Article
Oncology
Michael W. Lewis, Kamila Wisniewska, Caitlin M. King, Shen Li, Alisha Coffey, Michael R. Kelly, Matthew J. Regner, Hector L. Franco
Summary: In this study, a novel enhancer that specifically activates the oncogene CSF1 in triple-negative breast cancer patients was identified. Using CRISPR-based genome engineering techniques, the researchers systematically perturbed the enhancer to understand its mechanisms of action and its impact on tumor cell growth. The study also demonstrated that the enhancer function model could be applied to other cancer types. These findings highlight the significant impact of enhancers in cancer biology and suggest their potential as targets for therapeutic intervention.
Article
Cell Biology
Stella C. Ogbu, Samuel Rojas, John Weaver, Phillip R. Musich, Jinyu Zhang, Zhi Q. Yao, Yong Jiang
Summary: Breast cancer is a prevalent cancer in women, and therapeutic resistance to chemotherapy is a major challenge in improving the treatment outcomes. A protein kinase called DSTYK has been found to play a crucial role in promoting chemoresistance in breast cancer cells, particularly in triple-negative breast cancer. This discovery provides valuable insights and lays the foundation for developing new strategies targeting DSTYK to enhance the efficacy of TNBC therapy.
Article
Oncology
Qiqi Mao, Peibin Wu, Haochen Li, Xiaolan Fu, Xuechen Gao, Lei Yang
Summary: The study demonstrated that knocking out the EZH2 gene using the CRISPR/Cas9 system resulted in significant decrease in proliferation and migration ability of TNBC cells. These findings suggest that EZH2 plays a key role in the development of TNBC.
Article
Oncology
Craig A. Vincent, Itzel Nissen, Soran Dakhel, Andreas Hornblad, Silvia Remeseiro
Summary: This study demonstrates how epigenomic perturbation of EGFR enhancers can ameliorate the aggressiveness of glioblastoma cells and enhance the efficacy of TMZ treatment. CRISPR/Cas9-based perturbation of enhancers can be used to modulate the expression of key cancer genes, which can help improve the effectiveness of existing cancer treatments and potentially the prognosis of difficult-to-treat cancers such as glioblastoma.
Review
Biochemistry & Molecular Biology
Takuya Tsujino, Kazumasa Komura, Teruo Inamoto, Haruhito Azuma
Summary: In recent years, advances in omics technology and CRISPR/Cas9 technology have improved the identification of genes associated with cancer diseases, providing opportunities for the discovery of new therapeutic targets. This knowledge plays a crucial role in clinicians' decision-making regarding patient treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Genetics & Heredity
Munazza Ahmed, Grace Hope Daoud, Asmaa Mohamed, Rania Harati
Summary: Breast cancer is a prevalent and heterogeneous disease with complex pathogenesis, often treated by alleviating symptoms rather than targeting mutations. CRISPR/Cas9 is a groundbreaking gene-editing tool that offers a promising new approach for the treatment of breast cancer, surpassing previous methods in terms of simplicity, efficiency, and affordability.
Article
Biochemistry & Molecular Biology
Uijin Kim, Suyeon Kim, Nahyun Kim, Ha Youn Shin
Summary: The activation of mammary-specific super-enhancers relies on protein-protein interactions between mammary-enriched transcription factors, and ELF5 and STAT5A play key roles in the activation of the super-enhancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Juhee Lee, Yoo Kyung Kang, Eonju Oh, Juhee Jeong, San Hae Im, Duk Ki Kim, Haeshin Lee, Sang-Gyu Kim, Keehoon Jung, Hyun Jung Chung
Summary: The study presents a cancer gene therapy strategy based on NanoRNP that efficiently blocks the PD-L1 immune checkpoint and induces an antitumor effect in vivo without the need for combination therapy. In vivo results demonstrate that NanoRNP can induce indels in target cells at high frequencies, significantly suppressing tumor growth.
