Review
Cell Biology
Jonathan Wooten, Nicole Mavingire, Katherine Damar, Andrea L. Perez, Eileen Brantley
Summary: Poly(ADP-ribose) polymerase 1 (PARP1) is involved in DNA repair mechanisms, and PARP inhibitors (PARPi) show synthetic lethality in malignancies with a deficiency in the homologous recombination (HR) pathway. Triple-negative breast cancer (TNBC) patients with HR mediator mutations, such as BRCA1 and BRCA2, can respond to PARPi. However, PARPi resistance is a common issue. This review discusses the roles of PARP in DNA repair, mechanisms of PARPi resistance in TNBC, and recent advances in overcoming PARPi resistance in TNBC.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Review
Oncology
Ying Li, Zhijun Zhan, Xuemin Yin, Shujun Fu, Xiyun Deng
Summary: TNBC, characterized by absence of ER, PR, and HER2 expression, is a highly aggressive subtype of breast cancer. Conventional chemotherapy remains the main treatment, but the lack of targeted therapies has led to exploration of PARP inhibitors and immune checkpoint inhibitors as potential options. Other agents targeting various pathways are also under investigation.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Maroun Bou Zerdan, Tala Ghorayeb, Fares Saliba, Sabine Allam, Morgan Bou Zerdan, Marita Yaghi, Nadeem Bilani, Rola Jaafar, Zeina Nahleh
Summary: Triple negative breast cancer (TNBC) is a subtype of breast cancer with limited effectiveness of chemotherapy. In recent years, new biologic and targeted therapies have emerged for the treatment of TNBC. This review assesses the latest developments in the basic characterization, subtyping, and treatment of TNBC, including the development of novel drugs.
Review
Biochemistry & Molecular Biology
Mateusz Kciuk, Adrianna Gielecinska, Somdutt Mujwar, Mariusz Mojzych, Renata Kontek
Summary: Synthetic lethal interactions involving CDKs with MYC, PARP-1, and TP53 are emerging as potential targets for selectively targeting tumor cells with DNA repair defects. These interactions reveal the crucial roles of cell cycle regulatory proteins in the DNA damage response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Prarthana Chatterjee, Rohit Karn, Arnold Emerson Isaac, Smita Ray
Summary: Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors. This makes TNBC insensitive to traditional endocrine therapies. Current treatment options are limited to chemotherapy and radiation therapy, which often have side effects and lead to poor outcomes. Synthetic lethality, a promising approach that targets undruggable genes, such as oncogenes or tumor suppressor genes, could offer new treatment opportunities for TNBC. This review explores the mechanisms of synthetic lethal interactions in TNBC, the role of PARP inhibitors in inducing these interactions, and the limitations faced by synthetic lethal interactors, with a focus on personalized medicine for TNBC patients.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2023)
Article
Oncology
Ganesh Pai Bellare, Bhaskar Saha, Birija Sankar Patro
Summary: Autophagy contributes to de novo resistance to PARP inhibitor, talazoparib. Inhibiting autophagy can enhance the therapeutic efficacy of talazoparib in BRCA1-WT breast cancer cells, leading to cell death.
BRITISH JOURNAL OF CANCER
(2021)
Article
Oncology
Xiao-Feng Xie, Nan-Qiang Wu, Jin-Feng Wu, Guang-Lin Zhang, Jin-Feng Guo, Xue-Lian Chen, Cai-Wen Du
Summary: The combination of PARP inhibitor and CXCR4 inhibitor shows enhanced anti-tumor effect in BRCA-proficient triple-negative breast cancer, potentially broadening the indication of PARP inhibitors for this patient population.
Article
Biochemistry & Molecular Biology
Gamze Guney Eskiler, Sevinc Yanar, Gurler Akpinar, Murat Kasap
Summary: Proteomic analysis revealed 10 differentially regulated proteins in TAL-resistant TNBC cells, with predicted changes in EGF/FGF signaling pathways and the AMPK signaling pathway, as well as altered phosphorylation/dephosphorylation dynamics in TAL-resistant cells. These findings suggest potential targets to overcome TAL resistance in TNBC treatment.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2021)
Article
Oncology
Jennifer K. Litton, J. Thaddeus Beck, Jason M. Jones, Jay Andersen, Joanne L. Blum, Lida A. Mina, Raymond Brig, Michael Danso, Yuan Yuan, Antonello Abbattista, Kay Noonan, Alexander Niyazov, Jayeta Chakrabarti, Akos Czibere, William F. Symmans, Melinda L. Telli
Summary: This study evaluates the efficacy and safety of neoadjuvant talazoparib in patients with germline BRCA1/2-mutated early-stage TNBC. The results show that talazoparib monotherapy is active in these patients, although the pCR rates did not meet the prespecified threshold. Talazoparib was generally well tolerated.
