Article
Chemistry, Medicinal
Dan Wei, Hanlin Wang, Qinghe Zeng, Wenjing Wang, Bingbing Hao, Xule Feng, Peipei Wang, Ning Song, Weijuan Kan, Guifang Huang, Xiaoyu Zhou, Minjia Tan, Yubo Zhou, Ruimin Huang, Jia Li, Xiao-Hua Chen
Summary: TNBC is highly aggressive and clinically challenging due to limited treatment options. Targeting transcription-associated CDK9 with a novel degrader compound shows great promise in inhibiting TNBC cell growth and inducing apoptosis by downregulating transcriptional targets like MYC. This study establishes compound 45 as a potent and efficacious CDK9 degrader for potential targeted therapy in TNBC.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
H. P. Eikesdal, S. Yndestad, A. Elzawahry, A. Llop-Guevara, B. Gilje, E. S. Blix, H. Espelid, S. Lundgren, J. Geisler, G. Vagstad, A. Venizelos, L. Minsaas, B. Leirvaag, E. G. Gudlaugsson, O. K. Vintermyr, H. S. Aase, T. Aas, J. Balmana, V Serra, E. A. M. Janssen, S. Knappskog, P. E. Lonning
Summary: In primary treatment-naive triple negative breast cancer patients, olaparib showed a high clinical response rate in patients with homologous recombination deficiency, surpassing those without this defect. This demonstrates the effectiveness of olaparib in this population.
ANNALS OF ONCOLOGY
(2021)
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)
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.
Review
Biochemistry & Molecular Biology
Halima Alsamri, Yusra Al Dhaheri, Rabah Iratni
Summary: Triple-negative breast cancer (TNBC) lacks the expression of hormone receptors and is highly aggressive and lethal. Conventional therapies and chemotherapeutic agents have limited effectiveness against TNBC. Phytochemicals, such as carnosol, have shown efficacy against TNBC by targeting key pathways involved in cancer development and progression. This review discusses the molecular mechanisms of carnosol in inhibiting TNBC and identifies it as a potential novel targeting protein degradation molecule.
Review
Oncology
Filippo Borri, Annarita Granaglia
Summary: This review discusses the pathological aspects, molecular markers, and new frontier of immunotherapy in triple-negative breast cancer (TNBC), emphasizing the importance of histological diagnosis on clinical outcomes.
SEMINARS IN CANCER BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Wanfu Wu, Margaret Warner, Li Wang, Wei-Wei He, Ruipeng Zhao, Xiaoxiang Guan, Cindy Botero, Bo Huang, Charlotte Ion, Charles Coombes, Jan-Ake Gustafsson
Summary: Comparing gene expression profiles of malignant parts and normal adjacent parts of TNBC breasts revealed that CYP-mediated pathways may drive TNBC. However, despite being expressed in TNBC, ER13 is unlikely to be a tumor suppressor as its absence of main tethering partners renders it ineffective on genes related to proliferation and inflammation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, General & Internal
A. Bardia, S. A. Hurvitz, S. M. Tolaney, D. Loirat, K. Punie, M. Oliveira, A. Brufsky, S. D. Sardesai, K. Kalinsky, A. B. Zelnak, R. Weaver, T. Traina, F. Dalenc, P. Aftimos, F. Lynce, S. Diab, J. Cortes, J. O'Shaughnessy, V Dieras, C. Ferrario, P. Schmid, L. A. Carey, L. Gianni, M. J. Piccart, S. Loibl, D. M. Goldenberg, Q. Hong, M. S. Olivo, L. M. Itri, H. S. Rugo
Summary: Patients with metastatic triple-negative breast cancer treated with Sacituzumab govitecan had significantly longer progression-free and overall survival compared to standard chemotherapy, but experienced more frequent myelosuppression and diarrhea as adverse events.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Yan Ma, Haibo Zhang, Cheng Chen, Lixin Liu, Ting Ding, Ying Wang, Dachang Ma, Xiaoling Ling, Xiaohua Chen, Jianping Li, Guansheng Zhong, Guoqing Ru, Lei Zhang, Jianming Tang
Summary: This study reveals that TRIM32 is upregulated and negatively associated with survival of TNBC patients. Radiotherapy enhances the expression of TRIM32, while depletion of TRIM32 reduces TNBC radioresistance. Mechanistically, radiotherapy promotes the association between TRIM32 and nuclear STAT3, which suppresses TC45-induced dephosphorylation of STAT3, resulting in increased STAT3 transcriptional activation and TNBC radioresistance. TRIM32 and STAT3 phosphorylation are co-expressed in TNBC tissues and correlated with poor prognosis of TNBC patients.
Review
Biochemistry & Molecular Biology
Xiao-Li Zhou, Fang Zhao, Yong-Tao Xu, Yuan-Yuan Guan, Tong Yu, Yi-Zhe Zhang, Ying-Chao Duan, Yuan Zhao
Summary: Targeted protein degradation using proteolysis-targeting chimeras (PROTACs) is an effective strategy for drug discovery, especially in cancer therapy. BET proteins, as therapeutic targets in cancer treatment, have been extensively studied and there have been recent advances in BET-targeting PROTACs.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
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
Chemistry, Medicinal
Mariya Yordanova, Audrey Hubert, Saima Hassan
Summary: PARPi treatment in TNBC patients shows great potential beyond BRCA(MUT) status, potentially effective for various patient subgroups. Treatment outcomes are influenced by factors such as BRCA(MUT) status, number of chemotherapy lines, requiring careful dosing adjustments and patient subgroup selection.
Article
Biochemistry & Molecular Biology
Jinyun Chen, Yujie Yang, Wade A. Russu, William K. Chan
Summary: The study reports that AHR undergoes chaperone-mediated autophagy in MDA-MB-468 triple-negative breast cancer cells, with specific characteristics and regulatory mechanisms involved in the degradation process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, Research & Experimental
Eun Choi, Gil-im Mun, Joohyun Lee, Hanhee Lee, Jaeho Cho, Yun-Sil Lee
Summary: Mutations in the BRCA1 gene increase the risk of developing breast cancer, but only a minority of patients carry these mutations. A recent study suggests that reduced BRCA1 levels, rather than mutations, are responsible for almost half of all triple-negative breast cancer (TNBC) cases. Understanding the function and regulation of BRCA1 can help improve treatment strategies for BRCA1-related breast cancer patients, especially those with TNBC.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
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)