CHEMISTRY OF MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Xu Han, Minghui Li, Jin Xu, Jingyue Fu, Xinyang Wang, Jingyi Wang, Tiansong Xia, Shui Wang, Ge Ma
Summary: This study found that the expression level of miR-1275 is decreased in chemoresistant breast cancer, and low levels of miR-1275 are associated with poor overall survival. Knocking out miR-1275 increases chemoresistance in breast cancer cells by increasing cancer stem cell properties. miR-1275 could serve as a prognostic biomarker and therapeutic target for breast cancer patients.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shiro Uchida, Takashi Sugino
Summary: This study identified genes associated with breast cancer progression mechanisms and potential therapeutic targets using bioinformatic tools. It found several genes involved in breast cancer progression and identified potential novel therapeutic targets.
Article
Pharmacology & Pharmacy
Ruru Gao, Qiong Luo, Yang Li, Liming Song, Junnan (Stephen) Cai, Ying Xiong, Fei Yan, Jianhua Liu
Summary: This study demonstrated a novel strategy using ultrasound combined with biosynthetic nanobubbles (Gas Vesicles, GVs) to knock out the EMT-related Cdh2 gene through CRISPR/Cas9 gene editing, effectively inhibiting tumor invasion and metastasis.
Article
Biochemistry & Molecular Biology
Chaya T. L. Yuen, Dawn G. L. Thean, Becky K. C. Chan, Peng Zhou, Cynthia C. S. Kwok, Hoi Yee Chu, Maggie S. H. Cheung, Bei Wang, Yee Man Chan, Silvia Y. L. Mak, Anskar Y. Leung, Gigi C. G. Choi, Zongli Zheng, Alan S. L. Wong
Summary: Researchers have enhanced editing accuracy and reduced off-target edits by re-engineering KKH-SaCas9 with a Y239H mutation and a set of additional mutations, demonstrating the feasibility of multi-domain combinatorial mutagenesis to optimize editing fidelity.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Oncology
Vamika Karn, Sandhya Sandhya, Wayne Hsu, Deepak Parashar, Himanshu Narayan Singh, Niraj Kumar Jha, Saurabh Gupta, Navneet Kumar Dubey, Sanjay Kumar
Summary: Cancer is a major cause of death globally, with breast cancer being the most common type affecting women worldwide. Various treatment strategies, including gene therapy using CRISPR/Cas9, are being explored to improve outcomes for breast cancer patients by targeting drug resistance and enhancing immunotherapy.
CANCER CELL INTERNATIONAL
(2022)
Article
Engineering, Biomedical
Jabeen Farheen, Narayan S. Hosmane, Ruibo Zhao, Qingwei Zhao, M. Zubair Iqbal, Xiangdong Kong
Summary: This review provides an overview of the genetic mechanisms, available treatments, and gene therapies for TNBC, as well as the application and recent advances of CRISPR-nano complex in TNBC. However, challenges still remain in delivery, biodegradability, and toxicity of CRISPR-nano complex.
MATERIALS TODAY BIO
(2022)
Article
Biology
Keity J. Farfan-Pira, Teresa I. Martinez-Cuevas, Timothy A. Evans, Marcos Nahmad
Summary: The scaling relationship between wing and fore tibia lengths differs among different species of fruit flies. D. virilis has smaller wings relative to their body size compared to other species. By using CRISPR/Cas9 technology, it was discovered that a specific cis-regulatory element in D. virilis contributes to constraining wing size in this species, supporting the hypothesis that scaling could evolve through genetic variations in cis-regulatory elements.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anna G. Manjon, Simon Linder, Hans Teunissen, Anoek Friskes, Wilbert Zwart, Elzo de Wit, Rene H. Medema
Summary: CRISPR has revolutionized molecular biology as a genome editing tool. However, lentiviral-based sgRNA vectors may integrate into the endogenous genomic target location, leading to undesired activation of the target gene and potential drug resistance. Further research is needed to understand and address this unreported CRISPR/Cas9 on-target effect.
