Article
Oncology
Kurt W. Evans, Erkan Yuca, Stephen S. Scott, Ming Zhao, Natalia Paez Arango, Christian X. Cruz Pico, Turcin Saridogan, Maryam Shariati, Caleb A. Class, Christopher A. Bristow, Christopher P. Vellano, Xiaofeng Zheng, Ana Maria Gonzalez-Angulo, Xiaoping Su, Coya Tapia, Ken Chen, Argun Akcakanat, Bora Lim, Debu Tripathy, Timothy A. Yap, Maria Emilia Di Francesco, Giulio F. Draetta, Philip Jones, Timothy P. Heffernan, Joseph R. Marszalek, Funda Meric-Bernstam
Summary: Oxidative phosphorylation is a metabolic vulnerability in triple-negative breast cancer, and inhibiting it with IACS-10759 may enhance efficacy of multiple targeted therapies.
Article
Biochemistry & Molecular Biology
Jun-Ping Shiau, Cheng-Che Wu, Shu-Jyuan Chang, Mei-Ren Pan, Wangta Liu, Fu Ou-Yang, Fang-Ming Chen, Ming-Feng Hou, Shen-Liang Shih, Chi-Wen Luo
Summary: The study found a positive correlation between FAK and VEGFR2 in TNBC patients, and FAK promotes angiogenesis in TNBC cells by regulating VEGFR2 expression. Therefore, targeting FAK could be a potential strategy for TNBC treatment.
Article
Pharmacology & Pharmacy
Ting Yang, Yi-Xin Jiang, Ye Wu, Dong Lu, Rui Huang, Long-Ling Wang, Shi-Qi Wang, Ying-Yun Guan, Hong Zhang, Xin Luan
Summary: Resibufogenin (RBF) derived from Bufo bufonis exhibits anti-tumor effects by inhibiting angiogenesis on human umbilical vein endothelial cells (HUVECs) and in vivo by disrupting VEGFR2 phosphorylation and downstream pathways. RBF shows promising anti-angiogenic effects without obvious toxicity in vivo, suggesting its potential as an anti-angiogenic agent for angiogenesis-related diseases.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Oncology
Bruno de Paula, Rosalind Kieran, Samantha Shui Yuan Koh, Susanne Crocamo, Eliana Abdelhay, Daniel Mun
Summary: Triple-negative breast cancer (TNBC) is associated with a high risk of recurrence and poor prognosis. Previous systemic treatment options were limited to chemotherapy, but now immunotherapy and targeted therapies provide longer-lasting benefits. Treatment resistance due to heterogeneous response is a challenge in TNBC, and induction of senescence by anticancer therapy may lead to dysfunctional and metabolically active cells that foster treatment-resistant repopulation. Targeting senescent cells has shown promise in overcoming resistance, but there are challenges in terms of combination schedules, senescence assessment, specific vulnerabilities, and clinical applicability. This review provides an overview of senescence in TNBC and explores future strategies in senotherapy.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Genetics & Heredity
Justine Marsolier, Pacome Prompsy, Adeline Durand, Anne-Marie Lyne, Camille Landragin, Amandine Trouchet, Sabrina Tenreira Bento, Almut Eisele, Sophie Foulon, Lea Baudre, Kevin Grosselin, Mylene Bohec, Sylvain Baulande, Ahmed Dahmani, Laura Sourd, Eric Letouze, Anne-Vincent Salomon, Elisabetta Marangoni, Leila Perie, Celine Vallot
Summary: The persistence of drug-resistant cancer cells is a major clinical challenge, particularly in triple-negative breast cancer. This study reveals that the repressive histone mark H3K27me3 plays a crucial role in regulating cell fate and chemotherapy tolerance in cancer cells. Manipulating H3K27me3 levels effectively enhances the potential of cancer cells to tolerate chemotherapy and delays tumor recurrence. These findings underscore the importance of understanding chromatin landscapes in shaping cancer cell response to initial therapy.
Article
Biochemistry & Molecular Biology
Lake-Ee Quek, Michelle van Geldermalsen, Yi Fang Guan, Kanu Wahi, Chelsea Mayoh, Seher Balaban, Angel Pang, Qian Wang, Mark J. Cowley, Kristin K. Brown, Nigel Turner, Andrew J. Hoy, Jeff Holst
Summary: This study reveals that glutamine-indispensable triple-negative breast cancer (TNBC) cells rely on a non-canonical glutamine-to-glutamate overflow, which increases TCA cycle fluxes and replenishes TCA cycle intermediates. The coupling of glucose and glutamine catabolism hampers TNBC cells' ability to oxidize glucose when glutamine is limiting.
