7. PD-L1 in triple negative breast cancer – optimal testing for therapeutic efficacy

Pathology ◽  
2020 ◽  
Vol 52 ◽  
pp. S135
Author(s):  
J. Yeong ◽  
Z.-L. Chow ◽  
T.J. Tan ◽  
H. Li ◽  
A. Seet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Therapeutic Efficacy ◽  
Triple Negative

scholarly journals Biomimetic oxygen delivery nanoparticles for enhancing photodynamic therapy in triple-negative breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hanyi Fang ◽  
Yongkang Gai ◽  
Sheng Wang ◽  
Qingyao Liu ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Photodynamic Therapy ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Oxygen Delivery ◽  
Therapeutic Efficacy ◽  
Triple Negative ◽  
Oxygen Solubility ◽  
Post Injection

Abstract Background Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm–HSA–ICG–PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts. Results The size of the CCm–HSA–ICG–PFTBA was 131.3 ± 1.08 nm. The in vitro 1O2 and ROS concentrations of the CCm–HSA–ICG–PFTBA group were both significantly higher than those of the other groups (P < 0.001). In vivo fluorescence imaging revealed that the best time window was at 24 h post-injection of the CCm–HSA–ICG–PFTBA. Both in vivo 18F-FMISO PET imaging and ex vivo immunofluorescence staining results exhibited that the tumor hypoxia was significantly improved at 24 h post-injection of the CCm–HSA–ICG–PFTBA. For in vivo PDT treatment, the tumor volume and weight of the CCm–HSA–ICG–PFTBA with NIR group were both the smallest among all the groups and significantly decreased compared to the untreated group (P < 0.01). No obvious biotoxicity was observed by the injection of CCm–HSA–ICG–PFTBA till 14 days. Conclusions By using the high oxygen solubility of perfluorocarbon (PFC) and the homologous targeting ability of cancer cell membranes, CCm–HSA–ICG–PFTBA can target tumor tissues, mitigate the hypoxia of the tumor microenvironment, and enhance the PDT efficacy in TNBC xenografts. Furthermore, the HSA, ICG, and PFC are all FDA-approved materials, which render the nanoparticles highly biocompatible and enhance the potential for clinical translation in the treatment of TNBC patients.

scholarly journals Biomimetic Oxygen Delivery Nanoparticles for Enhancing Photodynamic Therapy in Triple-negative Breast Cancer

2021 ◽  
Author(s):  
Hanyi Fang ◽  
Yongkang Gai ◽  
Sheng Wang ◽  
Qingyao Liu ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Photodynamic Therapy ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Oxygen Delivery ◽  
Therapeutic Efficacy ◽  
Triple Negative ◽  
Oxygen Solubility ◽  
Post Injection

Abstract Background Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm-HSA-ICG-PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts. Results The size of the CCm-HSA-ICG-PFTBA was 131.3 ± 1.08 nm. The in vitro 1O2 and ROS concentrations of the CCm-HSA-ICG-PFTBA group were both significantly higher than those of the other groups (P < 0.001). In vivo fluorescence imaging revealed that the best time window was at 24 h post-injection of the CCm-HSA-ICG-PFTBA. Both in vivo 18F-FMISO PET imaging and ex vivo immunofluorescence staining results exhibited that the tumor hypoxia was significantly improved at 24 h post-injection of the CCm-HSA-ICG-PFTBA. For in vivo PDT treatment, the tumor volume and weight of the CCm-HSA-ICG-PFTBA with NIR group were both the smallest among all the groups and significantly decreased compared to the untreated group (P < 0.01). No obvious biotoxicity was observed by the injection of CCm-HSA-ICG-PFTBA till 14 days. Conclusions By using the high oxygen solubility of perfluorocarbon (PFC) and the homologous targeting ability of cancer cell membranes, CCm-HSA-ICG-PFTBA can target tumor tissues, mitigate the hypoxia of the tumor microenvironment, and enhance the PDT efficacy in TNBC xenografts. Furthermore, the HSA, ICG, and PFC are all FDA-approved materials, which render the nanoparticles highly biocompatible and enhance the potential for clinical translation in the treatment of TNBC patients.

scholarly journals Preclinical Activity Profile and Therapeutic Efficacy of the HSP90 Inhibitor Ganetespib in Triple-Negative Breast Cancer

2013 ◽  
Vol 20 (2) ◽  
pp. 413-424 ◽  
Author(s):  
David A. Proia ◽  
Chaohua Zhang ◽  
Manuel Sequeira ◽  
John-Paul Jimenez ◽  
Suqin He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Therapeutic Efficacy ◽  
Triple Negative ◽  
Hsp90 Inhibitor ◽  
Activity Profile

scholarly journals LIFR inhibition enhances the therapeutic efficacy of HDAC inhibitors in triple negative breast cancer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mengxing Li ◽  
Suryavathi Viswanadhapalli ◽  
Bindu Santhamma ◽  
Uday P. Pratap ◽  
Yiliao Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Therapeutic Efficacy ◽  
Histone Deacetylase Inhibitors ◽  
Triple Negative ◽  
Hdac Inhibitors ◽  
Rna Seq ◽  
Leukemia Inhibitory Factor Receptor ◽  
Targeted Inhibition

AbstractHistone deacetylase inhibitors (HDACi) are identified as novel therapeutic agents, however, recent clinical studies suggested that they are marginally effective in treating triple negative breast cancer (TNBC). Here, we show that first-in-class Leukemia Inhibitory Factor Receptor (LIFRα) inhibitor EC359 could enhance the therapeutic efficacy of HDACi against TNBC. We observed that both targeted knockdown of LIFR with CRISPR or treatment with EC359 enhanced the potency of four different HDACi in reducing cell viability, cell survival, and enhanced apoptosis compared to monotherapy in TNBC cells. RNA-seq studies demonstrated oncogenic/survival signaling pathways activated by HDACi were attenuated by the EC359 + HDACi therapy. Importantly, combination therapy potently inhibited the growth of TNBC patient derived explants, cell derived xenografts and patient-derived xenografts in vivo. Collectively, our results suggest that targeted inhibition of LIFR can enhance the therapeutic efficacy of HDACi in TNBC.

Delivery of novel Coumarin-dihydropyrimidinone conjugates through mixed polymeric nanoparticle to potentiate therapeutic efficacy against triple-negative breast cancer

2021 ◽  
Author(s):  
Avijit Ghosh ◽  
Priyanka Upadhyay ◽  
Sushmita Sarker ◽  
Shaswati Das ◽  
Mousumi Bhattacharjee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Therapeutic Efficacy ◽  
Triple Negative ◽  
Therapeutic Options ◽  
Polymeric Nanoparticle

Till date most of the accessible therapeutic options are virtually non-responsive towards Triple-negative breast cancer (TNBC) due to their highly aggressive and metastatic nature. Interestingly, chemotherapy reacts soundly in many...

Targeting EGFR of triple-negative breast cancer enhances the therapeutic efficacy of paclitaxel- and cetuximab-conjugated nanodiamond nanocomposite

2019 ◽  
Vol 86 ◽  
pp. 395-405 ◽  
Author(s):  
Wei-Siang Liao ◽  
Yu Ho ◽  
Yu-Wei Lin ◽  
Emmanuel Naveen Raj ◽  
Kuang-Kai Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Therapeutic Efficacy ◽  
Triple Negative
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