Review
Oncology
Hande Ozkan, Deniz Gulfem Ozturk, Gozde Korkmaz
Summary: Transcriptional regulation of breast cancer tumorigenesis has been studied primarily in 2D culture models, but 3D cell culture models better mimic the in vivo tumor microenvironment and have great potential for breast cancer research.
Review
Genetics & Heredity
Julien Champagne, Kelly Mordente, Remco Nagel, Reuven Agami
Summary: Programmed ribosomal frameshifting (PRF) is a crucial mechanism used by viruses to replicate and regulate gene expression. Recent studies have found that ribosomes in many types of human cancer cells are prone to frameshifting under amino acid shortage, resulting in the production of aberrant proteins that may trigger T cell activation.
TRENDS IN GENETICS
(2022)
Review
Oncology
Remco Nagel, Abhijeet Pataskar, Julien Champagne, Reuven Agami
Summary: Immune-checkpoint blockade therapy has shown success in treating cancers with high mutational burden and abundant neoantigens. However, tumors lacking classic genetically derived neoantigens require novel approaches to enhance immunotherapy efficacy. Recent discoveries of non-genetically encoded and inducible neoepitopes offer new avenues for therapeutic development to improve sensitivity to immunotherapies.
Article
Biochemistry & Molecular Biology
Sebastian M. Dieter, Domenica Lovecchio, Abhijeet Pataskar, Martina K. Zowada, Pierre-Rene Korner, Anna Khalizieva, Olaf van Tellingen, Dirk Jaeger, Hanno Glimm, Reuven Agami
Summary: Accumulating evidence suggests that non-genetic mechanisms play a substantial role in drug resistance in cancer patients. This study identifies the transcriptional co-activators YAP1 and TAZ as important contributors to resistance to targeted therapies. By using a genome-wide CRISPR/Cas9 functional screen, the study identifies SLC35B2 as an essential gene for YAP1/TAZ-driven drug resistance. Inhibition of SLC35B2 sensitizes resistant melanoma cells to BRAF inhibition, providing a potential therapeutic strategy to overcome resistance.
Review
Biochemistry & Molecular Biology
Adva Kochavi, Domenica Lovecchio, William James Faller, Reuven Agami
Summary: mRNA translation is altered in cancer to promote cancer development and can be targeted for immunotherapy. Ribosome heterogeneity and alternative responses to nutrient shortages in cancer cells may result in therapeutic targets such as cancer-specific peptides. This review will assess the underlying mechanisms of proteome diversification in cancer cells due to alterations in mRNA translation.
Article
Multidisciplinary Sciences
Olimpia Alessandra Buoninfante, Bas Pilzecker, Aldo Spanjaard, Daniel de Groot, Stefan Prekovic, Ji-Ying Song, Cor Lieftink, Matilda Ayidah, Colin E. J. Pritchard, Judith Vivie, Kathleen E. Mcgrath, Ivo J. Huijbers, Sjaak Philipsen, Marieke von Lindern, Wilbert Zwart, Roderick L. Beijersbergen, James Palish, Paul C. M. van den Berk, Heinz Jacobs
Summary: DNA damage poses a threat to genomic integrity and leads to stem cell failure. Cells use DNA damage tolerance (DDT), regulated by PCNA ubiquitination and REV1, to bypass genotoxic lesions during replication. While DDT is conserved in all domains of life, its relevance in mammals has been unclear. Our study demonstrates that inactivation of both PCNA ubiquitination and REV1 results in embryonic and adult lethality, as well as accumulation of DNA damage in hematopoietic stem and progenitor cells (HSPCs) which ultimately leads to their depletion. This highlights the crucial importance of DDT in the maintenance of stem cell compartments and mammalian life under unperturbed conditions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Jeroen Kneppers, Tesa M. Severson, Joseph C. Siefert, Pieter Schol, Stacey E. P. Joosten, Ivan Pak Lok Yu, Chia-Chi Flora Huang, Tunc Morova, Umut Berkay Altintas, Claudia Giambartolomei, Ji-Heui Seo, Sylvan C. Baca, Isa Carneiro, Eldon Emberly, Bogdan Pasaniuc, Carmen Jeronimo, Rui Henrique, Matthew L. Freedman, Lodewyk F. A. Wessels, Nathan A. Lack, Andries M. Bergman, Wilbert Zwart