Article
Gastroenterology & Hepatology
Li Wang, Qihui Zhu, Jitao David Zhang, Yaling Zhang, Xiaoju Ni, Kunlun Xiang, Jiaxi Jiang, Baocun Li, Youjun Yu, Hui Hu, Meifang Zhang, Waikwong Wu, Jing Zeng, Zhipeng Yan, Jieyu Dai, Kai Sun, Xin Zhang, Dongdong Chen, Song Feng, Lisa Sach-Peltason, John A. T. Young, Lu Gao
Summary: A small-molecule cccDNA inhibitor has been discovered that reduces the levels of HBV cccDNA. This provides a potential new approach for the complete cure of patients chronically infected with HBV.
JOURNAL OF HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Keun-Yeong Jeong, Seon Young Park, Min Hee Park, Hwan Mook Kim
Summary: Calcium supply can lead to the degradation of Src protein, reducing the survival signals in triple-negative breast cancer cells, thus showing potential as an anti-cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Dorota Kwapisz
Summary: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and limited treatment options, but it shows higher immunogenicity, tumor-infiltrating lymphocytes (TILs) enrichment, and programmed cell death ligand 1 (PD-L1) expression which make it more suitable for immune checkpoint blockade therapy. Patients with PD-L1-positive TNBC subgroup may benefit the most from immune checkpoint inhibitor (ICI) treatment, and ICI given as first-line treatment in advanced TNBC shows better results than in later lines of treatment. Exciting results have been seen with pembrolizumab in early-stage TNBC, indicating potential approval in (neo)adjuvant settings in the near future.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
Wenwen Geng, Meiling Cao, Ke Dong, Junhua An, Haidong Gao
Summary: Our study revealed that aberrant activation of the mTOR pathway is a characteristic alteration in triple-negative breast cancer (TNBC), but the mTOR pathway inhibitor everolimus is not effective for TNBC patients. We identified that the activation of the ERK pathway is an important mechanism of resistance to everolimus in TNBC cells, and SHOC2 plays a critical role in mediating this pathway. Knockdown of SHOC2 significantly inhibited the activation of the Raf-ERK pathway induced by everolimus. Moreover, interference with SHOC2 expression in combination with everolimus had significant effects on cell cycle progression and apoptosis in vitro experiments.
CANCER BIOLOGY & THERAPY
(2023)
Article
Chemistry, Medicinal
Carine M. Abdelmalek, Zexi Hu, Thales Kronenberger, Jenni Kublbeck, Franziska J. M. Kinnen, Salma S. Hesse, Afsin Malik, Mark Kudolo, Raimund Niess, Matthias Gehringer, Lars Zender, Paula A. Witt-Enderby, Darius P. Zlotos, Stefan A. Laufer
Summary: Anticancer drug conjugates that simultaneously target two receptors may overcome the limitations of current cancer treatments. A series of compounds connecting tamoxifen or endoxifen with the EGFR-inhibitor gefitinib exhibit potent anticancer activity in breast cancer cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Rui Han, Hongxing Yang, Changquan Ling, Lingeng Lu
Summary: In this study, the therapeutic potential of Tiliroside (TS) in triple negative breast cancer (TNBC) was evaluated. The results showed that TS exhibited anti-cancer activity, reduced tumor burden, and improved survival rate in TNBC. Additionally, TS acted as a CAXII inhibitor to suppress TNBC progression.
CANCER CELL INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Maria Grazia Ferraro, Marco Bocchetti, Claudia Riccardi, Marco Trifuoggi, Luigi Paduano, Daniela Montesarchio, Gabriella Misso, Rita Santamaria, Marialuisa Piccolo, Carlo Irace
Summary: Based on strong preclinical evidence, this study focuses on the treatment of challenging indications, such as TNBC, using a novel ruthenium-based metallotherapeutics. An experimental model was used to validate the potential of the liposomal nanoformulation HoThyRu/DOTAP, which effectively delivered the antiproliferative compound AziRu to inhibit TNBC cell growth, migration, and invasion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Jieun Lee
Summary: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer, accounting for 15-20% of cases, with a high rate of recurrence despite chemotherapy. Conventional cytotoxic chemotherapy with anthracyclines and taxanes remains the main treatment option. Achievement of pathologic complete response (pCR) is associated with improved survival outcomes, leading to the shift towards neoadjuvant treatment and investigation of intensified chemotherapy and post-neoadjuvant therapy. This article reviews the current treatment landscape for early TNBC, from standard cytotoxic chemotherapy to immune checkpoint inhibitors, capecitabine, and olaparib.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Oncology
Shengye Jin, Qin Wang, Hao Wu, Da Pang, Shouping Xu
Summary: Biological therapy, particularly oncolytic viruses (OVs), has shown promising therapeutic effects in various cancers, including triple negative breast cancer (TNBC). TNBC, lacking conventional treatment targets, benefits from the emerging concept of OVs for potential treatment options.
