Article
Oncology
Jose P. Leone, Noah Graham, Julieta Leone, Sara M. Tolaney, Bernardo A. Leone, Rachel A. Freedman, Michael J. Hassett, Carlos T. Vallejo, Eric P. Winer, Nancy U. Lin, Nabihah Tayob
Summary: This study developed a tool called "ESTIMATE-TN" to assess the risk of breast cancer-specific mortality (BCSM), non-BCSM, and all-cause mortality in non-metastatic triple-negative breast cancer (TNBC) patients. The tool allows input of patient and tumor characteristics and provides a nonparametric estimate of cumulative risks using Gray's subdistribution method.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Oncology
Xia Qiu, Tianjiao Zhao, Ran Luo, Ran Qiu, Zhaoming Li
Summary: TNBC is a subtype of breast cancer that lacks ER, PR, and HER-2 receptors. TAMs are macrophages infiltrating the tumor, derived from circulating blood mononuclear cells, and play a role in the occurrence and metastasis of TNBC, possibly serving as potential biomarkers for prognosis prediction.
FRONTIERS IN ONCOLOGY
(2022)
Review
Cell Biology
Wenwen Zhang, Xiaoxiang Guan, Jinhai Tang
Summary: Triple-negative breast cancer (TNBC) is known for its aggressive behavior and poor prognosis. Recent studies have identified various long non-coding RNAs (lncRNAs) that play important roles in TNBC tumorigenesis. Potential therapeutic strategies using lncRNAs are being explored in clinical settings for TNBC patients.
CELL PROLIFERATION
(2021)
Review
Oncology
Masa Brumec, Monika Sobocan, Iztok Takac, Darja Arko
Summary: Triple-negative breast cancer lacks hormone receptors and HER2 amplifications, posing challenges in treatment selection. However, some TNBCs express androgen receptor (AR) which can be a therapeutic target. This review summarizes clinical features and potential therapies for AR-positive TNBC and highlights the need for further research on AR signaling pathways.
Letter
Medicine, General & Internal
Ryan Sun, Lee-Jen Wei
Summary: This article discusses the clinical benefits of pembrolizumab combined with chemotherapy in patients with triple-negative breast cancer. The authors suggest that both hazard values and ratios should be considered when evaluating clinical benefits.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Cell Biology
Hong Luo, Zhicheng Zhou, Shan Huang, Mengru Ma, Manyu Zhao, Lixu Tang, Yuan Quan, Yiming Zeng, Li Su, Jongchan Kim, Peijing Zhang
Summary: The cell cycle-related E3 ubiquitin ligase, CHFR, serves as a key negative regulator of ZEB1 in TNBC, enhancing the therapeutic potential against TNBC cells by modulating ZEB1.
CELL DEATH & DISEASE
(2021)
Review
Pharmacology & Pharmacy
Asad Mustafa Karim, Jeong Eun Kwon, Tanveer Ali, Jinsoo Jang, Irfan Ullah, Yeong-Geun Lee, Dae Won Park, Juha Park, Jin Woo Jeang, Se Chan Kang
Summary: TNBC is a subtype of breast cancer with poor prognosis and aggressive behavior, accounting for 10-15% of new cases. The unique mutational profile of somatic and germline modifications in TNBC is different from other subtypes. Understanding the genomic modifications in TNBC is essential for developing treatment strategies.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Oncology
Rama Rao Malla, Padmaraju Vasudevaraju, Rahul Kumar Vempati, Marni Rakshmitha, Neha Merchant, Ganji Purnachandra Nagaraju
Summary: Triple-negative breast cancer (TNBC) is an aggressive and immunogenic subtype of breast cancer. T-regulatory cell (Treg) infiltration and other mechanisms contribute to drug resistance and early recurrence. Understanding the role of tumor-infiltrating Tregs in tumor progression and metabolic reprogramming is crucial for developing immune-based therapeutics.
Article
Oncology
Laura M. Spring, Erika Nakajima, Jennifer Hutchinson, Elene Viscosi, Gayle Blouin, Colin Weekes, Hope Rugo, Beverly Moy, Aditya Bardia
Summary: Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan has shown promising therapeutic activity and received accelerated approval for the treatment of these patients. Limited information is available regarding adverse event management with this agent.