Summary: The chromatin binding of androgen receptor (AR) exhibits high heterogeneity in primary prostate tumors, which overlaps with the heterogeneity observed in healthy prostate epithelium. This heterogeneity has functional consequences, as somatic mutations occur commonly at AR sites that are shared in primary, but not metastatic tissues. Additionally, less frequently shared AR sites are strongly associated with AR-driven gene expression and can also differentiate patient outcomes.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Abhijeet Pataskar, Jasmine Montenegro Navarro, Reuven Agami
Summary: ABPEPserver is an online database and analytical platform that visualizes a large-scale tumor proteomics analysis of Substitutant expression across eight tumor types sourced from the CPTAC database. It offers gene-association signature analysis of Substitutant peptides, comparison of enrichment between tumor and tumor-adjacent normal tissues, and a list of candidate peptides for immunotherapy design.
Article
Oncology
Floriane Racine, Christophe Louandre, Corinne Godin, Baptiste Chatelain, Stefan Prekovic, Wilbert Zwart, Antoine Galmiche, Zuzana Saidak
Summary: Human tumors often exhibit a hypercoagulant state that promotes vascular complications. The tumor coagulome, a repertoire of tumor-expressed genes that regulates coagulation and fibrinolysis, has been found to be linked with the tumor microenvironment. Glucocorticoids were discovered to regulate the coagulome through direct transcriptional and indirect effects, which have potential vascular consequences and impact on the tumor microenvironment.
Article
Biochemistry & Molecular Biology
Dorien Clarisse, Stefan Prekovic, Philip Vlummens, Eleni Staessens, Karlien Van Wesemael, Jonathan Thommis, Daria Fijalkowska, Guillaume Acke, Wilbert Zwart, Ilse M. Beck, Fritz Offner, Karolien De Bosscher
Summary: The interaction between glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) improves drug efficacy in multiple myeloma. Co-treatment of the GR agonist dexamethasone (Dex) with the MR antagonist spironolactone (Spi) enhances cell killing in myeloma, and this combination treatment affects the expression of prognosis-related genes and proteins in myeloma patients.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Oncology
Stefan Prekovic, Wilbert Zwart
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Selcuk Yavuz, Helene Kabbech, Jente van Staalduinen, Simon Linder, Wiggert A. van Cappellen, Alex L. Nigg, Tsion E. Abraham, Johan A. Slotman, Marti Quevedo, Raymond A. Poot, Wilbert Zwart, Martin E. van Royen, Frank G. Grosveld, Ihor Smal, Adriaan B. Houtsmuller
Summary: This study reveals the formation of visible foci of androgen receptors (ARs) in the nucleus upon stimulation by testosterone, as well as the potential compartmentalization of these foci through liquid-liquid phase separation. Furthermore, it demonstrates the presence of AR-regulated genes within these foci.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biology
Seham Elabd, Eleonora Pauletto, Valeria Solozobova, Nils Eickhoff, Nuno Padrao, Wilbert Zwart, Christine Blattner
Summary: TRIM25 targets p300 for degradation by promoting its interaction with dynein, leading to the regulation of p300-dependent gene expression.
LIFE SCIENCE ALLIANCE
(2023)
Review
Endocrinology & Metabolism
Nils Eickhoff, Andries M. Bergman, Wilbert Zwart
Summary: Recent studies have revealed that the androgen receptor (AR) in prostate cancer models and patient samples exhibits high plasticity, with associations to specific mutations and protein interactions. This has important implications for identifying therapeutic targets to prevent the emergence of treatment resistance.
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.