Review
Medicine, Research & Experimental
Tian Tian, Yangzhi Zhao, Jingying Zheng, Shunzi Jin, Zhongshan Liu, Tiejun Wang
Summary: TNBC, the most malignant subtype of breast cancer, is characterized by high rates of cell proliferation and poor prognosis. Chemotherapy is the primary therapeutic strategy, but targeted therapies for TNBC are lacking. CircRNAs show potential as biomarkers for TNBC diagnosis, prognosis, and treatment, but further research is needed to understand their functions.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Review
Oncology
Mashael Algethami, Sanat Kulkarni, Maaz T. Sadiq, Hiu K. C. Tang, Juliette Brownlie, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
Summary: Despite the poor overall outcomes for patients with advanced ovarian cancer, a precision medicine strategy focusing on DNA repair, such as PARP inhibitors, has shown promising results in improving survival. Additionally, antiangiogenic agents, intraperitoneal chemotherapy, and immunotherapeutic approaches could also positively impact patient outcomes.
CANCER MANAGEMENT AND RESEARCH
(2022)
Article
Oncology
Yves Pommier, Anish Thomas
Summary: ADCs are effective in delivering cytotoxic agents to tumors, and two ADCs delivering TOP1 poisons have been FDA-approved. A recent study introduced a TOP1-anti B7-H4 ADC that showed synergistic effect with a PARP1-selective inhibitor.
CLINICAL CANCER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Palmiro Poltronieri, Masanao Miwa, Mitsuko Masutani
Summary: ADP-ribosylation plays a crucial role in post-translational modifications of proteins, involving functions such as DNA repair, transcription, and cell signaling. Enzymes involved in monoADP-ribosylation/polyADP-ribosylation (MAR/PAR) cycling also play important roles in cancers, with potential applications in non-oncological diseases. The field is still actively uncovering novel enzymes at a rapid pace.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Xiao-Fei Chang, Xiao-Lu Ren, Jie-Quan Yang, Jian-Jun Shi, Jun-Heng Bai, Meng-Sheng Cui, Wen-Wen Dong
Summary: The study found that PARPi had better progression-free survival and overall response rate compared to chemotherapy in breast cancer patients, but also had a higher risk of grade 3-4 thrombocytopenia. PARPi was a better choice for patients who had not received previous platinum treatment.
Article
Biochemistry & Molecular Biology
Sridhar Priyankha, Varatharaj Rajapandian, Kandhan Palanisamy, S. M. Esther Rubavathy, Ramasamy Thilagavathi, Chelliah Selvam, Muthuramalingam Prakash
Summary: Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous disease caused by missing certain receptors. In this study, researchers screened natural products and identified six hit compounds with strong binding affinity towards the protein PARP-1, which is involved in the development of TNBC. Molecular dynamics simulations and calculations showed that two of these compounds had stronger binding energies with PARP-1 than an FDA-approved PARPi. The study offers valuable insights for the potential use of PARPi in TNBC treatment, and the findings were validated through comparison with an FDA-approved PARPi.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Correction
Biochemistry & Molecular Biology
Mohamed Marzouk, Shimaa M. Khalifa, Amal H. Ahmed, Ahmed M. Metwaly, Hala Sh. Mohammed, Hanan A. A. Taie
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Gerardo Andres Libreros-Zuniga, Danilo Pava e Pavao, Vinicius de Morais Barroso, Nathalya Cristina de Moraes Roso Mesquita, Saulo Fehelberg Pinto Braga, Glaucius Oliva, Rafaela Salgado Ferreira, Kelly Ishida, Marcio Vinicius Bertacine Dias
Summary: Tuberculosis is a major global cause of death, and the emergence of drug-resistant strains has increased the burden of this disease. New alternative therapies are constantly needed, and recent research has identified small molecules as potential inhibitors of Ldts in M. tuberculosis, which have antimycobacterial activity.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Xiao-Dong Wang, Yong-Si Liu, Ming-Hao Hu
Summary: In this study, a selffolded fluorescent probe was designed to selectively illuminate G4s by unfolding its intramolecular aggregation mediated by G4 binding. This probe showed more controllable background emission and promising ability to track G4 forming dynamics compared to previous disaggregation-induced emission (DIE) probes.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yu Xiang, Zhuo Yuan, Qichuan Deng, Linshen Xie, Dongke Yu, Jianyou Shi
Summary: This review provides a brief description of the diagnosis, pathogenesis, and potential therapeutic inhibitors for renal fibrosis. Currently, there are no clear therapeutic targets or drugs for renal fibrosis; however, some natural products may have potential efficacy for treating renal fibrosis.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Simone Giovannuzzi, Anna Nikitjuka, Bruna Rafaela Pereira Resende, Michael Smietana, Alessio Nocentini, Claudiu T. Supuran, Jean-Yves Winum
