Article
Biochemistry & Molecular Biology
Aman Chandra Kaushik, Zhongming Zhao
Summary: Breast cancer is highly heterogeneous and personalized treatment has become a new strategy. Triple-negative breast cancer (TNBC) is a subtype with diverse genetic markers. Six effective drugs against TNBC cell lines were identified through database scanning.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
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
Multidisciplinary Sciences
Bhavana Palakurthi, Shaneann R. Fross, Ian H. Guldner, Emilija Aleksandrovic, Xiyu Liu, Anna K. Martino, Qingfei Wang, Ryan A. Neff, Samantha M. Golomb, Cheryl Lewis, Yan Peng, Erin N. Howe, Siyuan Zhang
Summary: Chemotherapy priming enhances the response to immune checkpoint blockade in triple-negative breast cancers, but immune suppressive myeloid cells may hinder its efficacy. Through single-cell analysis, the authors characterize these immune suppressive myeloid cells and identify STAT1 signaling as a regulator of their suppressive state.
NATURE COMMUNICATIONS
(2023)
Review
Materials Science, Multidisciplinary
Xiangyi Kong, Yihang Qi, Xiangyu Wang, Rui Jiang, Jing Wang, Yi Fang, Jidong Gao, Kuo Chu Hwang
Summary: The therapeutic effect of highly malignant triple negative breast cancer (TNBC) is negatively affected by resistant clone formation and severe toxicity. Nano delivery system effectively suppresses and kills tumor cells by targeted delivery of chemotherapeutic drugs, gene fragments, and immune enhancing factors. Combined with photothermal ablation therapy, it achieves synergism, toxicity reduction, gene inhibition, and immune system activation. These nanoparticle delivery systems revolutionize drug design and usage, reducing adverse effects of toxic chemodrugs.
PROGRESS IN MATERIALS SCIENCE
(2023)
Review
Nanoscience & Nanotechnology
Siyan Liu, Jing Li, Lin Gu, Kunzhe Wu, Hua Xing
Summary: Chemoimmunotherapy shows promise for treating TNBC, but challenges remain in improving efficacy and reducing side effects.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Yang Liu, Yueting Hu, Jinqi Xue, Jingying Li, Jiang Yi, Jiawen Bu, Zhenyong Zhang, Peng Qiu, Xi Gu
Summary: Immunotherapy has emerged as a promising strategy for treating triple-negative breast cancer (TNBC), which stimulates the immune system to kill tumor cells and offers new hope for patients. Breakthroughs in immune checkpoint inhibitors (ICIs) have led to individualized immunotherapy schedules and the combination with other treatment methods to overcome drug resistance.
Review
Oncology
Kai Hou, Zeng Ning, Hongbo Chen, Yiping Wu
Summary: This review discusses the mechanisms and prospects of nanotechnology in the treatment of TNBC, providing potential new strategies for the diagnosis and treatment of TNBC.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Marine Lemesle, Marine Geoffroy, Fabien Alpy, Catherine-Laure Tomasetto, Sandra Kuntz, Isabelle Grillier-Vuissoz
Summary: This study investigated the role of CLDN1 in triple-negative breast cancer (TNBC) and found that CLDN1 can increase the sensitivity of TNBC cells to chemotherapy drugs. The findings support the use of CLDN1 as a predictive marker for chemotherapy response in TNBC.
Article
Biochemistry & Molecular Biology
Paul R. Hollis, Robert J. Mobley, Jyoti Bhuju, Amy N. Abell, Carrie Hayes Sutter, Thomas R. Sutter
Summary: Cytochrome P4501B1 (CYP1B1) is elevated in breast cancer and associated with aggressive cancer phenotypes. Knockdown of CYP1B1 in triple-negative breast cancer cell lines resulted in decreased invasive characteristics and increased chemosensitivity. Clinical analysis showed that high CYP1B1 expression was associated with lower overall and disease-free survival in breast cancer patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Bingye Shi, Wei Zhang, Tao Wang, Zhenyu Cui
Summary: This study identified key genes related to TNBC development and observed their potential impact on tumor immune microenvironment and patient survival. These key genes interact mutually and can be influenced by common BC-related mutations. Additionally, a 11-gene risk model was established with a robust performance in predicting 5-15-year survival, and some new drugs were proposed potentially effective in TNBC based on the CRG strategy.
