Nye L, Mayer I, Pathak HB, et al. Clinical and biomarker results from phase I/II study of PI3K inhibitor alpelisib plus nab-paclitaxel in HER2-negative metastatic breast cancer. Clin Cancer Res. 2021;27:3896–904.CrossRefPubMedPubMedCentral Sharma P, Abramson VG, O’Dea A, Nye L, Mayer I, Pathak HB, et al. Clinical and biomarker results from phase I/II study of PI3K inhibitor alpelisib plus nab-paclitaxel in HER2-negative metastatic breast cancer. Clin Cancer Res. 2021;27:3896–904.CrossRefPubMedPubMedCentral
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go back to reference Zhang HP, Jiang RY, Zhu JY, Sun KN, Huang Y, Zhou HH, et al. PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer. Breast Cancer. 2024;31:539–51.CrossRefPubMed Zhang HP, Jiang RY, Zhu JY, Sun KN, Huang Y, Zhou HH, et al. PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer. Breast Cancer. 2024;31:539–51.CrossRefPubMed
Metadata
Title
Clinical research on triple-negative breast cancer that targets the PIK3CA pathway
Author
Kadri Altundag
Publication date
01-11-2024
Publisher
Springer US
Published in
Medical Oncology / Issue 11/2024
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-024-02493-4

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