التفاصيل البيبلوغرافية
| العنوان: |
Combined PI3K Inhibitor and Eribulin Enhances Anti-Tumor Activity in Preclinical Models of Paclitaxel-Resistant, PIK3CA-Mutated Endometrial Cancer. |
| المؤلفون: |
Jeong, Yeong Gyu, Katuwal, Nar Bahadur, Kang, Min Sil, Ghosh, Mithun, Hong, Sa Deok, Park, Seong Min, Kim, Seul-Gi, Kim, Tae Hoen, Moon, Yong Wha |
| المصدر: |
Cancers; Oct2023, Vol. 15 Issue 19, p4887, 16p |
| مصطلحات موضوعية: |
THERAPEUTIC use of antineoplastic agents, CELL differentiation, REVERSE transcriptase polymerase chain reaction, GENETIC mutation, ANIMAL experimentation, LOWE'S syndrome, WESTERN immunoblotting, APOPTOSIS, CELLULAR signal transduction, EPITHELIAL-mesenchymal transition, CELL survival, T-test (Statistics), ENDOMETRIAL tumors, ERIBULIN, DESCRIPTIVE statistics, RESEARCH funding, ESTERASES, PACLITAXEL, CELL lines, DRUG resistance in cancer cells, MICE, PHARMACODYNAMICS, CHEMICAL inhibitors |
| مستخلص: |
Simple Summary: Paclitaxel-based chemotherapy is the standard front-line therapy for advanced or metastatic endometrial cancer. However, paclitaxel resistance eternally develops. Based on the high prevalence of PIK3CA mutation, reaching 50%, in endometrial cancer, we preclinically investigated the effectiveness of a combination of a PI3K inhibitor with eribulin, a post-paclitaxel therapy for breast cancer, in treating paclitaxel-resistant, PIK3CA-mutated endometrial cancer. Based on our in vitro and in vivo results, we suggest that paclitaxel resistance is associated with the activation of the PIK3/AKT pathway in PIK3CA-mutated endometrial cancer, and the combination of a PI3K inhibitor and eribulin merits further clinical investigation. Endometrial cancer stands as the predominant gynecological malignancy in developed nations. For advanced or recurrent disease, paclitaxel-based chemotherapy is the standard front-line therapy. However, paclitaxel resistance eternally develops. Based on the high prevalence of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation, reaching 50%, in endometrial cancer, we preclinically investigated the effectiveness of a combination of a phosphatidylinositol 3-kinase (PI3K) inhibitor with eribulin, a post-paclitaxel therapy for breast cancer, in treating paclitaxel-resistant, PIK3CA-mutated endometrial cancer. We generated paclitaxel-resistant cell lines from PIK3CA-mutated endometrial cancer cell lines by gradually increasing the concentration of paclitaxel in cell cultures. We observed that the PI3K/AKT and epithelial–mesenchymal transition (EMT) pathways in paclitaxel-resistant cells were significantly upregulated compared with those in parental cells. Then, we demonstrated that the combination of alpelisib (a PI3K inhibitor) and eribulin more effectively suppressed the cellular growth of paclitaxel-resistant cells in in vitro and in vivo xenograft models. Mechanistically, we demonstrated that the effect of the combination could be enhanced by inhibiting both the PI3K/AKT and EMT pathways. Therefore, we suggest that paclitaxel resistance is associated with the activation of the PIK3/AKT pathway in PIK3CA-mutated endometrial cancer, and the combination of a PI3K inhibitor and eribulin merits further clinical investigation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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