BMC BIOINFORMATICS
(2023)
Article
Oncology
Silvia Filippi, Elena Paccosi, Alessio Balzerano, Margherita Ferretti, Giulia Poli, Juri Taborri, Stefano Brancorsini, Luca Proietti-De-Santis
Summary: The increased expression of Cockayne Syndrome group A (CSA) protein in breast cancer cells provides a potential target for effective anti-cancer therapies. The suppression of CSA by ASOs has shown promising results in reducing tumorigenicity and increasing sensitivity to chemotherapy in breast cancer cells.
Article
Immunology
Chundi Gao, Huayao Li, Cun Liu, Xiaowei Xu, Jing Zhuang, Chao Zhou, Lijuan Liu, Fubin Feng, Changgang Sun
Summary: In this study, it was found that TNBC patients in the high TMB group had a higher survival rate, with differences in immune cell infiltration between the two groups. The FAT3 gene plays an important role in TNBC, not only related to patient prognosis, but also affecting immune cell infiltration.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu
Summary: This study aims to determine the mechanisms of action of the histone deacetylase inhibitor panobinostat in TNBC and provide a rationale for effective drug combinations against this aggressive disease.
NPJ PRECISION ONCOLOGY
(2023)
Article
Cell Biology
Gaoming Liao, Yiran Yang, Aimin Xie, Zedong Jiang, Jianlong Liao, Min Yan, Yao Zhou, Jiali Zhu, Jing Hu, Yunpeng Zhang, Yun Xiao, Xia Li
Summary: This study established a drug sensitivity prediction model based on homologous recombination deficiency (HRD) and explored the effect and mechanisms of HRD status on the efficacy of anticancer drugs. It identified PARP inhibitor rucaparib and anthracycline doxorubicin as sensitive drugs in HR-deficient patients, and paclitaxel as sensitive in HR-proficient patients. A HRD signature was identified based on gene expression data and a transcriptomic HRD score was constructed to analyze the functional association between anticancer drug perturbation and HRD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Wataru Nakajima, Kai Miyazaki, Masahiro Sakaguchi, Yumi Asano, Mariko Ishibashi, Tomoko Kurita, Hiroki Yamaguchi, Hiroyuki Takei, Nobuyuki Tanaka
Summary: This study found that the combination therapy of decitabine and cisplatin is effective in treating triple-negative breast cancer. Decitabine enhances the proapoptotic effect of cisplatin in cisplatin-resistant breast cancer cells, and it also independently induces cell death in cisplatin-refractory cells.
Article
Biochemistry & Molecular Biology
Lai Wong, Frederick S. Vizeacoumar, Franco J. Vizeacoumar, Linda Chelico
Summary: The study characterizes APOBEC1 and its potential role in cancer, suggesting that RPA may act as a defense against off-target deamination for certain APOBEC enzymes. The data supports a model where the competition between APOBEC and RPA can better predict genomic damage compared to mRNA expression levels and mutation signature analysis in tumors.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Oncology
Kalpana K. Bhanumathy, Amrutha Balagopal, Frederick S. Vizeacoumar, Franco J. Vizeacoumar, Andrew Freywald, Vincenzo Giambra
Summary: Protein phosphorylation is a key regulatory mechanism controlling cellular responses, catalysed by members of the protein kinase superfamily. Tyrosine kinases have been extensively studied for their roles in human malignancies, leading to the development of targeted therapies. Various tyrosine kinases, both receptor and nonreceptor types, play critical roles in the pathogenesis and drug resistance of leukemia, highlighting their potential as therapeutic targets.
Article
Multidisciplinary Sciences
Frederick S. Vizeacoumar, Hongyu Guo, Lynn Dwernychuk, Adnan Zaidi, Andrew Freywald, Fang-Xiang Wu, Franco J. Vizeacoumar, Shahid Ahmed
Summary: This study identified leading differentially expressed genes in GE cancers that can potentially serve as biomarkers. By constructing a co-expression network and performing complex network analysis, the importance of these genes as biomarkers was confirmed.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Thiago Seraphim, Nardin Nano, Yiu Wing Sunny Cheung, Siripat Aluksanasuwan, Carolina Colleti, Yu-Qian Mao, Vaibhav Bhandari, Gavin Young, Larissa Holl, Sadhna Phanse, Yuliya Gordiyenko, Daniel R. Southworth, Carol Robinson, Visith Thongboonkerd, Lisandra M. Gava, Julio C. Borges, Mohan Babu, Leandro R. S. Barbosa, Carlos H. Ramos, Philipp Kukura, Walid A. Houry
Summary: The R2TP complex, formed by RUVBL1 and RUVBL2 ATPases, associates with PIH1D1 and RPAP3 proteins and plays a role in promoting the formation of macromolecular complexes. RPAP3 is identified as the central subunit of R2TP, linking PIH1D1 and RUVBL1/2. The study provides insights into the structure and function of the R2TP complex.