BIOMARKER RESEARCH
(2021)
Article
Chemistry, Medicinal
Xing-Dong Lin, Hui-Wen Yang, Shuang Ma, Wei-Wei Li, Chun-Hui Zhang, Wen-Jing Wang, Rong Xiang, Lin-Li Li, Sheng-Yong Yang
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2015)
Article
Chemistry, Medicinal
Xu-Ri Yu, Yun Tang, Wen-Jing Wang, Sen Ji, Shuang Ma, Lei Zhong, Chun-Hui Zhang, Jiao Yang, Xiao-Ai Wu, Zheng-Yan Fu, Lin-Li Li, Sheng-Yong Yang
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2015)
Article
Chemistry, Medicinal
Chun-Hui Zhang, Ming-Wu Zheng, Ya-Ping Li, Xing-Dong Lin, Mei Huang, Lei Zhong, Guo-Bo Li, Rong-Jie Zhang, Wan-Ting Lin, Yan Jiao, Xiao-Ai Wu, Jiao Yang, Rong Xiang, Li-Juan Chen, Ying-Lan Zhao, Wei Cheng, Yu-Quan Wei, Sheng-Yong Yang
JOURNAL OF MEDICINAL CHEMISTRY
(2015)
Article
Chemistry, Medicinal
Xiaoai Wu, Zhen Fang, Bo Yang, Lei Zhong, Qiuyuan Yang, Chunhui Zhang, Shenzhen Huang, Rong Xiang, Takayoshi Suzuki, Lin-Li Li, Sheng-Yong Yang
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2016)
Article
Chemistry, Medicinal
Chun-Hui Zhang, Kai Chen, Yan Jiao, Lin-Li Li, Ya-Ping Li, Rong-Jie Zhang, Ming-Wu Zheng, Lei Zhong, Shen-Zhen Huang, Chun-Li Song, Wan-Ting Lin, Jiao Yang, Rong Xiang, Bing Peng, Jun-Hong Han, Guang-Wen Lu, Yu-Quan Wei, Sheng-Yong Yang
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Medicine, Research & Experimental
Xiaoai Wu, Xiuli Wu, Qizheng Sun, Chunhui Zhang, ShengYong Yang, Lin Li, Zhiyun Jia
Article
Biochemistry & Molecular Biology
Xiao-Yu Qing, Chun-Hui Zhang, Lin-Li Li, Pan Ji, Shuang Ma, Hua-Lin Wan, Ze-Rong Wang, Jun Zou, Sheng-Yong Yang
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2013)
Article
Chemistry, Medicinal
Wei-Wei Li, Xiao-Yan Wang, Ren-Lin Zheng, Heng-Xiu Yan, Zhi-Xing Cao, Lei Zhong, Ze-Rong Wang, Pan Ji, Ling-Ling Yang, Li-Jiao Wang, Yong Xu, Jing-Jing Liu, Jiao Yang, Chun-Hui Zhang, Shuang Ma, Shan Feng, Qi-Zheng Sun, Yu-Quan Wei, Sheng-Yong Yang
JOURNAL OF MEDICINAL CHEMISTRY
(2012)
Article
Chemistry, Medicinal
Jiao Yang, Li-Jiao Wang, Jing-Jing Liu, Lei Zhong, Ren-Lin Zheng, Yong Xu, Pan Ji, Chun-Hui Zhang, Wen-Jing Wang, Xing-Dong Lin, Lin-Li Li, Yu-Quan Wei, Sheng-Yong Yang
JOURNAL OF MEDICINAL CHEMISTRY
(2012)
Article
Biochemical Research Methods
Lei Di-wu, Lin-Li Li, Wen-Jing Wang, Huan-Zhang Xie, Jiao Yang, Chun-Hui Zhang, Qi Huang, Lei Zhong, Shan Feng, Sheng-Yong Yang
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2012)
Letter
Oncology
Z-X Cao, J-J Liu, R-L Zheng, J. Yang, L. Zhong, Y. Xu, L-J Wang, C-H Zhang, B-L Wang, S. Ma, Z-R Wang, H-Z Xie, Y-Q Wei, S-Y Yang
Article
Biochemistry & Molecular Biology
Qi-Zheng Sun, Yong Xu, Jing-Jing Liu, Chun-Hui Zhang, Ze-Rong Wang, Ren-Lin Zheng, Wen-Jing Wang, Lin-Li Li, Sheng-Yong Yang
MOLECULAR DIVERSITY
(2014)
Article
Biochemistry & Molecular Biology
Maya G. Deshmukh, Joseph A. Ippolito, Chun-Hui Zhang, Elizabeth A. Stone, Raquel A. Reilly, Scott J. Miller, William L. Jorgensen, Karen S. Anderson
Summary: This study optimized an existing FDA-approved chemical scaffold, perampanel, to noncovalently bind and inhibit M-pro, achieving IC(50)s in the low-nanomolar range and EC(50)s in the low-micromolar range. The research presented nine crystal structures of Mpro bound to a series of perampanel analogs, providing detailed structural insights into their mechanism of action and structure-activity relationship. These insights reveal strategies for rational inhibitor design efforts in the context of active-site flexibility and potential resistance mechanisms.