scholarly journals Alpelisib Exhibits a Synergistic Effect with Pyrotinib and Reverses Acquired Pyrotinib Resistance in HER2+ Breast Cancer

Author(s):  
Hao Chen ◽  
Yuhao Si ◽  
Jialiang Wen ◽  
Chunlei Hu ◽  
Erjie Xia ◽  
...  

Abstract Background: Human epidermal growth factor receptor 2 (HER2) plays a vital role in breast cancer progression in patients who overexpress HER2, thus promoting the rapid progress of targeted drugs development and therapy strategies advancement targeting this gene. Pyrotinib, approved in clinical by the Chinese State Drug Administration, is a novel pan-ErbB kinase inhibitor and exhibits better efficacy than lapatinib. Alpelisib is a selective PI3K p110α inhibitor approved for application in HR+, HER2-, PIK3CA mutated breast cancers. We assumed that combining pyrotinib with alpelisib worked better than single-drug treatment.Methods: We performed the drug combination assay to evaluate the combination index (CI) of pyrotinib and alpelisib in HER2+ breast cancer cell lines. Cell functional assays, RT-qPCR (Real Time-Quantitative Polymerase Chain Reaction) and western blotting were performed to elucidate the combined efficacy of two drugs and explore the underlying mechanism. Then we established the acquired pyrotinib resistant HER2+ breast cancer cell lines and evaluate the combined efficacy of two drugs in pyrotinib resistant cells and explore the potential mechanisms.Results: Our data exhibited that a combination of alpelisib and pyrotinib showed a synergistic effect in HER2+ breast cancer by enhancing cell proliferation and migration decrease, G0-G1 cell cycle arrest, and apoptosis rate increase. Additionally, alpelisib combined with pyrotinib showed a tremendous synergistic effect in acquired pyrotinib resistant cells.Conclusions: Our results provided the preclinical evidence that a combination of pyrotinib and alpelisib as an effective therapeutic strategy in treating HER2+ breast cancer, whether patients were sensitive or resistant to pyrotinib treatment.

2015 ◽  
Vol 18 (4) ◽  
pp. 329 ◽  
Author(s):  
Sonia Ávila-Arroyo ◽  
Gema Santamaría Nuñez ◽  
Luis Francisco García-Fernández ◽  
Carlos M. Galmarini

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 348 ◽  
Author(s):  
Julie Lafontaine ◽  
Jean-Sébastien Boisvert ◽  
Audrey Glory ◽  
Sylvain Coulombe ◽  
Philip Wong

Cancer therapy has evolved to a more targeted approach and often involves drug combinations to achieve better response rates. Non-thermal plasma (NTP), a technology rapidly expanding its application in the medical field, is a near room temperature ionized gas capable of producing reactive species, and can induce cancer cell death both in vitro and in vivo. Here, we used proliferation assay to characterize the plasma sensitivity of fourteen breast cancer cell lines. These assays showed that all tested cell lines were sensitive to NTP. In addition, a good correlation was found comparing cell sensitivity to NTP and radiation therapy (RT), where cells that were sensitive to RT were also sensitive to plasma. Moreover, in some breast cancer cell lines, NTP and RT have a synergistic effect. Adding a dose of PARP-inhibitor olaparib to NTP treatment always increases the efficacy of the treatment. Olaparib also exhibits a synergistic effect with NTP, especially in triple negative breast cancer cells. Results presented here help elucidate the position of plasma use as a potential breast cancer treatment.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14566-e14566
Author(s):  
S. E. Witta ◽  
V. Franekova ◽  
K. Yoshida ◽  
I. Igolnikov ◽  
B. Frederick ◽  
...  

e14566 Background: We previously demonstrated the synergistic effect of the histone deacetylase inhibitor SNDX-275 and gefitinib in non-small cell lung cancer (NSCLC) cell lines lacking E-cadherin expression. We evaluated the combination effect of SNDX- 275 with erlotinib or lapatinib in lung, head and neck (H&N) and breast cancer cell lines resistant to erlotinib or lapatinib(IC50> 1uM) and expressing Her2. Methods: This study included 10 H&N and 17 NSCLC cell lines, 2 breast cancer cell lines with expressing Her2 (SK BR3, MCF7) and one lacking Her2 expression, MDA-MB231. Cell lines were incubated for 5 days with increasing concentrations (0.16, 1 and 6μM) of SNDX-275, lapatinib and erlotinib alone or in combination. The growth inhibitory effect was analyzed with MTT assay. The combination drug effect was evaluated using CalcuSyn (Cambridge, UK). E-cadherin and Her2 expression was evaluated using microarray analysis and RT-PCR. Her2 was considered positive if the relative expression was >300 by RT-PCR. Protein expression was analyzed with western blots. Results: Among the 17 NSCLC and 10 H&N cell lines 16 (12 NSCLC and 4 H&N) had positive Her2 RNA expression. 2 NSCLC (A549, H1703) and 2 H&N (UMSCC10, UMSCC19) were resistant to erlotinib or lapatinib (IC50>1μM). The 2 breast cancer cell lines 2, MCF7 and MDA-MB-321, were resistant to erlotinib and lapatinib. SNDX-275 increased the expression of E-cadherin in 5 of the 6 cell lines selected (A549, H1703, UMSCC19, MCF7 and MDA- MB-321). Synergistic effect of SNDX-275 1μM and lapatinib 1μM was detected in the MCF7, UMSCC10, UMSCC19 cell lines (Combination Index, CI: 0.09, 0.9, 0.67; respectively), while SNDX-275 1μM and erlotinib 1μM were synergistic in MCF7, MDA-MB-321, H1703 and A549 (CI: 0.2, 0.95, 0.58, 0.32; respectively). Conclusions: The combination of SNDX-275 and erlotinib or lapatinib is active in breast, NSCLC, H&N cell lines resistant to either drug alone. [Table: see text]


2013 ◽  
Vol 42 (4) ◽  
pp. 1263-1270 ◽  
Author(s):  
TONI IBRAHIM ◽  
CHIARA LIVERANI ◽  
LAURA MERCATALI ◽  
EMANUELE SACANNA ◽  
MICHELE ZANONI ◽  
...  

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