Summary: Boron-based compounds have been extensively studied in medicinal chemistry, playing a crucial role in designing small molecule drugs for various diseases. Boron is particularly valuable in developing inhibitors for metalloenzymes carbonic anhydrases, and it can modulate ligand recognition ability and selectivity. Recent advancements have led to the discovery of novel boron-based inhibitors that can inhibit carbonic anhydrases through a Lewis acid-base mechanism. Further research is needed to fully explore the potential of boron-based inhibitors and advance their clinical applications.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Xinxin Liu, Lei Chen, Ze Chen
Summary: This study developed a nanostructured photosensitizer loaded with oxygen-throttling drug and demonstrated its enhanced cytotoxicity against tumor cells under hypoxic conditions. Animal experiments showed the enhanced tumor targeting capability of the photosensitizer and its inhibitory effect on tumor growth.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Shuai Jiang, Wen-Yan Li, Zai-Feng Yuan, Qin-Shi Zhao
Summary: This study isolated two new dimeric Lycopodium alkaloids and twelve previously undescribed Lycopodium alkaloids from Lycopodiastrum casuarinoides. The structures of these compounds were determined and their inhibitory activities on the Cav3.1 channel were evaluated.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yan Yang, Dong-Xiao Yan, Rui-Xue Rong, Bing-Ye Shi, Man Zhang, Jing Liu, Jie Xin, Tao Xu, Wen-Jie Ma, Xiao-Liu Li, Ke-Rang Wang
Summary: In this study, a series of nucleolar fluorescent probes based on naphthalimide derivatives were designed and synthesized, which could achieve clear nucleolar staining in living cells. The results showed that these probes exhibited good targeting to the cell nucleolus and could bind to RNA and enhance fluorescence. This has positive implications for the diagnosis and treatment of nucleolus-related diseases.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yongxi Dong, Fang Wang, Jinlan Wen, Yongqing Mao, Shanhui Zhang, Tiemei Long, Zhangxiang Yang, Lei Li, Jiquan Zhang, Li Dong, Gang Liu, Jianwei Xu
Summary: The hybrid molecules of Scutellarein and Tertramethylpyrazine show excellent neuroprotective and antiplatelet effects in the treatment of ischemic stroke. Compound 1e is particularly effective, enhancing cell membrane permeability and inhibiting cell uptake, as well as significantly reducing cerebral infarction volume.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yu Chen, Yuanyuan Ying, Jonathan Lalsiamthara, Yuheng Zhao, Saber Imani, Xin Li, Sijing Liu, Qingjing Wang
Summary: This paper examines the role and metabolic regulation of NAD+ in bacteria, highlighting its impact on physiology and virulence. It explores enzymes associated with NAD+ metabolism as potential targets for antibacterial drugs and vaccine candidates. Additionally, it scrutinizes the medical potential of NAD+ and provides insights for its application in biomedicine.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Jon Macicior, Daniel Fernandez, Silvia Ortega-Gutierrez
Summary: Hutchinson-Gilford progeria syndrome (HGPS), also known as progeria, is a rare genetic disease that causes premature aging and significantly reduces life expectancy. Currently, there is only one approved drug for treating progeria, but its efficacy is limited. Progerin levels are believed to be the most important biomarker related to disease severity.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Fuko Hirano, Naoya Kondo, Yusuke Murata, Aya Sudani, Takashi Temma
Summary: Fluorinated alpha-methyl 3BPA derivatives showed improved water solubility, tumor targetability, and biodistribution compared to 3BPA and BPA, resulting in significantly improved tumor-to-normal tissue ratios.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Ying Shi, Jiaqin Tang, Shumeng Zhi, Ruiqi Jiang, Qing Huang, Lei Sun, Zhizhong Wang, Yanran Wu
Summary: Necroptosis is a type of cell death associated with various diseases. In this study, we identified a small molecule inhibitor, SY-1, that effectively blocks necroptosis by inhibiting the phosphorylation of RIP1/RIP3/MLKL pathway. SY-1 also showed protective effects against TNF-induced hypothermia and improved survival in mice with SIRS. These findings highlight the potential therapeutic applications of SY-1.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Andrea Bagan, Sonia Abas, Judith Pala-Pujadas, Alba Irisarri, Christian Grinan-Ferre, Merce Pallas, Itziar Muneta-Arrate, Carolina Muguruza, Luis F. Callado, Belen Perez, Elies Molins, Jose A. Morales-Garcia, Carmen Escolano
Summary: Recent studies have identified the modulation of imidazoline I-2 receptors (I-2-IR) by selective ligands as a potential strategy for treating neurodegenerative diseases. This study reports a family of bicyclic alpha-iminophosphonates that show high affinity and selectivity for I-2-IR and demonstrates their neuroprotective and anti-inflammatory effects in in vitro and in vivo models. The findings emphasize the importance of exploring structurally novel I-2-IR ligands for therapeutic strategies in neurodegeneration.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Qiuping Xiang, Tianbang Wu, Cheng Zhang, Chao Wang, Hongrui Xu, Qingqing Hu, Jiankang Hu, Guolong Luo, Xiaoxi Zhuang, Xishan Wu, Yan Zhang, Yong Xu
Summary: This study reports the discovery of a 1-(indolizin-3-yl)ethan-1-one derivative as a potent and selective CBP bromodomain inhibitor for AML drug development.
BIOORGANIC CHEMISTRY
(2024)