Article
Cell Biology
Chen Li, Xiaolong Wang, Tong Chen, Wenhao Li, Xianyong Zhou, Lishui Wang, Qifeng Yang
Summary: This study found that Huaier, a traditional Chinese medicine, could induce immunogenic cell death in triple-negative breast cancer cells. The results showed that Huaier-treated breast cancer cells enhanced the maturation of dendritic cells and inhibited tumor growth. Further studies revealed that circCLASP1 was involved in the Huaier-induced immunogenicity. These findings have significant translational potential in the clinical treatment of triple-negative breast cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Yong-Han Su, Yi-Zhen Wu, David K. K. Ann, Jenny Ling-Yu Chen, Ching-Ying Kuo
Summary: Obesity is a risk factor for various cancers, including breast cancer. Adipose tissue disturbance in obesity is closely related to cancer progression and resistance to standard treatments. In this study, diet-induced obesity promoted tumor growth and reduced tumor response to radiotherapy in the mouse model of triple-negative breast cancer. Serpine1 was found to be elevated in the blood of obese mice and enriched in the tumor microenvironment.
CELL DEATH & DISEASE
(2023)
Review
Oncology
Mark van Barele, Bernadette A. M. Heemskerk-Gerritsen, Yvonne V. Louwers, Mijntje B. Vastbinder, John W. M. Martens, Maartje J. Hooning, Agnes Jager
Summary: Triple-negative breast cancers are more common in younger women and do not express ER or PR, making them considered hormone-insensitive. Treatment usually involves chemotherapy, which can lead to premature ovarian insufficiency and impact quality of life. Hormone replacement therapy is contraindicated for TNBC patients due to inconclusive data on safety and possible increased risk of recurrence.
Letter
Medicine, General & Internal
Shuvadeep Ganguly, Ajay Gogia
Summary: In the KEYNOTE-522 trial, the addition of Pembrolizumab to neoadjuvant chemotherapy improved pathological complete response rate in early triple-negative breast cancer patients and also improved event-free survival. However, this improvement was predominantly observed in patients who did not achieve a pathological complete response.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Yifeng Cao, Chuyang Chen, Yi Tao, Weifeng Lin, Ping Wang
Summary: Triple-negative breast cancer (TNBC) is characterized by extensive tumor heterogeneity at both the pathologic and molecular levels, leading to increased mortality of patients due to accelerated aggressiveness and terrible metastasis. Hindered by the negative expression of certain receptors, targeted therapy has been challenging, but the higher immune response in TNBC compared to other breast cancer types makes it suitable for immunotherapy.
Article
Biochemistry & Molecular Biology
Milica Vulin, Charly Jehanno, Atul Sethi, Ana Luisa Correia, Milan M. S. Obradovic, Joana Pinto Couto, Marie-May Coissieux, Maren Diepenbruck, Bogdan-Tiberius Preca, Katrin Volkmann, Priska Auf Der Maur, Alexander Schmidt, Simone Munst, Loic Sauteur, Michal Kloc, Marta Palafox, Adrian Britschgi, Vincent Unterreiner, Olaf Galuba, Isabelle Claerr, Sandra Lopez-Romero, Giorgio G. Galli, Daniel Baeschlin, Ryoko Okamoto, Savas D. Soysal, Robert Mechera, Walter P. Weber, Thomas Radimerski, Mohamed Bentires-Alj
Summary: Plasticity is a defining characteristic of cancer subtypes, with triple-negative breast cancer (TNBC) displaying high cellular plasticity and worsened prognosis. In this study, the authors identified three polo-like kinase 1 (PLK1) inhibitors that induce expression and activity of estrogen receptor alpha (ER alpha), leading to a differentiation program characterized by DNA damage, mitotic arrest, and cell death in TNBC cells. Surviving cells after PLK1 inhibition showed decreased tumorigenic potential, and targeting PLK1 reduced tumor growth in both cell line and patient-derived xenograft models. Furthermore, the upregulated genes upon PLK1 inhibition were associated with better overall survival in breast cancer patients. These findings suggest that differentiation therapy based on PLK1 inhibition may be a potential alternative strategy to treat TNBC.
