Radiosensitization with combined use of olaparib and PI-103 in triple-negative breast cancer

Abstract The use of aspirin has been associated with reduced breast cancer risk, but it is litter known if aspirin overcomes chemoresistance in triple-negative breast cancer (TNBC). Herein, we demonstrated that changes in the expression of Yes-associated protein (YAP) and β-catenin might be a promising predictive biomarker for neoadjuvant chemotherapy sensitivity in TNBC patients. Inhibition of YAP or β-catenin enhanced the cytotoxicity of the anti-microtubule agents docetaxel and vinorelbine against drug-resistant TNBC cells as well as the sensitivity of these cells to the agents in vitro and in vivo. Interestingly, aspirin not only significantly inhibited the growth of TNBC cells, but also attenuated YAP and β-catenin expression by upregulating the E3 ubiquitin ligase β-TrCP to abolished docetaxel and vinorelbine resistance. The combination of aspirin and docetaxel or vinorelbine remarkably inhibited the growth of drug-resistant TNBC cells in vitro and in vivo. Moreover, TNBC patients with high YAP and/or β-catenin expression had a higher risk of relapse or mortality than patients with low YAP and/or β-catenin expression. Collectively, our study discovered a novel role of aspirin based on its anticancer effect, and put forward some possible mechanisms of chemoresistance in TNBC. The combined use of aspirin and anti-microtubule drugs presented several promising therapeutic approaches for TNBC treatment.

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Combined use of apatinib mesylate and vinorelbine versus vinorelbine alone in recurrent or metastatic triple-negative breast cancer: study protocol for a randomized controlled clinical trial

Trials ◽

10.1186/s13063-020-04342-x ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Shuo Wu ◽

Liang Zhang ◽

Huan Li ◽

Junnan Xu ◽

Cui Jiang ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Triple Negative Breast Cancer ◽

Study Protocol ◽

Triple Negative ◽

Controlled Clinical Trial ◽

Randomized Controlled Clinical Trial ◽

Randomized Controlled ◽

Breast Cancer Study ◽

Combined Use

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MET and FASN as Prognostic Biomarkers of Triple Negative Breast Cancer: A Systematic Evidence Landscape of Clinical Study

Frontiers in Oncology ◽

10.3389/fonc.2021.604801 ◽

2021 ◽

Vol 11 ◽

Author(s):

Weihua Jiang ◽

Xiao-Liang Xing ◽

Chenguang Zhang ◽

Lina Yi ◽

Wenting Xu ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Fatty Acid Synthase ◽

Triple Negative ◽

Predictive Ability ◽

Pathological Characteristic ◽

Positive Expression ◽

Combined Use ◽

Mesenchymal Epithelial Transition Factor ◽

Mesenchymal Epithelial Transition

BackgroundTo know the expression of Mesenchymal–Epithelial Transition factor (MET) and Fatty Acid Synthase (FASN) in Triple Negative Breast Cancer (TNBC) patients, as well as its relationship with clinical pathological characteristic and prognosis.Methodswe used immunohistochemistry staining to detect the expression of MET and FASN for those 218 TNBC patients, and analyze their relationship with the clinical pathological characteristic and prognosis.Results130 and 65 out of 218 TNBC patients were positive for MET in the cancer and adjacent tissues respectively. 142 and 30 out of 218 TNBC patients were positive for FASN in the cancer and adjacent tissues respectively. Positive expression of MET and FASN were significantly correlated with lymph node metastasis, pathological TNM, and pathological Stage. In addition, the positive expression of MET and FASN were correlated with recurrence and metastasis. The combined use of MET and FASN can better predict the survival condition.ConclusionsOur results indicated that MET and FASN showed good predictive ability for TNBC. Combined use of MET and FASN were recommended in order to make a more accurate prognosis for TNBC.