Article
Biochemistry & Molecular Biology
Zahra Sepehri, Archana Banerjee, Frederick S. Vizeacoumar, Andrew Freywald, Franco J. Vizeacoumar, Vernon W. Dolinsky, James R. Davie
Summary: HNF1A-AS1 is a long non-coding RNA expressed in multiple types of cancer and associated with poor clinical prognosis and oncogenic properties. This study reveals the epigenetic features of HNF1A gene locus in colorectal cancer cells and suggests that HNF1A-AS1 may contribute to oncogenic properties by interacting with specific proteins and forming RNA-DNA triplexes.
Article
Biochemistry & Molecular Biology
Sang Hyun Lim, Jamie Snider, Liron Birimberg-Schwartz, Wan Ip, Joana C. Serralha, Hugo M. Botelho, Miqueias Lopes-Pacheco, Madalena C. Pinto, Mohamed Taha Moutaoufik, Mara Zilocchi, Onofrio Laselva, Mohsen Esmaeili, Max Kotlyar, Anna Lyakisheva, Priscilla Tang, Lucia Lopez Vazquez, Indira Akula, Farzaneh Aboualizadeh, Victoria Wong, Ingrid Grozavu, Teuta Opacak-Bernardi, Zhong Yao, Meg Mendoza, Mohan Babu, Igor Jurisica, Tanja Gonska, Christine E. Bear, Margarida D. Amaral, Igor Stagljar
Summary: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride and bicarbonate channel that plays a critical role in maintaining fluid homeostasis. Mutations in CFTR are associated with Cystic Fibrosis (CF), the most common lethal autosomal recessive disorder in Caucasians. This study used a high-throughput screening technique to map the protein-protein interactions of CFTR and identify potential drug targets for CF treatment. They discovered candidate proteins, such as FGL2, that may have significant effects on CFTR function in CF pathophysiology.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Virology
Subha Dahal, Ran Cheng, Peter K. Cheung, Terek Been, Ramy Malty, Melissa Geng, Sarah Manianis, Lulzim Shkreta, Shahrazad Jahanshahi, Johanne Toutant, Rose Chan, Sean Park, Mark A. Brockman, Mohan Babu, Samira Mubareka, Karen Mossman, Arinjay Banerjee, Scott Gray-Owen, Martha Brown, Walid A. Houry, Benoit Chabot, David Grierson, Alan Cochrane
Summary: In this study, the medicinal chemistry optimization of a known HIV-1 inhibitor led to the discovery of a new derivative, GPS491, which showed potent anti-HIV-1 activity with reduced toxicity. The study demonstrated that GPS491 not only blocked HIV-1 replication, but also inhibited the replication of adenovirus and multiple coronaviruses. Furthermore, GPS491 induced changes in viral RNA processing and altered the accumulation/phosphorylation/function of splicing regulatory SR proteins. This study highlights the potential of targeting cellular factors involved in RNA processing for the development of broad-spectrum antiviral agents.
Article
Neurosciences
Elisabet Jakova, Mohamed Taha Moutaoufik, Jeremy S. Lee, Mohan Babu, Francisco S. Cayabyab
Summary: This study found that adenosine and A1R receptor ligands interact with alpha-syn to modulate its aggregation and neurodegeneration. A1R agonists and drugs promoting a knot conformation of alpha-syn can cause alpha-synucleinopathy and increase neuronal degeneration, whereas A1R antagonists and drugs promoting a loop conformation of alpha-syn can be harnessed for possible neuroprotective therapies.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Multidisciplinary Sciences
Alla Gagarinova, Ali Hosseinnia, Matineh Rahmatbakhsh, Zoe Istace, Sadhna Phanse, Mohamed Taha Moutaoufik, Mara Zilocchi, Qingzhou Zhang, Hiroyuki Aoki, Matthew Jessulat, Sunyoung Kim, Khaled A. Aly, Mohan Babu
Summary: By studying genetic interactions among all transcription factor genes in E. coli, this research reveals condition-dependent interactions and uncovers the roles of uncharacterized transcription factors.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Hussain Elhasasna, Raymond Khan, Kalpana K. Bhanumathy, Frederick S. Vizeacoumar, Prachi Walke, Maricris Bautista, Dinesh K. Dahiya, Vincent Maranda, Hardikkumar Patel, Amrutha Balagopal, Nezeka Alli, Anand Krishnan, Andrew Freywald, Franco J. Vizeacoumar
Summary: Neuroendocrine prostate cancer (NEPC) is a highly aggressive form of prostate tumors and often occurs as an adaptive response to androgen deprivation therapy. Overexpression of MYCN oncogene and loss of TP53 and RB1 activities are associated with NEPC. Fludarabine phosphate has been identified as a drug that can selectively inhibit the proliferation of N-MYC overexpressing NEPC cells by inducing reactive oxygen species (ROS).