Article
Biochemistry & Molecular Biology
Baojuan Han, Jian Huang, Yunfeng Han, Jie Hao, Xueya Wu, Hongtao Song, Xuesong Chen, Qiang Shen, Xiaoqun Dong, Hui Pang, Li Cai
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2019)
Article
Oncology
Hengqiang Zhao, Shihong Wu, Hehe Li, Qingke Duan, Zhengle Zhang, Qiang Shen, Chunyou Wang, Tao Yin
MOLECULAR THERAPY-ONCOLYTICS
(2019)
Article
Cell Biology
Lu Lu, Hang Li, Xin Wu, Jun Rao, Jia Zhou, Saijun Fan, Qiang Shen
CELL PROLIFERATION
(2020)
Article
Chemistry, Medicinal
Zhiqing Liu, Haiying Chen, Pingyuan Wang, Yi Li, Eric A. Wold, Paul G. Leonard, Sarah Joseph, Allan R. Brasier, Bing Tian, Jia Zhou
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Eric A. Wold, Erik J. Garcia, Christopher T. Wild, Joanna M. Miszkiel, Claudia A. Soto, Jianping Chen, Konrad Pazdrak, Robert G. Fox, Noelle C. Anastasio, Kathryn A. Cunningham, Jia Zhou
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Jimin Xu, Judith Berastegui-Cabrera, Marta Carretero-Ledesma, Haiying Chen, Yu Xue, Eric A. Wold, Jeronimo Pachon, Jia Zhou, Javier Sanchez-Cespedes
Summary: Compound 16 (JMX0493) is reported as a potent inhibitor of HAdV infection, displaying submicromolar IC50 values, a higher selectivity index (SI > 100), and a 2.5-fold virus yield reduction compared to the hit compound niclosamide. Mechanistic studies suggest that compound 16 achieves its antiviral activity against HAdV through inhibition of viral particle escape from the endosome, blocking subsequent uncoating and presentation of lytic protein VI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Zhiqing Liu, Pingyuan Wang, Eric A. Wold, Qiaoling Song, Chenyang Zhao, Changyun Wang, Jia Zhou
Summary: Researchers have made significant progress in the discovery and development of small-molecule inhibitors targeting the canonical WNT pathway in recent years, with a focus on specific target proteins and candidates in clinical trials. The study also highlights the challenges and opportunities in effectively targeting this pathway while maintaining a balance between efficacy and toxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Zu Ye, Shengfeng Xu, Yin Shi, Albino Bacolla, Aleem Syed, Davide Moiani, Chi-Lin Tsai, Qiang Shen, Guang Peng, Paul G. Leonard, Darin E. Jones, Bin Wang, John A. Tainer, Zamal Ahmed
Summary: In this study, GRB2 was found to play a crucial role in DNA double-strand break repair by forming a complex with MRE11 to promote efficient homology-directed repair initiation and releasing MRE11 through ubiquitination. Depletion of RBBP6 leads to prolonged HDR defects, highlighting GRB2's importance in the repair process.
Article
Chemistry, Medicinal
Zhiqing Liu, Yi Li, Haiying Chen, Hsien-Tsung Lai, Pingyuan Wang, Shwu-Yuan Wu, Eric A. Wold, Paul G. Leonard, Sarah Joseph, Haitao Hu, Cheng-Ming Chiang, Allan R. Brasier, Bing Tian, Jia Zhou
Summary: A potent BRD4 BD1-selective inhibitor ZL0590 has been discovered, targeting a unique binding site and exhibiting significant anti-inflammatory activities. This finding provides new insights into the complex biology of bromodomain specificity among BRD4 and its protein-protein interaction partners.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Xi Liu, Jimin Xu, Jia Zhou, Qiang Shen
Summary: Cancer is a major global health issue, with chemotherapy being the primary treatment option. Oridonin and its derivatives have shown promise in overcoming therapeutic resistance in cancer treatment, with potential as clinical trial drug candidates.
Article
Chemistry, Medicinal
Na Ye, Wangzhi Qin, Sheng Tian, Qingfeng Xu, Eric A. Wold, Jia Zhou, Xue-Chu Zhen
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Oncology
Lihua Yang, Hongbo Zhao, Xueqin Yin, Hong Liang, Zhi Zheng, Qiang Shen, Wanqin Hu
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
(2020)
Article
Oncology
Yutian Miao, Qiang Shen, Siheng Zhang, Hehai Huang, Xiaojing Meng, Xianchong Zheng, Zhuocheng Yao, Zhanxin He, Sitong Lu, Chunqing Cai, Fei Zou
BREAST CANCER RESEARCH
(2019)
Meeting Abstract
Oncology
J. Dong, J. Xu, H. Kim, J. Zhou, Q. Shen
Article
Oncology
Zhaoqing Li, Tingting Zhu, Yini Xu, Chuanqiang Wu, Jinliang Chen, Yu Ren, Lingping Kong, Shanshan Sun, Wenyu Guo, Yu Wang, Chao Jing, Jabin Dong, Jia Zhou, Lun Zhang, Qiang Shen, Xuan Zhou
AMERICAN JOURNAL OF CANCER RESEARCH
(2019)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