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Aspirin attenuates YAP and β-catenin expression by promoting β-TrCP to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13099 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13099-e13099

Author(s):

Ji Ma ◽

Hongwei Xia ◽

Zhenhai Fan ◽

Qiulin Tang ◽

Tao Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Predictive Biomarker ◽

Drug Resistant ◽

Combined Use ◽

And Function

e13099 Background: YAP and β-catenin play critical roles in the carcinogenesis of several cancers, but their functions in chemoresistance remain unclear in triple-negative breast cancer (TNBC). Herein, we examined the expression and function of the two proteins in the chemoresistance of TNBC. Methods: We examined the expression levels of YAP and β-catenin in TNBC samples by immunohistochemistry (IHC) and their roles in prognosis. Dynamic changes in the two proteins in TNBC tissues were determined by RT-PCR. CCK-8 assays, colony formation assays, flow cytometry, migration assays and nude mouse models were used to investigate the functions of YAP and β-catenin in drug-resistant TNBC cells. The involved signalling pathways were detected by western blot assays. Results: TNBC patients with high YAP and/or β-catenin expression had a higher risk of relapse or mortality than patients with low YAP and/or β-catenin expression, and changes in the expression of the two proteins might be a promising predictive biomarker for neoadjuvant chemotherapy sensitivity. Inhibition of YAP or β-catenin enhanced the cytotoxicity of the anti-microtubule agents docetaxel and vinorelbine against TNBC cells in vitro and in vivo. Moreover, YAP and β-catenin were upregulated in docetaxel- or vinorelbine-resistant TNBC cells, while inhibition of YAP or β-catenin enhanced the sensitivity of drug-resistant cells. Interestingly, aspirin, a kind of acetylsalicylic acid, reversed the drug resistance of cells and in combination with aspirin and docetaxel or vinorelbine significantly inhibited the growth of drug-resistant TNBC cells. The involved mechanism is that aspirin impaired YAP or β-catenin expression by upregulating the E3 ubiquitin ligase β-TrCP. Conclusions: Both YAP and β-catenin act as key biomarkers of prognosis and anti-microtubule drug resistance in TNBC, and the combined use of aspirin and anti-microtubule drugs inhibits YAP and β-catenin, presenting several promising therapeutic approaches for TNBC treatment.

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Combined use of arginase and dichloroacetate exhibits anti-proliferative effects in triple negative breast cancer cells

Journal of Pharmacy and Pharmacology ◽

10.1111/jphp.13033 ◽

2018 ◽

Vol 71 (3) ◽

pp. 306-315 ◽

Cited By ~ 8

Author(s):

Angela Verma ◽

Yau-Min Lam ◽

Yun-Chung Leung ◽

Xiaohui Hu ◽

Xin Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Combined Use

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Combining PD-1/PD-L1 inhibitor and PARP inhibitor: a new perspective on the treatment of triple negative breast cancer

Trends in Immunotherapy ◽

10.24294/ti.v5.i2.1.1372 ◽

2021 ◽

Vol 5 (2.1) ◽

pp. 24

Author(s):

Ruilian Xie

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Molecular Mechanisms ◽

Triple Negative ◽

Parp Inhibitor ◽

Parp Inhibitors ◽

Research Progress ◽

Survival Prognosis ◽

Combined Use ◽

New Perspective

Compared with other types of breast cancer, triple negative breast cancer has a poor survival prognosis due to its high aggressiveness and lack of effective therapeutic targets. Immune checkpoint (PD-1/PD-L1 and CTL-4) inhibitors have emerged as a breakthrough therapy in the treatment in various metastatic cancers. PARP inhibitors promote DNA damage in tumor cells, not only promoting immune initiation through a series of molecular mechanisms, but also leading to adaptive upregulation of programmed death ligand 1 (PD-L1) expression. Therefore, the combination of the two inhibitors can improve the efficacy of tumor treatment. We reviewed the research progress of their combined use in triple negative breast cancer, and put forward relevant ideas for further development, hoping to find the best treatment mode of the combined use of the two.

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