Article
Oncology
Terra G. Arnason, Valerie MacDonald-Dickinson, Matthew Casey Gaunt, Gerald F. Davies, Liubov Lobanova, Brett Trost, Zoe E. Gillespie, Matthew Waldner, Paige Baldwin, Devon Borrowman, Hailey Marwood, Frederick S. Vizeacoumar, Franco J. Vizeacoumar, Christopher H. Eskiw, Anthony Kusalik, Troy A. A. Harkness
Summary: The insulin sensitizer, metformin, reduces drug resistance markers in canines with lymphoma and activates the Anaphase Promoting Complex (APC), suggesting its potential as a treatment for multiple drug resistant cancers. Cell lines selected for resistance to chemotherapeutic drugs showed that APC activation restored chemosensitivity and improved survival. These findings provide insights into the mechanisms of multiple drug resistance and suggest a potential therapeutic strategy for overcoming drug resistance in cancer.
Review
Biochemistry & Molecular Biology
Khaled A. Aly, Mohamed Taha Moutaoufik, Mara Zilocchi, Sadhna Phanse, Mohan Babu
Summary: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare early-onset neurodegenerative disease caused by mutations in the SACS gene. Understanding the function of Sacsin and using ARSACS disease models can improve our knowledge of this disease. Gene correction strategies and delivery methods provide hope for the development of therapeutics for ARSACS.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Oncology
Amr El Zawily, Frederick S. Vizeacoumar, Renuka Dahiya, Sara L. Banerjee, Kalpana K. Bhanumathy, Hussain Elhasasna, Glinton Hanover, Jessica C. Sharpe, Malkon G. Sanchez, Paul Greidanus, R. Greg Stacey, Kyung-Mee Moon, Ilya Alexandrov, Juha P. Himanen, Dimitar B. Nikolov, Humphrey Fonge, Aaron P. White, Leonard J. Foster, Bingcheng Wang, Behzad M. Toosi, Nicolas Bisson, Tajib A. Mirzabekov, Franco J. Vizeacoumar, Andrew Freywald
Summary: This study presents and validates a multipronged unbiased strategy for predicting optimal co-targets for bispecific therapeutics. EGFR and EPHA2 tyrosine kinase receptors are identified as the best fit co-targets for multiple tumor types. Furthermore, a new bispecific anti-EGFR/EPHA2 antibody is developed and shown to effectively suppress tumor growth compared to existing therapeutic antibodies.
CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Glinton Hanover, Frederick S. Vizeacoumar, Sara L. Banerjee, Raveena Nair, Renuka Dahiya, Ana I. Osornio-Hernandez, Alain Morejon Morales, Tanya Freywald, Juha P. Himanen, Behzad M. Toosi, Nicolas Bisson, Franco J. Vizeacoumar, Andrew Freywald
Summary: Eph receptors and ephrin ligands are considered promising targets for cancer treatment. However, their context-dependent functionalities hinder the targeting approach. To overcome this, we investigate the molecular landscapes of Ephs and ephrins and construct a cancer-related network of genetic interactions (GIs) to aid therapeutic manipulation. Our study highlights the involvement of EPHB6 in EGFR signaling and suggests the potential benefit of targeting EPHB6 in EGFR-dependent tumors.
Article
Chemistry, Analytical
Premkumari Kumarathasan, Nazila Nazemof, Dalibor Breznan, Erica Blais, Hiroyuki Aoki, James Gomes, Renaud Vincent, Sadhna Phanse, Mohan Babu
Summary: This study evaluated the internalization and mitochondrial effects of silica nanoparticles (SiNPs) with different sizes and surface modifications. The findings suggest that physicochemical properties are determinants of SiNP exposure-related mitochondrial effects. Mitochondrial exposures combined with proteomic analysis can serve as a new approach in risk assessment, providing insights into related toxicity mechanisms.